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一. 哺乳动物排卵和黄体萎缩机理的研究
全面揭示了由组织型纤溶酶激活因子tPA 和和它的抑制因子(PAI-1)所介导的细胞外基质(ECM)局部降解在排卵和黄体萎缩中的生理功能,作出了系统性和创造性贡献,提出了排卵机制的新假说;同时揭示了tPA/PAI-1系统所介导的ECM局部降解在调控黄体萎缩过程中也起重要作用，提出了新观点，开拓了新研究领域。上述研究对推动生殖生物学和畜牧临床医学学科发展发挥了重要作用。该项研究共发表SCI/EI论文60余篇,有SCI他引引文639次,在国际上产生了较大影响，为中国在本领域研究争得一席之地。为蛋白质组学研究分子间的“激活”与“抑制”机制提供了一个重要例证
1. 20多年研究,系统揭示了由纤溶酶原激活因子（PA）和其抑制因子(PAI-1)所介导的细胞外基质（ECM）局部降解在排卵和黄体萎缩中的生理功能,作出了自主性,原创性和系统性贡献。发表论文77篇(其中SCI/SCI-E收录论文60余篇。他们的研究发现,卵巢卵细胞和颗粒细胞(GC)表达tPA,膜间质细胞(TC)表达其抑制因子PAI-1，两者在卵泡不同细胞中的协同表达导致局部定向蛋白水解产生,诱发排卵；发现除已知排卵激素LH/hCG外,其他激素GnRH,FSH和VIP也能通过诱导卵子和GC tPA表达诱发排卵；发现能抑制GCtPA表达的消炎疼能抑制排卵;刺激TC PAI－1表达的促乳素能抑制排卵;证实灵长类排卵同样是由卵泡GC tPA和TC PAI－1协同表达调控的；发现GC产生的抑制素(Inhibin)通过抑制卵细胞tPAmRNA翻译控制卵细胞tPA活性。在上述一系列研究基础上，提出了排卵机制的新假说。
2. 排卵后GC和TC转化为黄体,黄体分泌孕酮维持妊娠。首次发现黄体（CL）继续表达tPA和PAI－1，两者在CL发育后期协同表达诱发黄体萎缩，提出了黄体萎缩的新观点,开拓了新研究领域。
3．对tPA和PAI-1在卵巢不同细胞中的协同表达和相互作用的发现,为蛋白质组学在生理水平上研究分子间的"激活"与"抑制"机制提供了一个典型例证。
本研究对探索经济动物多排卵调控方法和发展女性避孕新途径提供了新的研究思路和理论基础。
35 篇在排卵和黄体萎缩研究领域中代表性论文目录
1. YI-XUN LIU*, KUI LIU, QIANG FENG, ZHAO-YUAN HU, HAI-ZHEN LIU, GUO-QING FU, YIN-CHUAN LI, RU-JIN ZOU, and Tor NY (2004):Tissue-type Plasminogen Activator and Its Inhibitor Plasminogen Activator Inhibitor Type 1 Are Coordinately Expressed during Ovulation in the Rhesus Monkey. Endocrinology 145: 1767-1775
2.KUI LIU, QIANG FENG, HONG-JUAN GAO, ZHAO-YUAN HU,RU-JIN ZOU,YIN-CHUAN LI, AND YI-XUN LIU*,(2003): Expression and Regulation of Plasminogen Activators, Plasminogen Activator Inhibitor type-1 and steroidogenic acute regulatory protein in the Rhesus Monkey Corpus Luteum. Endocrinology, 2003, 144 (8): 3611-3617
3. Liu YX*, Ny T, Sarkar D, Loskutoff D and Hsueh AJW (1986): Identification and regulation of tissue plasminogen activator activity in rat cumulus-oocyte complexes. Endocrinology 119 : 1578- 1587
4.Yi-Jun Chen, Qiang Feng and Yi-Xun Liu* (1999): Expression of the Steroidogenic Acute Regulatory Protein and Luteinizing Hormone Receptor and Their Regulation by Tumor Necrosis Factor α in Rat Corpora Lutea. Biol Reprod. 60: 419-427.
5. Yi-xun Liu+*, Xiao-rong Peng, Hai-zhen Liu, Yi-jun Chen and Ny T (1998): Prolactin Regulation of Tissue Type Plasminogen Activator and Plasminogen Activator Inhibitor Type-1 Gene Expression in eCG-Primed Rat Granulosa cells in culture. Biol Reprod 59:409-416
6. Liu Yi-xun*, Peng Xiao-rong, Carrico Whitney and Ny Tor (1998): Prolactin delays gonadotropin-induced ovulation and down-regulates expression of the plasminogen activator system in the ovary. Human Reproduction 12: 2748-2755
7. Liu Kui, Liu Yi-xun*, Hu Zhao-yuan, Chen Yi-jun, Mu Xiao-min and Ny Tor (1997): Temporal expression of urokinase type plasminogen activator plasminogen activator inhibitor type-1 and LH receptor mRNA in the corpus luteum of rhesus monkey during gonadotropin-induced luteolysis. Mol. Cell. Endocrinol.133: 109-11
8. Liu K, Brandstom A, Liu YX, Ny T* (1996): Coordinated expression of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 during corpus luteum formation and luteolysin in the adult pseudopregnant rat.Endocrinology 137:2126-2133
9. Liu Yi-Xun*, Chen Ya-Xiong, Shi Fa-Wu and Feng Qiang (1995): Studies on the Role of Plasminogen Activators and Plasminogen Activator Inhibitor Type-1 in Rat Corpus Luteum of Pregnancy. Biol. Reprod. 53 : 1131-1138
10. Feng Q, Liu K, Zou RJ and Liu YX* (1993): The possible involvement of tissue type plasminogen activator in luteolysis of rhesus monkey. Human Reproduction 8:1640-1644
11. Liu YX (1999): Regulation of plasminogen activator system in the ovary Biological Signals and Receptors 8: 160-177
12. Liu YX, Cajander SB, Ny T, Krestensen P and Hsueh AJW (1987): Gonadotropin regulation of tissue and urokinase types of plasminogen activator in rat granulosa and theca- interstitial cells during periovulatory periods. Mol.Cell.Endocrinol.54:221–229
13. Liu YX and Hsueh AJW (1987): Plasminogen activator activity in cumulus-oocyte complexes of gonadotropin-treated rats during periovulatory periods. Biol.Reprod. 36:1055-1062
14. Liu YX, Kasson BG, Dahl KD and Hsueh AJW (1987): Vasoactive interstitial peptide stimulates plasminogen activator activity by cultured rat granulosa cells and cumulus-oocyte complexes. Peptides 8(1): 29-33
16. Liu YX and Hsueh AJW (1986) : Synergism between granulosa and theca-interstitial cells in estrogen biosynthesis by gonadotropin-treated rat ovaries : Studies on the two-cel1, two-gonadotropin hypothesis using steroid antisera。Biol.Reprod.35:27-36
17. Liu YX, Peng XR and Ny T (1991) : Tissue-specific and time-coordinated hormone regulation of plasminogen-activator-inhibitor type 1 and tissue-type plasminogen activator in the rat ovaryduring gonadotropin-induced ovulation Eur.J.Biochem.195:549-555
18. Yi-xun-Liu(2004): PLASMINOGEN ACTIVATOR/PLASMINOGEN ACTIVATOR INHIBITORS IN OVARIAN PHYSIOLOGY. Frontiers in Bioscience 9, 3356-3373
19. Fu-Qing Yu, Chun-Sheng Han, Wei Yang, Xuan Jin, Zhao-Yuan Hu, and Yi-Xun Liu* (2005) Activation of p38 MAPK pathway by FSH regulates steroidogenesis in granulosa cells differentially J. Endocrinol 186(1):85-96
20. Xuan Jin, Chun-Sheng Han, Xue-Sen Zhang, Fu-Qing Yu, Shu-Hua Guo, Zhao-Yuan Hu and Yi-Xun Liu* (2005): Stem cell factor modulates the expression of steroidogenesis related proteins and FSHR during ovarian follicular development Frontiers in Biosciences 10: 1573-1580
21. Chen YJ ,Feng Q and Liu YX* (1999): Expression of steroidogenic acute regulatory protein (StAR) and its regulation by TNF-a in rat corpus lutea Recent Progress in Molecular.Comparative Endocrinology P63-70 eds by H.B. Kwon, JMP Joss and SI Shii, Kwanggju, Republic of Korea 1999
22. Liu YX*, Feng Q and Liu K (1999): Comparative studies on the role of plasminogen activators and plasminogen activator inhibitor type 1 in luteal regression in rhesus monkey,rat and mouse .Recent Progress in Molecular Comparative Endocrinology P57-62 , 1999, eds by HB Kwon, JMP Joss and SI Shii 8
23. Fu-Qing Yu, Chun-Sheng Han, Wei Yang, Xuan Jin, Zhao-Yuan Hu, and Yi-Xun Liu* (2005) ROLE OF ERK1/2 IN FSH-INDUCED PCNA EXPRESSION AND STEROIDOGENESIS IN GRANULOSA CELLS Frontiers in Biosciences 10:896-904
24. Jin X, Yu FQ, Wei P, Hu ZY, Han CS, Liu YX* (2005): Signal transduction of stem cell factor in promoting early follicle development Mol Cell Endocrinil 229 (1-2): 3-10
25. Jin X, Yu FQ, Wei P, Hu ZY, Han CS, Liu YX* (2005): Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction. Mol Reprod Dev. 2005 28;70(1):82-90
26.Hongjuan Gao, Xin-Lei Chen, Zhi-Hong Zhang, Xin-Xin Song, Zhao-Yuan Hu and Yi-Xun Liu* (2005) IFN-gamma and TNF-Alpha inhibit expression of TGF-beta-1, its receptors TbetaR-I and TbetaR-II in the corpus luteum of PMSG/hCG treated rhesus monkey Frontiers in Biosciences 10:2496-2503
27. Hsueh AJW, Liu YX, Cajander S, Peng XR, Dahl K, Kristensen P and Ny T (1988): Gonadotropin-releasing hormone induces ovulation in hypophysectomized rats : Studies on ovarian tissue-type plasminogen activator activity, messenger ribonucleic acid content and cellular localization. Endocrinology 122 : 1486-1495
28. Kessel Bruce, Liu YX, Jia XC and Hsueh AJW (1985) : Autocrine role of estrogen in augmentation of luteinizing hormone receptor formation in cultured rat granulosa cel1s. Biol. Reprod. 32 : 1038-1050
29. Ny T, Liu YX, Ohlsson M, Peng XR, Jia XC and Hsueh AJW (1990): Hormone regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type 1 gene expression in ovary. In Major Advances in Female Reproduction. eds by Adashi E Y and Mancusos. 77-84
30. Ny T, Liu YX, Ohlsson M, Peng XR, Jia XC and Hsueh AJW (1990): Hormone regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type 1 gene expression in ovary. In Major Advances in Female Reproduction. eds by Adashi E Y and Mancusos.
31. Siler-Khdor TM, Yu FQ, Wei P, Tao SX and Liu YX (2004): Contraceptive action of a GnRH II analog in the rhesus monkey ?J Clin Endocrinol and Metab? 2004, 89(9): 4513-4520
32. Cuiling Lu, Wei Yang, Min Chen, Tao Liu, Junling Yang, Ping Tan, Zhaoyuan Hu, and Yixun Liu*(2009): InhibinA Inhibits Follicle Stimulating Hormone (FSH) Action by Suppressing its Receptor Expression in Cultured Rat Granulosa Cells ?Mol Cell Endocrinology 298(2009):48-56
33. Wei Yang, Zhao-Yuan Hu and Yi-Xun Liu (2008): Mitogenactivated protein kinase regulates FSH-induced expression of tissue-type plasminogen activator through an AP-1 response element Endocrine 2008 Dec;34(1-3):101-7. Epub 2008 Nov 4.
34. LiuYi-Xun（2007）：Interaction and signal transduction between oocyte and samatic cells in the ovary. Front Biosci. 2007 May 1; 12:2782-96.
35. Siler-Khodr TM, Yu FQ, Wei P, Tao SX, Coulhart S, Mactyszczyk S, Liu YX（2006）.Dose-related actions of GnRH II analog in the cycling rhesus monkey. Contraception. 21 74(2): 157-64
二. 精子发生特异基因的克隆和分子机理的研究
1. 我们建立了“隐睾”和“43℃局部温浴睾丸”两种“热压”非人灵长类动物模型。热压和长效睾酮皆能诱发生精细胞凋亡，并且是一个可逆的过程。初步实验证实，长效睾酮和“热压”是通过不同的信息通路引发精细胞凋亡，前者主要引发Ⅶ－Ⅷ期生精细胞凋亡，而后者主要影响Ⅰ－Ⅳ期和Ⅸ－ⅩⅢ期精细胞凋亡，两者合并使用有叠加效用。
2. 通过对大鼠和非人灵长类隐睾模型的研究和用Affymetrix寡核苷酸芯克隆到7个对温度敏感的精子发生相关基因,其中 T6-441, Trs4, Afaf, Rshl2 和TSNHE 5个基因有潜在的应用前景(Trs4和Afaf两个基因在精细胞顶体上表达; Rshl2和TSNHE二个基因在精子尾部表达)。Trs4 (GenBank Accession number DQ132434)全长3100bp，推测其编码一个789aa的蛋白。Afaf 定位于精细胞膜上,在顶体发生和精子成熟期均有表达，表达量随顶体的形成和延长而增加，在附睾精子顶体上仍有微量表达。我们推测Afaf在精子发生过程中，特别是在顶体形成过程中具有重要作用。通过酵母双杂交法和体外结合试验,我们钓取出与Trs4相互作用的六个结合蛋白，其中Rshl2 （radial spoke head-like 2）即放射辅头样蛋白2，此蛋白是一细胞骨架蛋白，可能参与维持精子结构的完整性和精子运动, Rshl2蛋白定位于精子尾部,可能与精子运动相关。我们从隐睾模型芯片中发现一个明显变化的寡聚核苷酸来源的基因unigen，TSNHE是unigen表达的蛋白,RT-PCR检测，该基因在睾丸特异表达,其 mRNA在精母细胞表达；其蛋白在延长型精子尾部表达；蛋白包括566个氨基酸，具有多个跨膜区；经western检测，该基因只有一种形式蛋白特异在睾丸表达。通过蛋白比对发现， TSNHE定位於具有钠氢通道蛋白区和钠钾通道蛋白区。己知钠氢通道蛋白缺失的个体,因严重失去精子运动能力导致完全不育。我们推测TSNHE可能调节精子的活力和受精能力。 因为:TRS4, Afaf, 定位在成熟精子顶体上,而Rshl2和TSNHE都定位在延长型精子尾部,因此有潜在的应用前景。有望发展阻断精子顶体反应和精子运动发展男性避孕药的可能性。
3. 建立了离体生精细胞,Sertoli细胞培养实验模型,检测热激或与TU组合对各细胞中基因表过达的影响,研究热激诱发Sertoli细胞去分化的分子机理和信号转导途径。系统研究了温度和睾酮诱导生精细胞凋亡的分子机制,研究了各种标记分子和诱发凋亡的相关分子的表达和信息通路, 研究了:1)生精细胞增值标志分子ki67; 2)热休克蛋白和热休克蛋白转录因子Hsp105,Hsp60, Hsp70, HSF1; 3)Fas,FasL,Bax/BcL2,P53等细胞凋亡诱发分子; 4).E2F1与孤儿受体.LHR-1; 5) 支持细胞的去分化标志分子与信号通路相关标志分子。重点研究了隐睾和43℃水浴处理成年恒河猴和大鼠Sertoli细胞后, Sertoli细胞可逆性地去分化的分子调控机制; 研究了LHR-1和DAX-1基因在调控Sertoli细胞去分化过程的作用; 研究了热激对Sertoli细胞抑制素,FSH受体,雄激素受体以及芳香化酶活性的影响。研究了睾酮对Sertoli细胞骨架降介分子tPA/PAI-1系统和相关粘附分子的影响,及其tPA/PAI-1在生精过程中的重要作用，该项研究成果已发表SCI论文50余篇。
36 篇在精子发生与基因克隆研究领域中代表性论文目录
1. Liu Yi-Xun （2007）:Involvement of plasminogen activator and plasminogen activator inhibitor type 1 in spermatogenesis, sperm capacitation, and fertilization. Semin Thromb Hemost. 2007 Feb; 33 (1):29-40. PMID: 17253187 [PubMed - in process]
2. Li YC, Hu XQ, Zhang KY, Guo J, Hu ZY, Tao SX, Xiao LJ, Wang QZ, Han CS, Liu YX*(2006).Afaf, a novel vesicle membrane protein, is related to acrosome formation in murine testis. FEBS Lett. 2006 Jun 16; [Epub ahead of print] PMID: 16831425 [PubMed - as supplied by publisher]
3.Guo J, Tao SX, Chen M, Shi YQ, Zhang ZQ, Li YC, Zhang XS, Hu ZY, Liu YX* （2007）Heat treatment induces liver receptor homolog-1 expression in monkey and rat Sertoli cells. Endocrinology. (2007):48:1255-1265
4.X-S Zhang,Z-H Zhang, X Jin1, P Wei, X-Q Hu M Chen, C-L Lu, Y-He Lue, S-H Guo ,J-X Yuan, Z-Y Hu, C-S Han, A P. S Hikim, R S. Swerdloff, C Wang and Yi-Xun Liu*（2006）: Dedifferentiation of Adult monkey Sertoli cells Through Activation of ERK1/2 Kinase Induced by Heat treatment Endocrinology. 2006 147(3):1237-1245
5. Xue-Sen Zhang, Zhi-Hong Zhang, Shu-Hua Guo, Wei Yang, Zhu-Qiang Zhang, Jin-Xiang Yuan, Xuan Jin, Zhao-Yuan Hu, and Yi-Xun Liu*（2006）；Activation of extracellular signal-regulated kinase 1 and 2 in Sertoli cells of the experimental cryptorchidism of adult rhesus monkey Asia J Andrology 2006 May;8(3):265-72.
6. X-S Zhang, J-X Yuan, Y-H Lue, S-X Tao, S-H Guo, X Jin, T Liu, Z-Y Hu, A P. S Hikim, RS. Swerdloff , C Wang and Yi-Xun Liu*.（2006） Expression of orphan receptors TR2, TR3, TR4, and p53 in heat-treated testis of cynomolgus monkeys (Macaca fascicularis).J Androl. 27(3 ):405-13.
7. Y LUE, C.WANG, Y-X LIU, A P. S HIKIM, X-S ZHANG, C NG, Z-Y HU, Y-C LI，A LEUNG and RS. SWERDLOFF(2006)：Transient Testicular Warming Enhances the Suppressive Effect of Testosterone on Spermatogenesis in Adult Cynomolgus Monkeys (Macaca fascicularis) J．Clin Endocrinol Metabol,2006 91(2): 539-545
8. Tao SX, Guo J, Zhang XS, Li YC, Hu ZY, Han CS and Liu YX* (2006):Germ cell apoptosis induced by experimental cryptorchdism is mediated by multiple molecular pathways in cynomolgus macaque Frontier in Bioscience 2006, Jan 11: 1077-89
9.Xin-xin Song, Yin-chuan Li, Yu-qiang Shi, Xiao-qian Hu, Zhao-yuan Hu, Chun-sheng Han and Yi-Xun Liu* (2006):CLONING AND CHARACTERIZATION OF A NOVEL SPERMIOGENESIS-RELATED GENE,T6441, IN RAT TESTIS Frontiers in Bioscience 1:143-150
10. Xue-Sen Zhang1, Yah-He Lue2, Shu-Hua Guo1, Jin-Xiang Yuan1, Zhao-Yuan Hu1, Chun-Sheng Han1, Amiya P. Sinha Hikim2, Ronald S. Swerdloff 2, Christina Wang2 and Yi-Xun Liu*(2005)* :EXPRESSION OF HSP105 AND HSP60 DURING GERM CELL APOPTOSIS IN THE HEAT-TREATED TESTES OF ADULT CYNOMOLGUS MONKEYS (MACACA FASCICULARIS) Frontiers in Bioscience 10:3110-3121
11. Zhang ZH, Song XX, Xiao LJ, Han CS, Zou RJ and Liu YX* (2004): Expression of intermediate filaments in the testis of rhesus monkey during heat-stress induced azoospermia or oligozoospermia International J. Andrology 27(4): 234-239
12. Liu Yi-Xun (2004): CONTROL OF SPERMATOGENESIS IN PRIMATE AND PROSPECT OF MALE CONTRACEPTION Arcieves of Andrology (Review paper), 51: 77-92
13. Zhang ZH, Zhou XC, Wei P, Hu ZY and Liu YX* (2003): Expression of BcL-2 and Bax in rhesus monkey testis during germ cell apoptosis induced by testoterone undecanoate Archives of Andrology 49: 439-447
14. Zhang Z.-H,Hu Z-Y, Zou R-J, Jin X, Zhang X-S, Han C-S, Liu Y-X *(2003): BCL-2 and BAX is involved in testicular germ cell apoptosis induced by by experimental cryptorchildism in rhesus monkey Contraception 68:297-301
15. Liu YX*, Xiao SB (2003): Development of population and reproductive medicine in China 266-283 in Science Progress in China, Eded by Lu Yongxiang, Science press 2003
16. Han XB, Zhou XC, Hu ZY, Zhang ZH and Liu YX* (2002): Cloning and characterization of temperature-related gene TRS1 Archives of Andrology 48: 273-280
17. Zhou Xin-Chang,Wei Peng, Hu Zhao-Yuan, Gao Fei, Zhou Ru-Jin, LiuYi-Xun *(2001): Role of apoptosis related genes Fas/FasL in azoospermia or oligozoospermia induced by testosterone undecanoate in rhesus monkey Acta Phamacol. Sinica 11: 1028-1033
18. Zhou XC, Wei P, Hu ZY< Han XB, Zhou RJ and Liu YX *(2002): Expression of P16 in testis of rhesus monkey during heat stress and testosterone undecanoate induced azoospermia or oligozoospermia Contraception 65: 251-255
19. Zhou XC, Zhang ZH, Hu ZY, Zhou RJ and Liu YX* (2002): Expression of Hsp 70-2 in rhesus monkey by testosterone undecanoate Contraception 66: 377-382
20. Zhou XC, Han XB, Hu ZY, Zhou RJ and Liu YX* (2001): Expression of Hsp 70-2 in unilateral cryptorchid testis of rhesus monkey during germ cell apoptosis Endocrine 16: 89-95
21. Guo CX, Jie Ma, Zhou XC, Liu YX* (2001): Expression of hSP 70-2 gene during germ cell apoptosis in rat unilateral cryptorchid testes.Archives. of Andrology. 46(2):109-115
22. Zhou Xin-Chang,Wei Peng, Hu Zhao-Yuan, Gao Fei, Zhou Ru-Jin, Liu Yi-Xun * (2001): Role of apoptosis related genes Fas/FasL in azoospermia or oligozoospermia induced by testosterone undecanoate in rhesus monkey Acta Phamacol. Sinica 11: 1028-1033
23. Guo CX, Jie Ma, Zhou XC, Liu YX (2001): Expression of hSP 70-2 gene during germ cell apoptosis in rat unilateral cryptorchid testes. Archives. of Andrology. 46(2):109-115
24. Liu K, Liu YX*, Du Q, Zhou an, Lin X, Hu ZY, Zhang GY and Zhang GH (1996) : Preliminary studies on the role of plasminogen activator in seminal plasma of human and rhesus monkey. Mol. Human Reprod. 2: 99-104
25. Liu YX, Du Q, Liu K and Fu GQ (1995): Hormonal regulation of plasminogen activator in rat and mouse seminiferous epithelium. Biological Signals 4 : 232-240
26. Liu YX*, Liu K, Zhou HM, Du Q, Hu ZY and Zou RJ (1995) :Hormonal regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured monkey Sertoli cell. Human Reproduction 10 (3) :719-727
27. Mu XM, Liu YX, Cllins LL and Chang C (2000): The P53/Rb-mediated repression of testicular orptan receptor-2 in the Rhesus monkey with cryptorchichidism J. Biol. Chem (31): 23877-23883
28. Mu XM, Young WJ, Liu YX, Uemura H and Chang CS (1998): Induction of an intronic enhancer of the human ciliary neurotropic factor receptor (NTRFa) Gene by the TR3 orphan receptor. Endocrine 9 (1): 27-32.
29. Zhang Tong Guo CX, Hu ZY and Liu Yi-xun* (1997): Localization of plasminogen activator and inhibitor, LH receptor, androgen receptor and inhibin subunits in monkey epididymis. Mol. Human Reproduction 11:945-952.
30. Zhang T, Zhou HM and Liu YX*(1997): Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin subunits in rhesus monkey testes. Mol Human Reprod. 3:223-231
31.Min Chen, Jun-Ling Yang, Cui-Ling Lu, Tao Liu, Wei Yang, Jian Guo, Shi-Xin Tao, Xiao-Qian Hu, Cui-Hong Fan, Zhao-Yuan Hu, Fei Gao and Yi-Xun Liu (2008): Effect of heat stress on expression of junction-associated molecules and upstream factor AR and WT1 in monkey Sertoli cells? ?Endocrinology 2008 Oct;149(10):4871-82. Epub 2008 Jun 5.Jun 5. [Epub ahead of print, PMID: 18535113
32. Min Chen, Jin-Xiang Yuan, Yu-Qiang Shi, Xue-Sen Zhang, Zhao-Yuan Hu, Fei Gao, Yi-Xun Liu (2008):. Effect of 43 degrees treatment on expression of heat shock proteins 105, 70 and 60 in cultured monkey Sertoli cells. Asian J. Andrology 2008 May;10(3):474-85.
33.Hu XQ, Ji SY, Li YC, Fan CH, Cai H, Yang JL, Zhang CP, Chen M, Pan ZF, Hu ZY, Gao F, Liu YX (2009) Acrosome formation-associated factor is involved in fertilization.Fertil Steril. 2009 Mar 12. [Epub ahead of print] PMID: 19285662 [PubMed - as supplied by publisher]
34.Jian Guo1,2,3, Yue Jia 1,4, Shi-Xin Tao2, Yin-Chuan Li2, Xue-Sen Zhang2, Zhao-Yuan Hu2 , Naomi Chiang 4, Yan-He Lue4, Amiya P. Sinha Hikim4, Ronald S. Swerdloff 4, Christina Wang4 and Yi-Xun Liu2 * (2009): Expression of nitric oxide synthase during germ cell apoptosis in testis of cynomolgus monkey after testosterone and heat treatment ?J Androl. 2009 Mar-Apr;30(2):190-9. Epub 2008 Oct 2.
35. Jian Guo, Shi-Xin Tao, Wei Yang, Yin-Chuan Li, Zhao-Yuan Hu and Yi-Xun Liu (2007):Testosterone regulation of tissue type plasminogen activator and plasminogen activator inhibitor type-1 expression in monkey and rat testes Endocrine 2007 Aug;32(1):83-9.
36. LiuYX（2007）：Involvement of plasminogen activator and plasminogen activator inhibitor type 1 in spermatogenesis, sperm capacitation, and fertilization. SeminThromb Hemost. 2007 Feb; 33(1): 29-40.
三. 胚胎植入分子机理的研究
远从1993年来我们就开始相关的研究。在1999年通过国际性27个申请实验室三轮评审和自由竞争，WHO/洛氏基金专家评审委员会从中选出六个实验室建立了由美国，英国，德国，中国 （我们研究组），澳大利亚和印度所组成的六个国际合作研究中心。我们建立了非人灵长类动物模型，研究证实,在灵长类植入“窗口”期的子宫内膜发生细胞凋亡,血管新生和与组织重建相关的细胞外基质降解;这三个过程是协调/同步发生，在时间和空间上彼此相关，相互依赖。能抑制上述过程的化合物能有效地阻止胚胎植入。
在CONRAD/CICCR基金会支持下,我们硏究了Ⅱ型GnRH抗胚胎植入的分子机。研究表明,在排卵后1－6天,给予缓释Ⅱ型GnRH，可100％阻止妊娠，而对血中促性腺激素，卵巢甾体激素没有影响，未发现有明显副作用。Ⅱ型GnRH抗胚胎植入的作用可能发生在不同细胞水平上，如影响受精，抑制受精卵运行和子宫内膜的特异性变化，阻止胚胎着床和胎盘形成等。上述发现己发表在 J.Clin.in Endocrinol Metab。
25篇在胚胎植入研究领域中代表性论文目录
1. Xiao LJ, Yuan JX, Song XX, Li YC, Hu ZY, Liu YX* (2006). Expression and regulation of stanniocalcin 1 and 2 in rat uterus during embryo implantation and decidualization.
Reproduction. 2006 131(6):1137-49. PMID: 16735553 [PubMed -in process]
2. Siler-KhodrTM*, Yu FQ, Wei P, Tao SX, Coulhart S, Mactyszczyk S,Liu Y(2006):.Dose-related actions of GnRH II analog in the cycling rhesus monkey. Contraception. 2006 Aug;74(2):157-64. Epub 2006 Apr 27. PMID: 16860054 [PubMed - in process
3. L-J Xiao, J-X Yuan, Y-C Li, R Wang，, Z-Y Hu and Y-X Liu* (2005): Extracellular Ca2+ Sensing Receptor Expression and Hormonal Regulation in Rat Uterus during the Peri-implantation Period Reproduction129:779-788
4. LI-JUAN XIAO XIN-XIN SONG, YIN-CHUAN LI, JIN-XIANG YUAN, ZHAO-YUAN HU and YI-XUN LIU* (2005) : Expression and regulation of stanniocalcin 1 and 2 in rat uterus during embryo implantation and decidualization Reproduction 2006 Jun;131(6):1137-49.
5. Liu Yi-Xun (2004): Endometrium implantation and ectopic pregnancy (Review) Sciences in China C 47(4): 293-302
6. Wei P, Chen XL, Song XX, Hu ZY and Liu YX *(2004): VEGF, bFGF and their receptors in the endometrium of rhesus monkey during menstrual and early pregnancy Mol Reproduction Develoment 68 (4): 456-462
7. Siler-Khdor TM*, Yu FQ, Wei P, Tao SX and Liu YX* (2004): Contraceptive action of a GnRH II analog in the rhesus monkey J Clin Endocrinol and Metab 2004, 89(9): 4513-4520
8. Wei p, Jin X, Xiao LJ, Liu YX* (2004): Expression of Fas,FasL, bcL-2 and Bax in the endometrium of rhesus monkey during the menstrual cycle and pregnancy Mol Reprod and Develop 70(4): 478-484
9. Wei P, Jin X, Zhang XS, Han CS and LiuYX* (2005): Expression of bcl-2 and P53 at the fetal-maternal interface of rhesus monkey Reprod Biol Endocrinol. 2005 Jan 14;3(1):4 [Epub ahead of print] PMID: 15649334 [PubMed - as supplied by publisher]
10. Liu Yi-Xun (2005): Involvement of molecules related to angiogenesis, proteolysis and apoptosis in implantation in rhesus monkey and mouse Contraception (Review paper)Apr;71(4):249-62
11.Wei P, Chen XL, Song XX, Hu ZY and Liu YX* (2004): VEGF, bFGF and their receptors in the endometrium of rhesus monkey during menstrual cycle and early pregnancy Placenta 25: 184-196
12. Wei P, Jin X, Tao CS and Liu YX* (2004): Apoptosis and P53 expression in the implantation site of rhesus monkey in the normal and drug-induced abortion Acta Physiol Sinica 56(1):60-65
13. Liu Y X (2004): Endometrium implantation and ectopic pregnancy Science in China B 34(2): 105-112
14. Liu YX (2004): Progress in male contraceptive research in China Progress in Nature Science 14:249-255
15. Wei P, Zhang ZH, Chen XL and Liu YX (2003): Expression and function of AA98, a newly found vascular endothelial cell related factor at the maternal-embyyonic boundary of rhesus monkey Chinese Sci. Bulletin 48(9):881-886
16.Wei P, Yuan JX, Jin X Hu ZY and LiuYX*(2003): Molsidomine and N omega-nitro-L-arginine methyl ester affect apoptosis in mouse endometrium Acta Pharmcol Sinica 24: 24(12):1177-1184
17.Gao Fei, Xu Fu-Hua, Zhou Xin-Chang, Han Xiao-Bin and Liu Yi-Xun* (2001): Mifepristoneregulates expression of apoptosis related genes Fas and FasL in mouse endometrium. Acta Pharmacol. Sinica 22 (6): 524-529
18. Fei Gao,Xin-Lei Chen,Peng Wei, Hong-Juan Gao, Yi-Xun Liu *(2001): Expression of matrix metalloproteinase-2, tissue inhibitors of metaloproteinase-1,-3 at the implantation site of rhesus monkey during the early stage of pregnancy. Endocrine 15(2): 5-12
19. Feng Q, Liu K, Liu YX, Byrne S and Ocklefed CD (2001): Plasminogen activators and inhibitors are transcribed during early mataque implantation Placenta 22:186-199
20. Feng Q, Liu YX, Liu K, Byrne S, Liu GZ, Wang XL, Li ZX and Ockleford CD.(2000): Expression of urokinase plasminogen activitor, inhibitor and urokinase receptor in pregnant rhesus monkey uterus during early placentation. Placenta. 21(2):184-193.
21. Hu ZY, Liu YX, Zou RJ and Ockleford C (1999): Expression of tissue type and urokinase type plasminogen activators as well as their inhibitors type 1 and type 2 in the placentea of human
and rhesus monkey. J. Anatomy ( London ) 194:183-195
22. King, RJB and Liu YX (1979): Studies on the effect of oestrodiol-induced protein on DNA synthesis by cultured cells. Research on Steroid 8 : 19-26
23. Liu YX(1979) :Studies on purification of estrogen-induced protein from rat uterus and its physiological role in cultured cells. Sciencia Sinica 22(2):222-236
24. Nie G, Li Y, Wang M, Liu YX, Findlay JK, Salamonsen LA (2004): Uterine PC6 Blocks Embryo Implantation: An Obligatory Role for a Proprotein Convertase in Fertility. Biol Reprod. 2005 Apr;72(4):1029-36.
25. Luu KC, Nie GY, Hampton A, Fu GQ, Liu YX, Salmonsen LA (2004): Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation. Reproduction 128(4): 433-441
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