用户名: 密码: 验证码:
Smad信号转导通路相关基因表达与湖羊高繁殖力关系的研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
湖羊是世界著名的多胎绵羊品种,Smad信号通路中的很多信号分子与绵羊的生殖和卵泡发育有密切关系,参与调控绵羊排卵数、产羔数等多胎性状,为了探讨湖羊多胎与Smad信号通路的关系,我们利用RT-PCR技术首次系统检测了Smad信号通路中相关信号分子基因的组织表达谱,并进一步利用实时荧光定量PCR的方法研究了繁殖力较低湖羊(经产单羔:单羔组)和繁殖力较高湖羊(经产三、四羔:多羔组)与Smad信号转导通路相关基因在垂体和卵巢组织以及有腔卵泡中的表达差异,并分析了Smad言号通路中的有关基因表达量与排卵数的相关性。我们的研究结果提供了Smad言号通路有关基因在mRNA表达水平对湖羊排卵数的可能调控机理,同时为揭示湖羊高繁多胎机理和筛选影响湖羊多胎性状的特有候选基因提供了参考。
     1.湖羊BMP/Smad言号通路相关基因组织表达特征
     用RT-PCR法检测湖羊BMP/Smad信号通路中信号分子基因组织表达特征,结果成功克隆得到了BMP/Smad信号通路中BMP2、BMP4、BMP6、BMP7、BMP15、BMPRIA、BMPRIB、BMPRII、Smad1、Smad5、Smad4等信号分子基因部分cDNA片段,组织表达谱研究表明,BMP2、BMP4、BMP7、BMPRII、BMPRIA、BMPRIB、Smad1知Smad4基因在成年发情期湖羊母羊下丘脑、垂体、卵巢、子宫、输卵管、心脏、肝脏、脾脏、肺脏、肾脏、肌肉组织中均有表达,而BMP6基因仅在成年湖羊母羊卵巢、输卵管、’肾脏、肌肉组织中有表达;Smad5在子宫、输卵管、肺脏和肌肉组织中没有表达;BMP15仅在卵巢组织表达,为卵巢组织特异表达基因。从结果看,BMP/Smad信号转导通路相关基因mRNA表达与湖羊垂体和卵巢功能可能有密切联系
     2.高、低产湖羊垂体组织BMP/Smad信号通路分子基因表达差异及与排卵数相关性的研究
     我们首次利用荧光定量PCR技术对湖羊BMP/Smad信号通路中信号分子基因(包括BMP蛋白家族基因BMP2、BMP4、BMP7; BMP受体基因BMPRIA、BMPRIB、BMPRII;细胞内Smad蛋白家族基因Smadl、Smad4、Smad5) mRNA在高繁殖力(经产三、四羔:多羔组)和低繁殖力(经产单羔:单羔组)湖羊母羊发情后24-36小时排卵时期在垂体组织中的表达水平进行分析。结果显示,多羔组卵巢排卵数极显著高于单羔组(P<0.01);在垂体组织中,BMP2、BMP7、BMPRIA、BMPRII.Smadl知Smad4基因表达量在单羔组和多羔组垂体组织内没有显著差异(P>0.05),但是,多羔组BMP4、BMPRIB知Smad5基因表达量极显著低于单羔组(P<0.01),且与卵巢排卵数均分别呈不同程度的负相关(P<0.05或P<0.01),说明湖羊垂体组织BMP4.BMPRIB知Smad5基因表达量差异可能是引起湖羊较高产羔数的原因之一。
     3.高、低产湖羊卵巢组织BMP/Smad信号通路分子基因表达差异及与排卵数相关性的研究
     我们利用荧光定量PCR技术分析了高繁殖力(经产三、四羔:多羔组)和低繁殖力(经产单羔:单羔组)湖羊母羊发情后24-36小时排卵时期卵巢组织中BMP/Smad通路中的BMP蛋白家族基因(BMP2、BMP4、BMP6、BMP7\BMP15), BMP受体基因(BMPRIA、BMPRIB、BMPRII)和细胞内Smad蛋白家族基因(Smadl、Smad5, Smad4)表达水平差异及其与卵巢排卵数间的相关性,结果显示:多羔组湖羊BMP4、BMPRIB知Smad4基因mRNA表达极显著高于单羔组(P<0.01),BMP15知BMPRII基因mRNA表达显著高于单羔组(P<0.05),而BMP2、BMP6、BMP7、BMPRIA、Smadl知Smad5基因mRNA表达在单羔组和多羔组间没有显著差异(P>0.05);相关分析表明卵巢组织中BMP4、BMP15、BMPRIB、BMPRII、Smad5和Smad4基因mRNA表达与排卵数呈正相关,表明BMP4、BMP15、BMPRIB、BMPRII知Smad4基因在mRNA水平对湖羊排卵数有影响,可能是影响湖羊高产、多胎性状的候选基因。
     4.不同繁殖力湖羊有腔卵泡BMP/Smad信号通路基因表达水平研究
     为了进一步探讨湖羊多胎与BMP/Smad信号通路的关系,我们以机械法获取高繁殖力(经产三、四羔:多羔组)和低繁殖力(经产单羔:单羔组)湖羊母羊发情后24-36小时排卵时期卵巢组织中的部分有腔卵泡,利用荧光定量PCR技术对BMP/Smad信号通路基因(包括BMP蛋白家族基因BMP2、BMP4、BMP6、BMP7、BMP15; BMP受体基因BMPRIA、BMPRIB、BMPRII;细胞内Smad蛋白家族基因Smadl、Smad4、Smad5) mRNA在有腔卵泡中的表达水平进行分析,结果显示:多羔组湖羊BMP4,BMPRIB和BMPRIl基因mRNA表达显著高于单羔组(P<0.05), Smad4基因mRNA表达极显著高于单羔组(P<0.01), BMP15 mRNA显著低于单羔组(P<0.05), BMP2、BMP6、BMP7、BMPRIA、Smad1知Smad5基因mRNA表达在单羔组和多羔组湖羊有腔卵泡中的表达没有显著差异(P>0.05)。结果提示单羔组和多羔组湖羊BMP4、BMP15、BMPRIB、BMPRIⅠ和Smad4基因表达差异可能是湖羊多胎原因之一。
     5.湖羊TGF-β/Smad言号通路相关基因组织表达特征
     用RT-PCR法检测湖羊TGF-β/Smad信号通路中信号分子基因组织表达特征,结果成功克隆得到了TGF-β/Smad信号通路中TGF-β1、TGF-β2、TGF-β3、TGF-βRⅠ、TGF-βRⅡ、Smad2、Smad7等信号分子基因部分cDNA片段,组织表达谱研究表明,TGF-β1、TGF-β2、TGF-β3、TGF-βRⅠ、TGF-βRⅡ、Smad2知Smad7在湖羊母羊卵巢、子宫、输卵管等生殖器官有表达外,在下丘脑、垂体、心脏、肝脏、脾脏、肾脏、肌肉组织中也均有表达,但是TGF-β1、TGF-β2、TGF-β3、TGF-βRⅠ在肺脏组织中没有表达,而TGF-βRⅡ、Smad2知Smad7在肺脏中有表达。从结果看,TGF-β/Smad信号通路相关基因在湖羊体内广泛表达,而在卵巢组织均可检测到其明显表达,说明TGF-β/Smad信号通路相关基因对湖羊繁殖功能可能有一定的影响。
     6.高、低产湖羊卵巢组织TGF-β/Smad信号通路分子基因表达差异及与排卵数相关性的研究
     对高繁殖力(经产三、四羔:多羔组)和低繁殖力(经产单羔:单羔组)湖羊母羊发情后24-36小时卵巢组织中TGF-β/Smad信号通路的TGF-β蛋白基因(TGF-β1、TGF-β2、TGF-β3), TGF-P受体基因(TGF-βRⅠ知TGF-βRⅡ)和细胞内Smad蛋白家族基因(Smad2、Smad7)在卵巢组织的表达水平及其与卵巢排卵数间的相关性进行研究,发现多羔组湖羊卵巢组织TGF-β1知TGF-β2基因表达显著高于单羔组(P<0.05), TGF-β3、TGF-βRⅡ知TGF-βRⅠ基因表达极显著高于单羔组(P<0.01);Smad7基因表达则显著低于单羔组(P<0.01);Smaad2基因在多羔组和单羔组卵巢组织间没有显著差异(P>0.05)。进一步的相关分析结果表明TGF-β1、TGF-β2、TGF-β3知TGF-βRⅠ与排卵数无相关,TGF-βRⅡ与卵巢排卵数存在显著正相关(P<0.05),Smad7与卵巢排卵数存在显著负相关(P<0.01)。表明TGF-PRⅡ和Smad7基因在mRNA水平对湖羊排卵数有影响,可能是影响湖羊高产、多胎性状的候选基因。
Hu sheep is famous for its hyper-prolificacy in the world, and the members of Smad pathway are shown to have close relationships with reproduction and follicular development with roles of regulating ovulation and litter size in sheep. In order to investigate the mechanism of high fecundity in Hu sheep and its relationships with Smad pathway, tissue mRNA distributions of genes encoding Smad pathway molecules were detected by RT-PCR, and the differential expression levels in ovaries, pituitaries and antral follicles of high-fecundity (HF) and low-fecundity (LF) Hu sheep were further investigated by real-time PCR. In addition, SPSS software was used to analyze the relationship between the gene expression level and ovulation number in Hu sheep. Our data show the first evidence that genes of Smad pathway in the mRNA levels may be correlated with regulation of ovulation number in Hu sheep and provide the reference for finding candidate genes of high fecundity and understanding the molecular mechanism of hyper-prolificacy in Hu sheep.
     1. Tissue Expression Profiles of BMP/Smad Pathway Molecule Gene mRNAs in Hu Sheep
     Tissue expression profiles of BMP/Smad pathway molecule gene mRNAs in Hu sheep were detected using RT-PCR. The results showed that cDNA fragments were successfully cloned at expected sizes for genes encoding BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP 15), BMP receptors (BMPRIA, BMPRIB and BMPRII) and intracellular transducers (Smadl, Smad 4, Smad 5 and Smad 7), and tissue mRNA distributions indicated that BMP2, BMP4, BMP7, BMPRIA, BMPRII, Smadl, Smad4 and Smad7 mRNA exited in the ovary and other tissues, including hypothalamus, pituitary, uterus, heart, liver, spleen, lung, kidney, muscle and oviduct, but BMP6 mRNA was only detected in the ovary, kidney, muscle and oviduct, and Smad5 mRNA in uterus, lung, muscle and oviduct were not detected, but BMP15 mRNA was only found in the ovary.lt is suggested that BMP/Smad pathway might have roles in pituitary-ovary axis for prolificacy of Hu sheep.
     2. BMP/Smad Pathway Gene Expression Levels in Pituitaries and Associations with Ovulation Number in Hu Sheep
     The present study was performed to determine the expressional differences of mRNAs encoding BMP/Smad pathway molecules, including BMP2, BMP4, BMP7, BMPRIA,BMPRIB, BMPRII, Smadl, Smad5 and Smad4 in pituitaries of Hu sheep during 24 and 36 hours after estrus diagnosis between high-fecundity (HF) and low-fecundity (LF) and to further investigate the relationships between their expressions and ovulation number. The results showed that there were no significant differences in BMP2,BMP7, BMPRIA,BMPRII,Smadl and Smad4 mRNA abundance in the pituitary between HF and LF group (P>0.05) respectively. But BMP4, BMPRIB and Smad5 mRNA abundances in the pituitary were respectively higher in HF group than those in LF group (P<0.01) and negatively correlated with ovulation number. It is suggested that the expressional differences of BMP4, BMPRIB and Smad5 in the pituitary between high-fecundity and low-fecundity group might be one of factors for high fecundity in Hu sheep.
     3. BMP/Smad Pathway Gene Expression Levels in Ovaries and Associations with Ovulation Number in Hu Sheep
     The mRNA transcript expression differences for members of the BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP 15), BMP receptors (BMPRIA, BMPRIB and BMPRII) and intracellular transducers (Smadl, Smad5 and Smad4) in the ovary of High- fecundity(HF group,) and Low-fecundity (LF) Hu Sheep between 24 and 36 hours after estrus diagnosis were measured by real-time PCR. The results showed that BMP4, BMP15, BMPRIB, BMPRII and Smad4 mRNA abundances in the ovary of HF group were respectively higher than those in LF group (P<0.05 or P <0.01) and also correlated with ovulation number(P<0.05 or P<0.01). But there were no significant differences in BMP2, BMP6, BMP7, BMPRIA, Smadl and Smad5 mRNA abundances in the ovary between LF and HF group (P>0.05). It is suggested that BMP4、BMP15、BMPRIB、BMPRII and Smad4 might play roles in ovulation number and might be candidate genes for high fecundity in Hu sheep. These findings may help to improve the molecular breeding of Hu sheep.
     4.Differential Expression of mRNAs Encoding BMP/Smad Pathway Molecules in Antral Follicles of High-and Low-fecundity Hu Sheep
     In order to further investigate the mechanism of high fecundity in Hu sheep and its relationship with the BMP/Smad pathway, antral follicles were punctured for high-fecundity (HF) and low-fecundity (LF) animals. The gene expression levels of mRNAs encoding BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP15), BMP receptors (BMPRIA, BMPRIB and BMPRⅡ) and intracellular transducers (Smad1, Smad5 and Smad4) in antral follicles were detected by real-time PCR. The results showed that BMP4, BMPRIB, BMPRⅡand Smad4 mRNAs were more abundant in the antral follicles of HF animals than those of LF animals (P<0.05 or P<0.01), but BMP15 mRNA was less abundant (P<0.05).The expression levels of BMP2, BMP6, BMP7, BMPRIA, Smad1 and Smad5 did not differ between the HF and LF groups (P>0.05).This suggests that the expressional differences of BMP4, BMP 15, BMPRIB, BMPRⅡand Smad4 in the antral follicles between high-fecundity and low-fecundity group might be one of factors for high fecundity in Hu sheep.
     5. Tissue Expression Profiles of TGF-β/Smad Pathway Molecule Gene mRNAs in Hu Sheep
     Tissue expression profiles of TGFβ/Smad pathway molecule gene mRNAs encoding TGF-β1,TGF-β2,TGF-β3,TGF-βRⅠ,TGF-βRⅡ,Smad2 and Smad7 in Hu sheep were detected using RT-PCR. The results showed that cDNA fragments were successfully cloned at expected sizes for the genes and tissue mRNA distributions indicated that TGF-β1, TGF-β2,TGF-β3,TGF-βRⅠ,TGF-βRⅡ,Smad2 and Smad7 mRNA exited in the ovary and other tissues, including hypothalamus, pituitary, uterus, heart, liver, spleen, kidney, muscle and oviduct, and TGF-β1, TGF-β2,TGF-β3 and TGF-βRⅠmRNA were not only detected in the lung, but TGF-βRⅡ,Smad2 and Smad7 mRNA exited in lung. It is suggested that genes related toTGF-β/Smad pathway expressed extensively in Hu sheep and the obvious existences of their mRNAs in the ovary might play roles in the ovary for prolificacy in Hu sheep.
     6. TGF-β/Smad Pathway Gene Expression Levels in Ovaries and Associations with Ovulation Number in Hu Sheep
     The mRNA transcript expression differences for members of the TGFβ/Smad pathway molecules including TGF-β1、TGF-β2、TGF-β3 and their receptors (TGF-βRⅠand TGF-βRⅡ) and intracellular transducers (Smad2 and Smad7) in the ovary of High-fecundity(HF) and Low-fecundity (LF) Hu Sheep between 24 and 36 hours after estrus diagnosis were measured by real-time PCR. The results showed that TGF-β1,TGF-β2, TGF-β3,TGF-βRⅠand TGF-βRⅡmRNA abundances in the ovary of HF group were respectively higher but Smad7 was lower than LF group (P<0.05 or P<0.01), and there were no significant differences in Smad2 mRNA abundances in the ovary between HF and LF group (P>0.05), and the correlation analysis also indicated that TGF-βRⅡpositively and Smad7 negatively correlated with ovulation number(P<0.05 and P<0.01). It is suggested that TGF-βRⅡand Smad7 might play roles in ovulation number and might be candidate genes for high fecundity in Hu sheep.These findings may help to improve the molecular breeding of Hu sheep.
引文
[1]李祥龙,张增利,巩元芳,等.我国主要地方绵羊品种遗传亲缘关系[J].中国兽医学报,2004,24(5):508-511.
    [2]李群.湖羊的来源及历史再探[J].中国农史,1997,16(02):91-95.
    [3]陈玲,孙炜,孙永明,等.湖羊的养殖技术[J].农村养殖技术,2006,(17):7-9.
    [4]中国家畜家禽品种志编委会.中国羊品种志[M].上海:上海利学技术出版社,1988.
    [5]徐宁迎,戴旭明,韩玉刚,等.湖羊生长性状遗传参数的估测[J].浙江农业大学学报,1994,20(1):103-105.
    [6]王元兴 闫玉琴,程瑞禾,等.湖羊繁殖力单项选育效果[J].当代畜牧,2000,0(4):31-32.
    [7]徐苏标,程瑞禾.湖羊卵泡及卵母细胞的组织学观测[J].中国养羊,1993,13(1):27-29.
    [8]程瑞禾,张德福,岳根华,等.湖羊与考力代羊生殖器官及卵巢发育的研究[J].浙江农业科学,1993,(5):17-19.
    [9]石国庆.湖羊多胎机制研究[D].南京:南京农业大学博士论文,2006.7.
    [10]Mariana J C, Monniaux D, Caraty A, et al. Immunization of Sheep Against GNRH Early in Life: Effects on Gonadotropins, Follicular Growth and Responsiveness of Granulosa Cells To FSH and IGF-I in Two Breeds of Sheep With Different Prolificacy (Romanov and ILE-DE-France)[J]. Domestic Animal Endocrinology,1998,15(4):195-207.
    [11]J Reyna P C T G E W M C M. Synchrony of Ovulation and Follicular Dynamics in Merino Ewes Treated with GnRH in the Breeding and Non-breeding Seasons[J]. Reproduction in Domestic Animals,2007,42(4):410-417.
    [12]Bartlewski P M, Beard A P, Cook S J, et al. Ovarian antral follicular dynamics and their relationships with endocrine variables throughout the oestrous cycle in breeds of sheep differing in prolificacy[J]. Journal of Reproduction and Fertility,1999,115(1):111-124.
    [13]Xia Y, O'Shea T, Murison R, et al. Concentrations of progesterone, follistatin and follicle stimulating in Merino ewes that are homozygous or non-carriers of the Booroola gene[J]. Biology of Reproduction,2003,69(3):1079-1084.
    [14]Kaulfuss K H, Moritz S, Giucci E. The influence of the ovulation rate on ultrasonically determined ovine corpus luteum morphometry and progesterone concentrations in cyclic and early pregnant sheep[J]. Dtsch Tierarztl Wochenschr,2003,110(6):249-254.
    [15]郑亦辉,张德福.湖羊和美利奴羊多胎遗传差异的内分泌学基础[J].黑龙江畜牧兽医,1992,(8):14.
    [16]张泉福,徐苏标,白莲清,等.湖羊垂体~卵巢轴内分泌与性发育相关研究[J].浙江农业学报,1995,7(5):412-415.
    [17]石国庆,程瑞禾,阎玉琴,等.中国美利奴与湖羊妊娠早期血.清中生殖激素浓度变化的研究[J].草食家畜,2005,126(1):23-25.
    [18]Campbell B K B D T, Souza C J, et al. The FecB (Booroola) gene acts at the ovary:in vivo evidence.[J]. Reproduction,,2003,126(1):101-111.
    [19]谢庄,程瑞禾,韩玉刚.湖羊公羊产羔效应的统计学分析[J].南京农业大学学报,1998,21(1):77-81.
    [20]王元兴,王城,程瑞禾,等.江苏吴县东山湖羊保护区湖羊种质特性及提高措施[J].家畜生态,1998,19(3):26-28.
    [21]刘守仁,邵长发,张凤林,等.美利奴羊(新疆军垦型)多胎品系的选育研究[J].畜牧与兽医,1995,27(6):246-248.
    [22]Mulsant P, Lecerf F, Fabre S, et al. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(9):5104-5109.
    [23]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP 15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [24]Hanrahan J P, Gregan S M, Mulsant P, et al. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP 15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries)[J]. Biology of Reproduction,2004,70(4):900-909.
    [25]Davis G H, Dodds K. G, Wheeler R, et al. Evidence that an imprinted gene on the X chromosome increases ovulation rate in sheep[J]. Biology of Reproduction,2001,64(1):216.
    [26]管峰,艾君涛,刘守仁,等BMPR-IB和BMP15基因作为湖羊多胎性候选基因的研究[J].家畜生态学报,2005,26(3):9-12.
    [27]管峰,刘守仁,程瑞禾,等.绵羊BMP-RIB基因多态性及其与中国美利奴肉用多胎品系产羔数和生长发育的相关性[J].南京农业大学学报,2005,28(2):75-79.
    [28]王根林,毛鑫智,George D,等.DNA分析发现我国湖羊和小尾寒羊存在Booroola (FecB)多胎基因[J].南京农业大学学报,2003,26(1):104-106.
    [29]王启贵,钟发刚,李辉,等.绵羊产羔性状主效基因检测研究[J].遗传,2005,27(1):80-84.
    [30]闫亚东,储明星,曾勇庆,等.小尾寒羊和湖羊高繁殖力候选基因BMPR-IB的研究[J].农业生物技术学报,2005,13(1):66-71.
    [31]储明星,成荣,陈国宏,等.小尾寒羊和湖羊高繁殖力候选基因BMP15的研究[J].安徽农业大学学报,2005,32(3):278-282.
    [32]储明星,桑林华,王金玉,等.小尾寒羊高繁殖力候选基因BMP15和GDF9的研究[J].遗传学报,2005,32(1):38-45.
    [33]储明星,孙洁,陈宏权,等.绵羊BMP15基因FecX-L突变的检测[J].中国农学通报,2007,23(10):85-88.
    [34]管峰,艾君涛,庞训胜,等.绵羊GDF-9和BMP15基因多态性检测[J].生命科学研究,2005,9(2):184-188.
    [35]桑林华,储明星,王金玉,等.绵羊高繁殖力候选基因BMPR-IA的研究[J].畜牧兽医学报, 2006,37(9):852-857.
    [36]刘源,应诗家,祝铁钢,等.湖羊GnRH受体基因的单核苷酸多态性研究[J].江西农业学报,2009,(7):4-8.
    [37]董文艳,陈阿琴,王争光,等.湖羊高繁殖力候选基因ESR的研究[J].浙江农业学报,2009,(6):561-564.
    [38]王凭青,张宝云,储明星,等.绵羊孕酮受体基因的PCR-SSCP分析[J].中国畜牧兽医,2008,(11):24-27.
    [39]李广‘录,赵宗胜,薛安勇,等.湖羊繁殖性状相关候选基因的RFLP分析[J].石河子大学学报(自然科学版),2007,25(6):706-710.
    [40]曾检华,曹少先,舒邓群,等.五个绵羊品种的微卫星位点多样性分析[J].家畜生态学报,2010,(1):25-29.
    [1]杨增明,孙青原,夏国良.生殖生物学[M].北京:科学出版社,2005.
    [2]Kaivo-oja N, Jeffery L A, Ritvos O, et al. Smad signalling in the ovary[J]. Reproductive Biology and Endocrinology,2006,21(4):1-13.
    [3]Drummond A E. TGFβ signalling in the development of ovarian function[J]. Cell and Tissue Research,2005,322(1):107-115.
    [4]Xu R-H, Chen X, Li D S, et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast[J]. Nature Biotechnology,2002,20(12):1261-1264.
    [5]Montesano R, Sarki R, Schramek H. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells[J]. Biochemical and Biophysical Research Communications,2008,374(1):164-168.
    [6]Yang Y-L, Liu Y-S, Chuang L-Y, et al. Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-{beta} Receptors[J]. Endocrinology,2009,150(2):727-740.
    [7]Xiao Y-T, Xiang L-X, Shao J-Z. Bone morphogenetic protein[J]. Biochemical and Biophysical Research Communications,2007,362(3):550-553.
    [8]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP 15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [9]Lan H Y, Mu W, Tomita N, et al. Inhibition of Renal Fibrosis by Gene Transfer of Inducible Smad7 Using Ultrasound-Microbubble System in Rat UUO Model[J]. Journal of the American Society of Nephrology,2003,14(6):1535-1548.
    [10]Massague J, Seoane J, Wotton D. Smad transcription factors[J]. Genes & development,2005, 19(23):2783-2810.
    [11]Wurthner J U, Frank D B, Felici A, et al. Transforming Growth Factor-beta Receptor-associated Protein 1 Is a Smad4 Chaperone[J]. The Journal of Biological Chemistry,2001,276(22): 19495-19502.
    [12]Ishisaki A, Yamato K, Hashimoto S, et al. Differential Inhibition of Smad6 and Smad7 on Bone Morphogenetic Protein- and Activin-mediated Growth Arrest and Apoptosis in B Cells[J]. The Journal of Biological Chemistry,1999,274(19):13637-13642.
    [13]Zhang S, Fei T, Zhang L, et al. Smad7 Antagonizes Transforming Growth Factor{beta} Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation[J]. Molecular and Cellular Biology,2007,27(12):4488-4499.
    [14]Hata A, Lagna G, Massague J, et al. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor[J]. Genes & development,1998,12(2):186-197.
    [15]Goto K, Kamiya Y, Imamura T, et al. Selective Inhibitory Effects of Smad6 on Bone Morphogenetic Protein Type I Receptors[J]. J Biol Chem,2007,282(28):20603-20611.
    [16]Datta P K, Moses H L. STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor beta Signaling[J]. Molecular and Cellular Biology,2000,20(9):3157-3167.
    [17]Shi Y, Massagu J. Mechanisms of TGF-[beta] Signaling from Cell Membrane to the Nucleus[J]. Cell,2003,113(6):685-700.
    [18]Chen X, Rubock M J, Whitman M. A transcriptional partner for MAD proteins in TGF-[beta] signalling[J]. Nature,1996,383(6602):691-696.
    [19]Chen X, Weisberg E, Fridmacher V, et al. Smad4 and FAST-1 in the assembly of activin-responsive factor[J]. Nature,1997,389(6646):85-89.
    [20]Hata A, Seoane J, Lagna G, et al. OAZ Uses Distinct DNA-and Protein-Binding Zinc Fingers in Separate BMP-Smad and Olf Signaling Pathways[J]. Cell,2000,100(2):229-240.
    [21]Chen C-R, Kang Y, Siegel P M, et al. E2F4/5 and p107 as Smad Cofactors Linking the TGF[beta] Receptor to c-myc Repression [J]. Cell,2002,110(1):19-32.
    [22]Steiner A B, Engleka M J, Lu Q, et al. FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development[J]. Development,2006,133(24):4827-4838.
    [23]Pessah M, Prunier C, Marais J, et al. c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(11):6198-6203.
    [24]Zawel L, Le Dai J, Buckhaults P, et al. Human Smad3 and Smad4 Are Sequence-Specific Transcription Activators[J]. Molecular Cell,1998,1(4):611-617.
    [25]Leong G M, Subramaniam N, Figueroa J, et al. Ski-interacting Protein Interacts with Smad Proteins to Augment Transforming Growth Factor-beta -dependent Transcription[J]. The Journal of Biological Chemistry,2001,276(21):18243-18248.
    [26]粉克尔(Finkerl, T.),古金特(Gutkind, J.S.)编,孙超,刘景生等译.信号传导与人类疾病[M].北京:化学工业出版社,2006.
    [27]Chen W, Lam S S, Srinath H, et al. Competition between Ski and CREB-binding protein for binding to Smad proteins in transforming growth factor-beta signaling[J]. The Journal of Biological Chemistry,2007,282(15):11365-11376.
    [28]Knockaert M, Sapkota G, Alarcn C, et al. Unique players in the BMP pathway:Small C-terminal domain phosphatases dephosphorylate Smadl to attenuate BMP signaling[J]. Proceedings of the National Academy of Sciences,2006,103(32):11940-11945.
    [29]Ying Y, Qi X, Zhao G-Q. Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(14):7858-7862.
    [30]Daiji Okamura K H Y M. Mouse epiblasts change responsiveness to BMP4 signal required for PGC formation through functions of extraembryonic ectoderm [J]. Molecular Reproduction and Development,2005,70(1):20-29.
    [31]Ying Y, Zhao G-Q. Cooperation of Endoderm-Derived BMP2 and Extraembryonic Ectoderm-Derived BMP4 in Primordial Germ Cell Generation in the Mouse[J]. Developmental Biology,2001,232(2):484-492.
    [32]Beppu H, Kawabata M, Hamamoto T, et al. BMP Type II Receptor Is Required for Gastrulation and Early Development of Mouse Embryos[J]. Developmental Biology,2000,221(1):249-258.
    [33]de Sousa Lopes S M C, Roelen B A J, Monteiro R M, et al. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo[J]. Genes & development,2004,18(15):1838-1849.
    [34]Hayashi K, Kobayashi T, Umino T, et al. SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast[J]. Mechanisms of Development,2002,118(1-2):99-109.
    [35]Osamu Hashimoto, R. Kelly Moore, Shimasaki S. Posttranslational processing of mouse and human BMP-15:Potential implication in the determination of ovulation quota[J]. Proceedings of the National Academy of Sciences of the United States of America,2005,102(15):5426-5431.
    [36]Chang H, Matzuk M M. Smad5 is required for mouse primordial germ cell development J]. Mechanisms of Development,2001,104(1-2):61-67.
    [37]Sirard C, de la Pompa J L, Elia A, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo[J]. Genes & development, 1998,12(1):107-119.
    [38]Souza C J, Campbell B K, McNeilly A S, et al. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry[J]. Reproduction,2002,123(3):363-369.
    [39]Davis G H, McEwan J C, Fennessy P F, et al. Evidence for the presence of a major gene influencing ovulation rate on the X chromosome of sheep[J]. Biology of Reproduction,1991,44(4): 620-624.
    [40]Galloway S M, Gregan S M, Wilson T, et al. Bmp15 mutations and ovarian function[J]. Mol Cell Endocrinol,2002,191(1):15-18.
    [41]Juengel J L, Hudson N L, Heath D A, et al. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J]. Biology of Reproduction, 2002,67(6):1777-1789.
    [42]Hanrahan J P, Gregan S M, Mulsant P, et al. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP 15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries)[J]. Biology of Reproduction,2004,70(4):900-909.
    [43]Nilsson E E, Skinner M K. Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development J]. Biology of Reproduction,2003,69(4): 1265-1272.
    [44]Tanwar P S, O'Shea T, McFarlane J R. In vivo evidence of role of bone morphogenetic protein-4 in the mouse ovary[J]. Animal Reproduction Science,2008,106(3-4):232-240.
    [45]Pierre A, Pisselet C, Dupont J, et al. Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells[J]. Journal of Molecular Endocrinology, 2004,33(3):805-817.
    [46]Fatehi A N, van den Hurk R, Colenbrander B, et al. Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development[J]. Theriogenology,2005,63(3):872-889.
    [47]Lee W S, Yoon S J, Yoon T K,et al. Effects of Bone Morphogenetic Protein-7 (BMP-7) on Primordial Follicular Growth in the Mouse Ovary[J]. Molecular Reproduction and Development, 2004,69(2):159-163.
    [48]Gilchrist R B, Ritter L J, Myllymaa S, et al. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation[J]. Journal of Cell Science,2006,119(18):3811-3821.
    [49]Juengel J L, Reader K L, Bibby A H, et al. The role of bone morphogenetic proteins 2,4,6 and 7 during ovarian follicular development in sheep:contrast to rat[J]. Reproduction,2006,131(3): 501-513.
    [50]Spicer L J, Aad P Y, Allen D, et al. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells[J]. Journal of Endocrinology,2006, 189(2):329-339.
    [51]Yoshino O, McMahon H E, Sharma S, et al. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse[J]. Proceedings of the National Academy of Sciences,2006,103(28):10678-10683.
    [52]Mulsant P, Lecerf F, Fabre S, et al. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(9):5104-5109.
    [53]Wilson T, Wu X Y, Juengel J L, et al. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells[J]. Biology of Reproduction,2001,64(4):1225-1235.
    [54]Pangas S A, Li X, Umans L, et al. Conditional Deletion of Smad1 and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice[J]. Mol Cell Biol,2008, 28(1):248-257.
    [55]Gueripel X, Brun V, Gougeon A. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion[J]. Biology of Reproduction, 2006,75(6):836-843.
    [56]Welt C, Sidis Y, Keutmann H, et al. Activins, Inhibins, and Follistatins:From Endocrinology to Signaling. A Paradigm for the New Millennium[J]. Experimental Biology and Medicine,2002, 227(9):724-752.
    [57]Bilezikjian L M, Blount A L, Donaldson C J, et al. Pituitary actions of ligands of the TGF-{beta} family:activins and inhibins[J]. Reproduction,2006,132(2):207-215.
    [58]Lee K B, Khivansara V, Santos M M, et al. Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone{beta} subunit transcription [J]. Journal of Molecular Endocrinology,2007,38(2):315-330.
    [59]Faure M O, Nicol L, Fabre S, et al. BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary[J]. Journal of Endocrinology,2005,186(1):109-121.
    [60]Nicol L, Faure M O, McNeilly J R, et al. Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in L{beta}T2 gonadotrophs[J]. Journal of Endocrinology,2008,196(3):497-507.
    [61]Huang H-J, Wu J C, Su P, et al. A Novel Role for Bone Morphogenetic Proteins in the Synthesis of Follicle-Stimulating Hormone[J]. Endocrinology,2001,142(6):2275-2283.
    [62]Otsuka F, Shimasaki S. A Novel Function of Bone Morphogenetic Protein-15 in the Pituitary: Selective Synthesis and Secretion of FSH by Gonado tropes [J]. Endocrinology,2002,143(12): 4938-4941.
    [63]Suszko M I, Woodruff T K. Cell-specificity of transforming growth factor-{beta} response is dictated by receptor bioavailability[J]. Journal of Molecular Endocrinology,2006,36(3):591-600.
    [64]Young J M, Juengel J L, Dodds K G, et al. The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures[J]. Journal of Endocrinology,2008,196(2):251.
    [65]Bondestam J, Kaivo-oja N, Kallio J, et al. Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells[J]. Molecular and Cellular Endocrinology,2002,195(1-2):79-88.
    [66]Miyazawa K, Shinozaki M, Hara T, et al. Two major Smad pathways in TGF-beta superfamily signalling[J]. Genes to Cells,2002,7(12):1191-1204.
    [67]Armstrong D G, Webb R. Ovarian follicular dominance:the role of intraovarian growth factors and novel proteins[J]. Reproduction,1997,2(3):139-146.
    [68]Ki K D, Tong S Y, Huh C Y, et al. Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers[J]. Gynecologic Oncology,2009,20(2):117-121.
    [69]Konrad L, Keilani M, Laible L, et al. Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro[J]. Apoptosis,2006,11(5):739-748.
    [70]Knight P G, Glister C. Local roles of TGF-[beta] superfamily members in the control of ovarian follicle development[J]. Animal Reproduction Science,2003,78(3-4):165-183.
    [71]Memon M A, Anway M D, Covert T R, et al. Transforming growth factor beta (TGF[beta]1, TGF[beta]2 and TGF[beta]3) null-mutant phenotypes in embryonic gonadal development[J]. Molecular and Cellular Endocrinology,2008,294(1-2):70-80.
    [72]Moustakas A, Heldin C H. Non-Smad TGF-beta signals[J]. J Cell Sci,2005,118(Pt 16):3573-3584.
    [73]Richards A J, Enders G C, Resnick J L. Activin and TGFbeta limit murine primordial germ cell proliferation[J]. Developmental Biology,1999,207(2):470-475.
    [74]Heyer J, Escalante-Alcalde D, Lia M, et al. Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis[J]. Proceedings of the National Academy of Sciences of the United States of America,1999,96(22):12595-12600.
    [75]Tremblay K D, Dunn N R, Robertson E J. Mouse embryos lacking Smadl signals display defects in extra-embryonic tissues and germ cell formation[J]. Development,2001,128(18):3609-3621.
    [76]Juengel J L, Bibby A H, Reader K L, et al. The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep[J]. Reproductive Biology and Endocrinology,2004, 78(2):1-11.
    [77]Schilling B, Yeh J. Expression of transforming growth factor (TGF)-[beta] 1, TGF-[beta]2, and TGF-[beta]3 and of type I and II TGF-[beta] receptors during the development of the human fetal ovary[J]. Fertility and Sterility,1999,72(1):147-153.
    [78]Chegini N, Williams R S. Immunocytochemical localization of transforming growth factors (TGFs) TGF-alpha and TGF-beta in human ovarian tissues [J]. The Journal of Clinical Endocrinology & Metabolism,1992,74(5):973-980.
    [79]Schmid P, Cox D, van der Putten H, et al. Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis:stored maternal TGF-beta 2 message in oocytes[J]. Biochemical and Biophysical Research Communications 1994,201(2):649-656.
    [80]Teerds K J, Dorrington J H. Immunohistochemical localization of transforming growth factor-beta 1 and -beta 2 during follicular development in the adult rat ovary[J]. Molecular and Cellular Endocrinology,1992,84(1-2):R7-13.
    [81]Nilsson E E, Doraiswamy V, Skinner M K. Transforming growth factor-beta isoform expression during bovine ovarian antral follicle development[J]. Molecular Reproduction & Development, 2003,66(3):237-246.
    [82]Bristol S K, Woodruff T K. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary[J]. Biology of Reproduction,2004,70(3):846-859.
    [83]May J V, Stephenson L A, Turzcynski C J, et al. Transforming growth factor beta expression in the porcine ovary:evidence that theca cells are the major secretory source during antral follicle development[J]. Biology of Reproduction,1996,54(2):485-496.
    [84]Gilchrist R B, Morrissey M P, Ritter L J, et al. Comparison of oocyte factors and transforming growth factor-beta in the regulation of DNA synthesis in bovine granulosa cells[J]. Molecular and Cellular Endocrinology,2003,201(1-2):87-95.
    [85]Liu X, Andoh K, Abe Y, et al. A Comparative Study on Transforming Growth Factor-{beta} and Activin A for Preantral Follicles from Adult, Immature, and Diethylstilbestrol-Primed Immature Mice[J]. Endocrinology,1999,140(6):2480-2485.
    [86]Yang P, Roy S K. Transforming Growth Factor B1 Stimulated DNA Synthesis in the Granulosa Cells of Preantral Follicles:Negative Interaction with Epidermal Growth Factor[J]. Biology of Reproduction,2006,75(1):140-148.
    [87]Ingman W V, Robker R L, Woittiez K, et al. Null Mutation in Transforming Growth Factor{beta} 1 Disrupts Ovarian Function and Causes Oocyte Incompetence and Early Embryo Arrest[J]. Endocrinology,2006,147(2):835-845.
    [88]Knight P G, Glister C. TGF-beta superfamily members and ovarian follicle development[J]. Reproduction,2006,132(2):191-206.
    [89]Magoffin D A, Gancedo B, Erickson G F. Transforming Growth Factor-{beta} Promotes Differentiation of Ovarian Thecal-Interstitial Cells but Inhibits Androgen Production [J]. Endocrinology,1989,125(4):1951-1958.
    [90]Dissen G A, Lara H E, Fahrenbach W H, et al. Immature rat ovaries become revascularized rapidly after autotransplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression[J]. Endocrinology,1994,134(3):1146-1154.
    [91]Osterlund C, Fried G. TGF{beta} receptor types I and II and the substrate proteins Smad 2 and 3 are present in human oocytes[J]. Molecular Human Reproduction,2000,6(6):498-503.
    [92]Mazerbourg S, Klein C, Roh J, et al. Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5[J]. Molecular Endocrinology,2004,18(3): 653-665.
    [93]Feary E S, Juengel J L, Smith P, et al. Patterns of Expression of Messenger RNAs Encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 During Follicular Development and Characterization of Ovarian Follicular Populations in Ewes Carrying the Woodlands FecX2W Mutation[J]. Biology of Reproduction,2007,77(6):990-998.
    [94]Wang Y, Fortin J, Lamba P, et al. Activator Protein-1 and Smad Proteins Synergistically Regulate Human Follicle-Stimulating Hormone{beta}-Promoter Activity[J]. Endocrinology,2008,149(11): 5577-5591.
    [95]Thackray V G, Mellon P L. Synergistic Induction of Follicle-Stimulating Hormone{beta}-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins[J]. Endocrinology, 2008,149(3):1091-1102.
    [96]Li Q, Pangas S A, Jorgez C J, et al. Redundant Roles of SMAD2 and SMAD3 in Ovarian Granulosa Cells In Vivo[J]. Molecular and Cellular Biology,2008,28(23):7001-7011.
    [1]李宁.动物遗传学(二版)[M].北京:中国农业出版社,2003.
    [2]赵有璋.羊生产学[M].北京:中国农业出版社.
    [3]赵洪波,鲁绍雄,连林生.绵羊多胎性的遗传机制及其育种改良研究进展[J],云南畜牧兽医,2006,(2):1-5.
    [4]李宁.基因组学技术在动物遗传育种中的应用[J].华南农业大学学报(自然科学版),26(S1):12-17.
    [5]Notter D R. Genetic aspects of reproduction in sheep[J]. Reprod Domest Anim,2008,43 (S2): 122-128.
    [6]Davis G H. Fecundity genes in sheep[J]. Animal Reproduction Science,2004,82-83(null):247-253.
    [7]Davis G H. Major genes affecting ovulation rate in sheep[J]. Genetics Selection Evolution,2005, 37(S1):S11-23.
    [8]Davis G H, Montgomery G W, Allison A J, et al. Segregation of a major gene influencing fecundity in progeny of Booroola sheep[J]. New Zealand Journal of Agricultural Research,1982,25(4): 525-529.
    [9]Bindon B M. Reproductive biology of the Booroola Merino sheep[J]. Australian journal of biological sciences,1984,37(3):163.
    [10]Montgomery G W, Lord E A, Penty J M, et al. The Booroola Fecundity (FecB) Gene Maps to Sheep Chromosome 6[J]. Genomics,1994,22(1):148-153.
    [11]Mulsant P, Lecerf F, Fabre S, et al. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(9):5104-5109.
    [12]Wilson T, Wu X Y, Juengel J L, et al. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells[J]. Biology of Reproduction,2001,64(4):1225-1235.
    [13]王根林,毛鑫智,George D,等.DNA分忻发现我国湖羊和小尾寒羊存在Booroola (FecB)多胎基因[J1.南京农业大学学报,2003,26(1):104-106.
    [14]管峰,刘守仁,程瑞禾,等.绵羊BMP-RIB基因多态性及其与中国美利奴肉用多胎品系产羔数和生长发育的相关性[J].南京农业大学学报,2005,28(2):75-79.
    [15]柴丽娟,赵先萍,刘文忠.绵羊主基因的研究进展[J].中国畜牧杂志,2003,39(3):51-52.
    [16]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP 15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [17]Bodin L, Di Pasquale E, Fabre S, et al. A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep[J]. Endocrinology,2007,148(1):393-400.
    [18]Hanrahan J P, Gregan S M, Mulsant P, et al. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries)[J]. Biology of Reproduction,2004,70(4):900-909.
    [19]Juengel J L, Hudson N L, Heath D A, et al. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J]. Biology of Reproduction, 2002,67(6):1777-1789.
    [20]Incerti B, Dong J, Borsani G, et al. Structure of the mouse growth/differentiation factor 9 gene[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research,1994,1222(1):125-128.
    [21]Bodensteiner K J, Clay C M, Moeller C L, et al. Molecular cloning of the ovine growth/differentiation factor-9 gene and expression of growth/differentiation factor-9 in ovine and bovine ovaries[J]. Biology of Reproduction,1999,60(2):381-386.
    [1]Xu R-H, Chen X, Li D S, et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast[J]. Nature Biotechnology,2002,20(12):1261-1264.
    [2]Montesano R, Sarki R, Schramek H. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells[J]. Biochemical and Biophysical Research Communications,2008,374(1):164-168.
    [3]Yang Y-L, Liu Y-S, Chuang L-Y, et al. Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-{beta} Receptors[J]. Endocrinology,2009,150(2):727-740.
    [4]Xiao Y-T, Xiang L-X, Shao J-Z. Bone morphogenetic protein[J]. Biochemical and Biophysical Research Communications,2007,362(3):550-553.
    [5]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [6]Lan H Y, Mu W, Tomita N, et al. Inhibition of Renal Fibrosis by Gene Transfer of Inducible Smad7 Using Ultrasound-Microbubble System in Rat UUO Model[J]. Journal of the American Society of Nephrology,2003,14(6):1535-1548.
    [7]Faure M O, Nicol L, Fabre S, et al. BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary[J]. Journal of Endocrinology,2005,186(1):109-121.
    [8]Lee K. B, Khivansara V, Santos M M, et al. Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone {beta} subunit transcription[J]. Journal of Molecular Endocrinology,2007,38(2):315-330.
    [9]Nicol L, Faure M O, McNeilly J R, et al. Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in L{beta}T2 gonadotrophs[J]. Journal of Endocrinology,2008,196(3):497-507.
    [10]Warburton D, Bellusci S. The molecular genetics of lung morphogenesis and injury repair[J]. Paediatric Respiratory Reviews,2004,5(Supplement 1):S283-S287.
    [11]Kim R Y, Robertson E J, Solloway M J. Bmp6 and Bmp7 Are Required for Cushion Formation and Septation in the Developing Mouse Heart[J]. Developmental Biology,2001,235(2):449-466.
    [12]Wang P Y, Koishi K, McLennan I S. BMP6 is axonally transported by motoneurons and supports their survival in vitro[J]. Molecular and Cellular Neuroscience,2007,34(4):653-661.
    [13]Huang H-J, Wu J C, Su P, et al. A Novel Role for Bone Morphogenetic Proteins in the Synthesis of Follicle-Stimulating Hormone[J]. Endocrinology,2001,142(6):2275-2283.
    [14]Eckery D C, Whale L J, Lawrence S B, et al. Expression of mRNA encoding growth differentiation factor 9 and bone morphogenetic protein 15 during follicular formation and growth in a marsupial, the brushtail possum (Trichosurus vulpecula)[J]. Molecular and Cellular Endocrinology,2002, 192(1-2):115-126.
    [15]Mulsant P, Lecerf F, Fabre S, et al. Mutation in bone morphogenetic protein receptor-ⅠB is associated with increased ovulation rate in Booroola Merino ewes[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(9):5104-5109.
    [16]Yang J, Davies R J, Southwood M, et al. Mutations in Bone Morphogenetic Protein Type Ⅱ Receptor Cause Dysregulation of Id Gene Expression in Pulmonary Artery Smooth Muscle Cells: Implications for Familial Pulmonary Arterial Hypertension[J]. Circulation Research,2008,102(10): 1212-1221.
    (17]张小辉,张路培,许尚忠,等.牛BMPR Ⅰ A基因cDNA的克隆及组织表达谱分忻[J].西北农林科技大学学报(自然科学版),2008,36(1):38-42.
    [18]Dick A, Risau W, Drexler H. Expression of Smad 1 and Smad 2 during embryogenesis suggests a role in organ development[J]. Developmental Dynamics,1998,211(4):293-305.
    [19]Gaussin V, Van de Putte T, Mishina Y, et al. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3[J]. Proceedings of the National Academy of Sciences,2002,99(5):2878-2883.
    [20]Kaivo-oja N, Jeffery L A, Ritvos O, et al. Smad signalling in the ovary[J]. Reproductive Biology and Endocrinology,2006,21(4):1-13.
    [21]Bondestam J, Kaivo-oja N, Kallio J, et al. Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells[J]. Molecular and Cellular Endocrinology,2002,195(1-2):79-88.
    [22]Pangas S A, Li X, Umans L, et al. Conditional Deletion of Smadl and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice[J]. Mol Cell Biol,2008, 28(1):248-257.
    [23]Gueripel X, Brun V, Gougeon A. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion[J]. Biology of Reproduction, 2006,75(6):836-843.
    [1]Welt C, Sidis Y, Keutmann H, et al. Activins, Inhibins, and Follistatins:From Endocrinology to Signaling. A Paradigm for the New Millennium[J]. Experimental Biology and Medicine,2002, 227(9):724-752.
    [2]Bilezikjian L M, Blount A L, Donaldson C J, et al. Pituitary actions of ligands of the TGF-{beta} family:activins and inhibins[J]. Reproduction,2006,132(2):207-215.
    [3]Lee K B, Khivansara V, Santos M M, et al. Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone {beta} subunit transcription[J]. Journal of Molecular Endocrinology,2007,38(2):315-330.
    [4]Faure M O, Nicol L, Fabre S, et al. BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary[J]. Journal of Endocrinology,2005,186(1):109-121.
    [5]Nicol L, Faure M O, McNeilly J R, et al. Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in L{beta}T2 gonadotrophs[J]. Journal of Endocrinology,2008,196(3):497-507.
    [6]Huang H-J, Wu J C, Su P, et al. A Novel Role for Bone Morphogenetic Proteins in the Synthesis of Follicle-Stimulating Honnone[J]. Endocrinology,2001,142(6):2275-2283.
    [7]Allendorph G P, Vale W W, Choe S. Structure of the ternary signaling complex of a TGF-β superfamily member[J]. Proceedings of the National Academy of Sciences,2006,103(20): 7643-7648.
    [8]Shi Y, Massagu J. Mechanisms of TGF-[beta] Signaling from Cell Membrane to the Nucleus[J]. Cell,2003,113(6):685-700.
    [9]Kaivo-oja N, Jeffery L A, Ritvos O, et al. Smad signalling in the ovary[J]. Reproductive Biology and Endocrinology,2006,21(4):1-13.
    [10]Guo X, Wang X-F. Signaling cross-talk between TGF-[beta]/BMP and other pathways[J]. Cell Research,2009,19(1):71-88.
    [11]Kirkbride K C, Townsend T A, Bruinsma M W, et al. Bone Morphogenetic Proteins Signal through the Transforming Growth Factor-{beta} Type Ⅲ Receptor[J]. The Journal of Biological Chemistry, 2008,283(12):7628-7637.
    [12]Otsuka F, Shimasaki S. A Novel Function of Bone Morphogenetic Protein-15 in the Pituitary: Selective Synthesis and Secretion of FSH by Gonadotropes[J]. Endocrinology,2002,143(12): 4938-4941.
    [13]Suszko M I, Woodruff T K. Cell-specificity of transforming growth factor-{beta} response is dictated by receptor bioavailability[J]. Journal of Molecular Endocrinology,2006,36(3):591-600.
    [14]Ho C C, Bernard D J. Bone Morphogenetic Protein 2 Signals via BMPR1A to Regulate Murine Follicle-Stimulating Hormone Beta Subunit Transcription [J]. Biology of Reproduction,2009,81(1): 133-141.
    [15]Young J M, Juengel J L, Dodds K G, et al. The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures[J]. Journal of Endocrinology,2008,196(2):251.
    [16]Moustakas A, Heldin C H. The regulation of TGFbeta signal transduction[J]. Development,2009, 136(22):3699-3714.
    [17]Wang Y, Fortin J, Lamba P, et al. Activator Protein-1 and Smad Proteins Synergistically Regulate Human Follicle-Stimulating Hormone {beta}-Promoter Activity[J]. Endocrinology,2008,149(11): 5577-5591.
    [18]Thackray V G, Mellon P L. Synergistic Induction of Follicle-Stimulating Hormone {beta}-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins[J]. Endocrinology, 2008,149(3):1091-1102.
    [19]Bondestam J, Kaivo-oja N, Kallio J, et al. Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells[J]. Molecular and Cellular Endocrinology,2002,195(1-2):79-88.
    [20]Miyazawa K, Shinozaki M, Hara T, et al. Two major Smad pathways in TGF-beta superfamily signalling[J]. Genes to Cells,2002,7(12):1191-1204.
    [1]王元兴闫玉琴,程瑞禾,等.湖羊繁殖力单项选育效果[J].当代畜牧,2000,0(4):31-32.
    [2]谢庄,程瑞禾,韩玉刚.湖羊公羊产羔效应的统计学分析[J].南京农业大学学报,1998,21(1):77-81.
    [3]Davis G H. Fecundity genes in sheep[J]. Animal Reproduction Science,2004,82-83(null):247-253.
    [4]管峰,艾君涛,刘守仁,等BMPR-IB和BMP15基因作为湖羊多胎性候选基因的研究[J].家畜生态学报,2005,26(3):9-12.
    [5]王根林,毛鑫智,George D,等.DNA分析发现我国湖羊和小尾寒羊存在Booroola (FecB)多胎基因[J].南京农业大学学报,2003,26(1):104-106.
    [6]储明星,成荣,陈国宏,等.小尾寒羊和湖羊高繁殖力候选基因BMP15的研究[J].安徽农业大学学报,2005,32(3):278-282.
    [7]储明星,桑林华,王金玉,等.小尾寒羊高繁殖力候选基因BMP15和GDF9的研究[J].遗传学报,2005,32(1):38-45.
    [8]储明星,孙洁,陈宏权,等.绵羊BMP15基因FecX-L突变的检测[J].中国农学通报,2007,23(10):85-88.
    [9]管峰,艾君涛,庞训胜,等.绵羊GDF-9和BMP15基因多态性检测[J].生命科学研究,2005,9(2):184-188.
    [10]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP 15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [11]Juengel J L, Reader K L, Bibby A H, et al. The role of bone morphogenetic proteins 2,4,6 and 7 during ovarian follicular development in sheep:contrast to rat[J]. Reproduction,2006,131(3): 501-513.
    [12]Yoshino O, McMahon H E, Sharma S, et al. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse[J]. Proceedings of the National Academy of Sciences,2006,103(28):10678-10683.
    [13]Souza C J, Campbell B K, McNeilly A S, et al. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry[J]. Reproduction,2002,123(3):363-369.
    [14]Osamu Hashimoto, R. Kelly Moore, Shimasaki S. Posttranslational processing of mouse and human BMP-15:Potential implication in the determination of ovulation quota[J]. Proceedings of the National Academy of Sciences of the United States of America,2005,102(15):5426-5431.
    [15]Pierre A, Pisselet C, Dupont J, et al. Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells[J]. Journal of Molecular Endocrinology, 2004,33(3):805-817.
    [16]Zhu G, Guo B, Pan D, et al. Expression of bone morphogenetic proteins and receptors in porcine cumulus-oocyte complexes during in vitro maturation[J]. Animal Reproduction Science,2008, 104(2-4):275-283.
    [17]Lee W S, Otsuka F, Moore R K, et al. Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat[J]. Biology of Reproduction,2001,65(4):994-999.
    [18]Tanwar P S, O'Shea T, McFarlane J R. In vivo evidence of role of bone morphogenetic protein-4 in the mouse ovary[J]. Animal Reproduction Science,2008,106(3-4):232-240.
    [19]Kaivo-oja N, Jeffery L A, Ritvos O, et al. Smad signalling in the ovary[J]. Reproductive Biology and Endocrinology,2006,21(4):1-13.
    [20]Edwards S J, Reader K L, Lun S, et al. The Cooperative Effect of Growth and Differentiation Factor-9 and Bone Morphogenetic Protein (BMP)-15 on Granulosa Cell Function Is Modulated Primarily through BMP Receptor Ⅱ[J]. Endocrinology,2008,149(3):1026-1030.
    [21]Fatehi A N, van den Hurk R, Colenbrander B, et al. Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development[J]. Theriogenology,2005,63(3):872-889.
    [22]Onagbesan O M, Bruggeman V, Van As P, et al. BMPs and BMPRs in chicken ovary and effects of BMP-4 and-7 on granulosa cell proliferation and progesterone production in vitro[J]. American Journal of Physiology-Endocrinology And Metabolism,2003,285(5):973-983.
    [23]Erickson G F, Shimasaki S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle[J]. Reproductive Biology and Endocrinology,2003,1(9):9-19.
    [24]Mulsant P, Lecerf F, Fabre S, et al. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes[J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(9):5104-5109.
    [25]Ruoss C, Tadros A, O'Shea T, et al. Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway[J]. Reproduction,2009,138(4):689-696.
    [26]Bondestam J, Kaivo-oja N, Kallio J, et al. Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells[J]. Molecular and Cellular Endocrinology,2002,195(1-2):79-88.
    [27]Moustakas A, Heldin C H. The regulation of TGFbeta signal transduction[J]. Development,2009, 136(22):3699-3714.
    [28]Pangas S A, Li X, Umans L, et al. Conditional Deletion of Smadl and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice[J]. Mol Cell Biol,2008, 28(1):248-257.
    [29]Gueripel X, Brun V, Gougeon A. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion[J]. Biology of Reproduction, 2006,75(6):836-843.
    [1]Knight P G, Glister C. TGF-beta superfamily members and ovarian follicle developmen[J]. Reproduction,2006,132(2):191-206.
    [2]Kaivo-oja N, Jeffery L A, Ritvos O, et al. Smad signalling in the ovary[J]. Reproductive Biology and Endocrinology,2006,21(4):1-13.
    [3]Juengel J L, Reader K L, Bibby A H, et al. The role of bone morphogenetic proteins 2,4,6 and 7 during ovarian follicular development in sheep:contrast to rat[J]. Reproduction,2006,131(3): 501-513.
    [4]Souza C J, Campbell B K, McNeilly A S, et al. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry[J]. Reproduction,2002,123(3):363-369.
    [5]Osamu Hashimoto, R. Kelly Moore, Shimasaki S. Posttranslational processing of mouse and human BMP-15:Potential implication in the determination of ovulation quota[J]. Proceedings of the National Academy of Sciences of the United States of America,2005,102(15):5426-5431.
    [6]McNatty K P, Galloway S M, Wilson T, et al. Physiological effects of major genes affecting ovulation rate in sheep[J]. Genetics Selection Evolution,2005,37 (S1):S25-38.
    [7]McNatty K P, Smith P, Moore L G, et al. Oocyte-expressed genes affecting ovulation rate[J]. Molecular and Cellular Endocrinology,2005,234(1-2):57-66.
    [8]Feary E S, Juengel J L, Smith P, et al. Patterns of Expression of Messenger RNAs Encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 During Follicular Development and Characterization of Ovarian Follicular Populations in Ewes Carrying the Woodlands FecX2W Mutation[J]. Biology of Reproduction,2007,77(6):990-998.
    [9]Abir R, Ben-Haroush A, Melamed N, et al. Expression of bone morphogenetic proteins 4 and 7 and their receptors IA, IB, and II in human ovaries from fetuses and adults[J]. Fertility and Sterility, 2008,89(5, Supplement 1):1430-1440.
    [10]Zhu G, Guo B, Pan D, et al. Expression of bone morphogenetic proteins and receptors in porcine cumulus-oocyte complexes during in vitro maturation[J]. Animal Reproduction Science,2008, 104(2-4):275-283.
    [11]Lee W S, Yoon S J, Yoon T K, et al. Effects of Bone Morphogenetic Protein-7 (BMP-7) on Primordial Follicular Growth in the Mouse Ovary[J]. Molecular Reproduction and Development, 2004,69(2):159-163.
    [12]Tanwar P S, O'Shea T, McFarlane J R. In vivo evidence of role of bone morphogenetic protein-4 in the mouse ovary[J]. Animal Reproduction Science,2008,106(3-4):232-240.
    [13]Shimasaki S, Zachow R J, Li D, et al. A functional bone morphogenetic protein system in the ovary[J]. Proceedings of the National Academy of Sciences of the United States of America,1999, 96(13):7282-7287.
    [14]Otsuka F, Moore R K, Shimasaki S. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary[J]. The Journal of Biological Chemistry,2001,276(35): 32889-32895.
    [15]Glister C, Kemp C F, Knight P G Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells:actions of BMP-4,-6 and-7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin[J]. Reproduction,2004,127(2):239-254.
    [16]Paradis F, Novak S, Murdoch G K, et al. Temporal regulation of BMP2, BMP6, BMP 15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig[J]. Reproduction,2009,138(1):115-129.
    [17]Fatehi A N, van den Hurk R, Colenbrander B, et al. Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development[J]. Theriogenology,2005,63(3):872-889.
    [18]Edwards S J, Reader K L, Lun S, et al. The Cooperative Effect of Growth and Differentiation Factor-9 and Bone Morphogenetic Protein (BMP)-15 on Granulosa Cell Function Is Modulated Primarily through BMP Receptor II[J]. Endocrinology,2008,149(3):1026-1030.
    [19]Ruoss C, Tadros A, O'Shea T, et al. Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway[J]. Reproduction,2009,138(4):689-696.
    [20]管峰,艾君涛,刘守仁,等.BMPR-IB和BMP15基因作为湖羊多胎性候选基因的研究[J].家 畜生态学报,2005,26(3):9-12.
    [21]Erickson G F, Shimasaki S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle[J]. Reproductive Biology and Endocrinology,2003,1(9):9-19.
    [22]Onagbesan O M, Bruggeman V, Van As P, et al. BMPs and BMPRs in chicken ovary and effects of BMP-4 and-7 on granulosa cell proliferation and progesterone production in vitro[J]. American Journal of Physiology-Endocrinology And Metabolism,2003,285(5):973-983.
    [23]Bondestam J, Kaivo-oja N, Kallio J, et al. Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells[J]. Molecular and Cellular Endocrinology,2002,195(1-2):79-88.
    [24]Moustakas A, Heldin C H. The regulation of TGFbeta signal transduction[J]. Development,2009, 136(22):3699-3714.
    [25]Tremblay K D, Dunn N R, Robertson E J. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation [J]. Development,2001,128(18):3609-3621.
    [26]Chang H, Huylebroeck D, Verschueren K, et al. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects[J]. Development,1999,126(8):1631-1642.
    [27]Pangas S A, Li X, Umans L, et al. Conditional Deletion of Smad1 and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice[J]. Mol Cell Biol,2008, 28(1):248-257.
    [28]Gueripel X, Brun V, Gougeon A. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion[J]. Biology of Reproduction, 2006,75(6):836-843.
    [1]Shi Y, Massagu J. Mechanisms of TGF-[beta] Signaling from Cell Membrane to the Nucleus[J]. Cell,2003,113(6):685-700.
    [2]Massague J, Seoane J, Wotton D. Smad transcription factors[J]. Genes & development,2005, 19(23):2783-2810.
    [3]Lan H Y, Mu W, Tomita N, et al. Inhibition of Renal Fibrosis by Gene Transfer of Inducible Smad7 Using Ultrasound-Microbubble System in Rat UUO Model[J]. Journal of the American Society of Nephrology,2003,14(6):1535-1548.
    [4]Zhang S, Fei T, Zhang L, et al. Smad7 Antagonizes Transforming Growth Factor {beta} Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation[J]. Molecular and Cellular Biology,2007,27(12):4488-4499.
    [5]Ki K D, Tong S Y, Huh C Y, et al. Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers[J]. Gynecologic Oncology,2009,20(2):117-121.
    [6]Konrad L, Keilani M, Laible L, et al. Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro[J]. Apoptosis,2006,11(5):739-748.
    [7]Drummond A E. TGFβ signalling in the development of ovarian function[J]. Cell and Tissue Research,2005,322(1):107-115.
    [8]Knight P G, Glister C. Local roles of TGF-[beta] superfamily members in the control of ovarian follicle development[J]. Animal Reproduction Science,2003,78(3-4):165-183.
    [9]Memon M A, Anway M D, Covert T R, et al. Transforming growth factor beta (TGF[beta]1, TGF[beta]2 and TGF[beta]3) null-mutant phenotypes in embryonic gonadal development[J]. Molecular and Cellular Endocrinology,2008,294(1-2):70-80.
    [10]Prevot, Bouret, Croix, et al. Evidence That Members of the TGFβ Superfamily Play a Role in Regulation of the GnRH Neuroendocrine Axis:Expression of a Type I Serine-Threonine Kinase Receptor for TGRP and Activin in GnRH Neurones and Hypothalamic Areas of the Female Rat[J]. Journal of Neuroendocrinology,2000,12(7):665-670.
    [11]Fevre-Montange M, Dumontel C, Chevallier P, et al. Localization of Transforming Growth Factors, TGFβ1 and TGF β 3, in Hypothalamic Magnocellular Neurones and the Neurohypophysis[J]. Journal of Neuroendocrinology,2004,16(7):571-576.
    [12]Sarkar D K, Boyadjieva N I. Ethanol alters production and secretion of estrogen-regulated growth factors that control prolactin-secreting tumors in the pituitary [J]. Alcoholism:Clinical and Experimental Research,2007,31(12):2101-2105.
    [13]Sarkar D K, Chaturvedi K, Oomizu S, et al. Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-{beta} 1, and TGF-{beta} Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes[J]. Endocrinology,2005,146(10):4179-4188.
    [14]Juengel J L, Bibby A H, Reader K L, et al. The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep[J]. Reproductive Biology and Endocrinology,2004, 78(2):1-11.
    [15]Liu X, Andoh K, Abe Y, et al. A Comparative Study on Transforming Growth Factor-{beta} and Activin A for Preantral Follicles from Adult, Immature, and Diethylstilbestrol-Primed Immature Mice[J]. Endocrinology,1999,140(6):2480-2485.
    [16]Ingman W V, Robker R L, Woittiez K, et al. Null Mutation in Transforming Growth Factor{beta}l Disrupts Ovarian Function and Causes Oocyte Incompetence and Early Embryo Arrest[J]. Endocrinology,2006,147(2):835-845.
    [17]Knight P G, Glister C. TGF-beta superfamily members and ovarian follicle development [J]. Reproduction,2006,132(2):191-206.
    [18]Magoffin D A, Gancedo B, Erickson G F. Transforming Growth Factor-{beta} Promotes Differentiation of Ovarian Thecal-Interstitial Cells but Inhibits Androgen Production[J]. Endocrinology,1989,125(4):1951-1958.
    [19]Jones R L, Stoikos C, Findlay J K, et al. TGF-{beta} superfamily expression and actions in the endometrium and placenta[J]. Reproduction,2006,132(2):217-232.
    [20]Gaide Chevronnay H P, Cornet P B, Delvaux D, et al. Opposite Regulation of Transforming Growth Factors-{beta}2 and -{beta}3 Expression in the Human Endometrium[J]. Endocrinology,2008, 149(3):1015-1025.
    [21]Rodriguez G C, Rimel B J, Watkin W, et al. Progestin Treatment Induces Apoptosis and Modulates Transforming Growth Factor-β in the Uterine Endometrium [J]. Cancer Epidemiology Biomarkers & Prevention,2008,17(3):578-584.
    [22]孙莹张,王成方,胡诗婉,兰珍TGF-β-1及其受体在不孕患者粘连、闭锁输卵管伞部的表达及意义[J].四川大学学报(医学版),2009,40(3):435-438.
    [23]Pohlers D, Brenmoehl J, Loffler I, et al. TGF-beta and fibrosis in different organs - molecular pathway imprints[J]. Biochim Biophys Acta,2009,1792(8):746-756.
    [24]Gu L, Zhu Y-j, Yang X, et al. Effect of TGF-[beta]/Smad signaling pathway on lung myofibroblast differentiation[J]. Acta Pharmacologica Sinica,2007,28(3):382-391.
    [25]Ask K, Bonniaud P, Maass K, et al. Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3[J]. International Journal of Biochemistry and Cell Biology,2008,40(3):484-495.
    [26]Pittet J-F, Griffiths M J D, Geiser T, et al. TGF-β is a critical mediator of acute lung injury[J]. The Journal of Clinical Investigation,2001,107(12):1537-1544.
    [27]Heinemeier K M, Olesen J L, Haddad F, et al. Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types[J]. The Journal of Physiology,2007,582(3):1303-1316.
    [28]Zhou L, Porter J D, Cheng G, et al. Temporal and spatial mRNA expression patterns of TGF-[beta]1, 2,3 and T[beta]RⅠ,Ⅱ,Ⅲ in skeletal muscles of mdx mice[J]. Neuromuscular Disorders,2006, 16(1):32-38.
    [29]Osterlund C, Fried G. TGF{beta} receptor types Ⅰ and Ⅱ and the substrate proteins Smad 2 and 3 are present in human oocytes[J]. Molecular Human Reproduction,2000,6(6):498-503.
    [30]Schmid P, Cox D, van der Putten H, et al. Expression of TGF-beta s and TGF-beta type Ⅱ receptor mRNAs in mouse folliculogenesis:stored maternal TGF-beta 2 message in oocytes[J]. Biochemical and Biophysical Research Communications 1994,201(2):649-656.
    [31]Bristol S K, Woodruff T K. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary[J]. Biology of Reproduction,2004,70(3):846-859.
    [32]Mazerbourg S, Klein C, Roh J, et al. Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5[J]. Molecular Endocrinology,2004,18(3): 653-665.
    [33]Juengel J L, Hudson N L, Heath D A, et al. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J]. Biology of Reproduction, 2002,67(6):1777-1789.
    [34]Feary E S, Juengel J L, Smith P, et al. Patterns of Expression of Messenger RNAs Encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 During Follicular Development and Characterization of Ovarian Follicular Populations in Ewes Carrying the Woodlands FecX2W Mutation[J]. Biology of Reproduction,2007,77(6):990-998.
    [35]Lin H-Y, Qian D, Zhang X, et al. Gene expression of transforming growth factor-[beta] receptors types I and II in rat endometrium during the estrous cycle and early pregnancy[J]. Life Sciences, 2006,78(23):2669-2675.
    [36]Kubota K, Omori Y, Ikeda S, et al. Expression and Cyclic Change of Betaglycan in the Rat Oviduct[J]. The Journal of Reproduction and Development,2009,55(2):200-205.
    [37]Lin H-Y, Wang H-M, Li Q-L, et al. Expression of Smad2 and Smad4, transforming growth factor-[beta] signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation[J]. Animal Reproduction Science,2004,80(3-4):303-316.
    [38]Li Q, Pangas S A, Jorgez C J, et al. Redundant Roles of SMAD2 and SMAD3 in Ovarian Granulosa Cells In Vivo[J]. Molecular and Cellular Biology,2008,28(23):7001-7011.
    [39]Fuchshofer R, Stephan D A, Russell P, et al. Gene expression profiling of TGF[beta]2-and/or BMP7-treated trabecular meshwork cells:Identification of Smad7 as a critical inhibitor of TGF-[beta]2 signaling[J]. Experimental Eye Research,2009,88(6):1020-1032.
    [40]Dooley S, Hamzavi J, Ciuclan L, et al. Hepatocyte-Specific Smad7 Expression Attenuates TGF-[beta]-Mediated Fibrogenesis and Protects Against Liver Damage[J]. Gastroenterology,2008, 135(2):642-659.
    [1]Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP 15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nature Genetics,2000,25(3):279-283.
    [2]Juengel J L, Reader K L, Bibby A H, et al. The role of bone morphogenetic proteins 2,4,6 and 7 during ovarian follicular development in sheep:contrast to rat[J]. Reproduction,2006,131(3): 501-513.
    [3]Yoshino O, McMahon H E, Sharma S, et al. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse[J]. Proceedings of the National Academy of Sciences,2006,103(28):10678-10683.
    [4]Shi Y, Massagu J. Mechanisms of TGF-[beta] Signaling from Cell Membrane to the Nucleus[J]. Cell,2003,113(6):685-700.
    [5]Juengel J L, Bibby A H, Reader K L, et al. The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep[J]. Reproductive Biology and Endocrinology,2004, 78(2):1-11.
    [6]Saragueta P E, Lanuza G M, Baranao J L. Autocrine role of transforming growth factor beta1 on rat granulosa cell proliferation [J]. Biology of Reproduction,2002,66(6):1862-1868.
    [7]Magoffin D A, Gancedo B, Erickson G F. Transforming Growth Factor-{beta} Promotes Differentiation of Ovarian Thecal-Interstitial Cells but Inhibits Androgen Production[J]. Endocrinology,1989,125(4):1951-1958.
    [8]Gilchrist R B, Morrissey M P, Ritter L J, et al. Comparison of oocyte factors and transforming growth factor-beta in the regulation of DNA synthesis in bovine granulosa cells[J]. Molecular and Cellular Endocrinology,2003,201(1-2):87-95.
    [9]Kubota T, Kamada S, Taguchi M, et al. Autocrine/paracrine function of transforming growth factor-beta 1 in porcine granulosa cells[J]. Hum Reprod,1994,9(11):2118-2122.
    [10]Knecht M, Feng P, Catt K. Bifunctional role of transforming growth factor-beta during granulosa cell development[J]. Endocrinology,1987,120(4):1243-1249.
    [11]Liu X, Andoh K, Abe Y, et al. A Comparative Study on Transforming Growth Factor-{beta} and Activin A for Preantral Follicles from Adult, Immature, and Diethylstilbestrol-Primed Immature Mice[J]. Endocrinology,1999,140(6):2480-2485.
    [12]Yang P, Roy S K. Transforming Growth Factor B1 Stimulated DNA Synthesis in the Granulosa Cells of Preantral Follicles:Negative Interaction with Epidermal Growth Factor[J]. Biology of Reproduction,2006,75(1):140-148.
    [13]Ingman W V, Robker R L, Woittiez K, et al. Null Mutation in Transforming Growth Factor{beta} 1 Disrupts Ovarian Function and Causes Oocyte Incompetence and Early Embryo Arrest[J]. Endocrinology,2006,147(2):835-845.
    [14]Knight P G, Glister C. TGF-beta superfamily members and ovarian follicle development [J]. Reproduction,2006,132(2):191-206.
    [15]Osterlund C, Fried G TGF{beta} receptor types Ⅰ and Ⅱ and the substrate proteins Smad 2 and 3 are present in human oocytes[J]. Molecular Human Reproduction,2000,6(6):498-503.
    [16]Schilling B, Yeh J. Expression of transforming growth factor (TGF)-[beta] 1, TGF-[beta]2, and TGF-[beta]3 and of type Ⅰ and Ⅱ TGF-[beta] receptors during the development of the human fetal ovary[J]. Fertility and Sterility,1999,72(1):147-153.
    [17]Mazerbourg S, Klein C, Roh J, et al. Growth Differentiation Factor-9 Signaling Is Mediated by the Type Ⅰ Receptor, Activin Receptor-Like Kinase 5[J]. Molecular Endocrinology,2004,18(3): 653-665.
    [18]Juengel J L, Hudson N L, Heath D A, et al. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J]. Biology of Reproduction, 2002,67(6):1777-1789.
    [19]Feary E S, Juengel J L, Smith P, et al. Patterns of Expression of Messenger RNAs Encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 During Follicular Development and Characterization of Ovarian Follicular Populations in Ewes Carrying the Woodlands FecX2W Mutation[J]. Biology of Reproduction,2007,77(6):990-998.
    [20]Schmid P, Cox D, van der Putten H, et al. Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis:stored maternal TGF-beta 2 message in oocytes[J]. Biochemical and Biophysical Research Communications 1994,201(2):649-656.
    [21]Bristol S K, Woodruff T K. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary[J]. Biology of Reproduction,2004,70(3):846-859.
    [22]Li Q, Pangas S A, Jorgez C J, et al. Redundant Roles of SMAD2 and SMAD3 in Ovarian Granulosa Cells In Vivo[J]. Molecular and Cellular Biology,2008,28(23):7001-7011.
    [23]Lan H Y, Mu W, Tomita N, et al. Inhibition of Renal Fibrosis by Gene Transfer of Inducible Smad7 Using Ultrasound-Microbubble System in Rat UUO Model[J]. Journal of the American Society of Nephrology,2003,14(6):1535-1548.
    [24]Zhang S, Fei T, Zhang L, et al. Smad7 Antagonizes Transforming Growth Factor{beta} Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation[J]. Molecular and Cellular Biology,2007,27(12):4488-4499.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700