哺乳动物的妊娠起始于囊胚的滋养层细胞与子宫内膜识别、黏附，并进一步向子宫内膜侵袭，将胚胎锚定在子宫壁上。伴随胚胎发育，胚胎滋养层细胞活跃增殖和分化，对子宫内膜基质和螺旋动脉进行改建和重构，建立完善的子宫-胎盘-胎儿循环，保障胎儿宫内发育。因而，胎盘发育是哺乳动物妊娠成功建立和维持的重要保障。胎盘发育不完善将引起一系列复杂的妊娠相关疾病，如子痫前期、复发流产、胎儿生长受限等，对母儿近远期健康都造成严重危害。

    迄今，对人类胎盘的认识依然是个“黑匣子”，其发育调控机理及其介导的母体妊娠适应性调节机制仍有待阐明，而与之密切相关的妊娠重大疾病的预测、防治和干预也亟待突破。

    本研究组在前沿科学问题和国家重大需求引导下，致力于研究胎盘发育和妊娠维持的调控机制，以及妊娠高血压、复发流产等重大妊娠疾病的发病机理。旨在揭开人类妊娠健康的神秘面纱，并为发展重要妊娠疾病的预测和干预策略奠定坚实的科学基础。

    建立和稳定了包括人滋养层干细胞系、早期及足月人胎盘原代滋养层细胞、滋养层细胞-血管内皮细胞三维共培养、蜕膜dNK细胞等体外研究模型，并稳定了CYP19-Cre、ELF5-Cre介导或慢病毒/腺病毒介导的胎盘特异基因操作小鼠模型。发现了mTOR信号介导的滋养层细胞合体化通过巨胞饮方式适应环境营养压力的机制，阐释了蛋白质糖基化修饰调节滋养层细胞分化的路径，揭示了子宫螺旋动脉改建进程中血管内滋养层细胞的免疫调节功能及平滑肌细胞的去分化命运，系统阐释了母胎界面上妊娠适应性的细胞和分子调控网络。通过与多中心临床单位协作，建立了多种妊娠疾病前瞻性资源库，鉴定了子痫前期等妊娠疾病的早期预测标志物；解析了母胎界面多细胞互作及母体妊娠适应性的分子通路紊乱参与子痫前期、FGR、复发性流产等疾病发生发展的机理。在Cell Stem Cell, PNAS, Hypertension等期刊发表研究论文近百篇。

    我们的主要研究兴趣是胎盘发育和妊娠维持的调控机制，并以此为切入点研究子痫前期和复发流产等重大妊娠疾病的病因学。具体的研究内容包括：1. 胎盘滋养层细胞发育分化的谱系编程机制；2. 子宫-胎盘-胎儿循环的构建机制；3. 母胎界面多细胞互作建立免疫适应性的分子基础；4. 子痫前期、复发流产等重要妊娠疾病的病因学。

    研究目标是：综合利用临床样本库、体外模型和小鼠模型，将胎盘发育及功能研究与临床重大疾病机制和干预策略探索相结合，揭开人类胎盘发育和妊娠维持调控的分子机理，为发展重要妊娠疾病的预测和干预策略奠定坚实的科学基础。

每年度招收博士研究生和硕士研究生各一名

100104-病理学与病理生理学

胎盘发育及妊娠相关疾病
生殖免疫调节

1993-09--1998-07   中国科学院动物研究所   理学博士
1988-09--1993-07   中国科学技术大学   理学学士

   

2004-10~现在, 中国科学院动物研究所, 研究员
2001-05~2004-09,中国科学院动物研究所, 副研究员
1999-05~1999-09,香港大学, 访问学者
1998-07~2001-04,中国科学院动物研究所, 助理研究员

2017-01-01-今,“Biology of Reproduction”杂志编委, 编委
2017-01-01-今,中国免疫学会生殖免疫分会, 副主任委员
2017-01-01-今,中华预防医学会生命早期发育与疾病防控专业委员会, 副主任委员
2016-01-01-今,妇幼健康研究会母胎医学专业委员会, 副主任委员
2015-01-01-今,中国生理学会生殖生理专业委员会, 理事
2014-01-01-今,《中华围产医学杂志》编委, 编委
2013-12-31-今,中国动物学会生殖生物学专业委员会, 副秘书长
2013-07-30-今,Placenta期刊编委, 中国区编委
2012-06-01-今,CoLab for Pregnancy国际组织执行委员会委员,
2012-01-02-今,PLoS ONE 期刊编委会, Academic Eidtor

现代生殖医学之病理概论
辅助生殖技术
生殖疾病概论
生殖生物学
生殖生物学seminar

   

（1） 中国科学院朱李月华优秀教师奖, 研究所（学校）, 2021
（2） 全国妇幼健康科学技术奖, 二等奖, 国家级, 2017
（3） 子宫内膜异位症的基础与临床研究, 二等奖, 国家级, 2007
（4） 全国人口和计划生育科技工作先进个人, , 部委级, 2006
（5） 子宫内膜异位症的基础与临床研究, 一等奖, 省级, 2005

（ 1 ） 纤溶酶抑制因子的抑制剂用于预防或治疗子痫前期或子痫的用途, 发明专利, 2019, 第 1 作者, 专利号: 201910987566.0

（ 2 ） 用于预测或早期诊断妊娠高血压疾病的试剂盒, 发明专利, 2014, 第 1 作者, 专利号: PCT/CN2014/074071

（ 3 ） 一株人类胚胎滋养层细胞系的建立及其应用, 发明专利, 2008, 第 1 作者, 专利号: ZL200510086506.X

   

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HGF/ c-Met signal regulates early differentiation of placental trophoblast cells. J Reprod Dev. 2021, [12] 王雁玲. Zhen XX#, Yang L#, Gu Y, Yang Q, Gu WW, He YP, Wang YL*, Wang J*. MNSFbeta Regulates TNFalpha Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFbeta in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss. Front Immunol. 2021, [13] 王雁玲. Bian X, Liu J, Yang Q, Liu Y, Jia W, Zhang X, Li YX, Shao X*, Wang YL*. miR-210 regulates placental adaptation to maternal hypoxic stress during pregnancy.. Biol Reprod. 2021, [14] 王雁玲. Shao X#, Cao G#, Chen D#, Liu J, Yu B, Liu M, Li YX, Cao B*, Sadovsky Y*, Wang YL*. Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply.. PNAS. 2021, [15] 王雁玲. Ma Y#, Yu X#, Zhang L#, Liu J, Shao X, Li YX, Wang YL*. Uterine decidual niche modulates the progressive dedifferentiation of spiral artery vascular smooth muscle cells during human pregnancy.. Biol Reprod.. 2021, [16] 王雁玲. Ma Y#, Yang Q#, Fan M#, Zhang L, Gu Y, Jia W, Li Z, Wang F, Li YX, Wang J, Li R*, Shao X*, Wang YL*. Placental endovascular extravillous trophoblasts (enEVTs) educate maternal T-cell differentiation along the maternal-placental circulation.. Cell Proliferation.. 2020, [17] 王雁玲. Li Z#, Bian X#, Ma Y, Yang Q, Jia W, Liu J, Wang F, Liu M, Li YX, Shao X*, Wang YL*.Uterine Scarring Leads to Adverse Pregnant Consequences by Impairing the Endometrium Response to Steroids.. Endocrinology. 2020, [18] 王雁玲. Wang H#, Zhao Y#, Luo R, Bian X, Wang Y, Shao X, Li YX, Liu M*, Wang YL*. A positive feedback self-regulatory loop between miR-210 and HIF-1αmediated by CPEB2 is involved in trophoblast syncytialization: implication of trophoblast malfunction in preeclampsia.. Biol Reprod.. 2020, [19] 王雁玲. Xu P#, Li Z#, Wang Y#, Yu X, Shao X, Li YX, Peng C, Zhao Y*, Wang YL*. miR-18a Contributes to Preeclampsia by Downregulating Smad2 (Full Length) and Reducing TGF-β Signaling.. Mol Ther Nucleic Acids.. 2020, [20] 王雁玲. Xu P#, Li Z#, Wang Y#, Yu X, Shao X, Li YX, Peng C, Zhao Y*, Wang YL*. MiR-18a contributes to pre 1 eclampsia by downregulating Smad2 (full-length) and reducing transforming growth factor-β signaling.. Molecular Therapy - Nucleic Acids.. 2020, [21] 王雁玲. Xuan Shao, Yongqing Wang, Yanlei Liu, Xuejiang Guo, Dong Li, Ran Huo, Wentong Jia, Guangming Cao, Yu-Xia Li, Ming Liu, Jiahao Sha, Yangyu Zhao, and Yan-Ling Wang. Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia.. Journal of Hypertension. 2019, [22] 王雁玲. Lin L, Li G, Zhang W, Wang Y* and Yang H*. Low-dose aspirin reduces hypoxia-induced sFlt1 release via the JNK/AP-1 pathway in human trophoblast and endothelial cells.. Journal of Cellular Physiology. 2019, [23] 王雁玲. Hao Wang, Yangyu Zhao, Rongcan Luo, Xiaotao Bian, Yongqing Wang, Xuan Shao, Yu-xia Li, Ming Liu, Yan-Ling Wang. A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytiolization: implication of trophoblast malfunction in preeclampsia Self-regulatory loop for trophoblast malfunction.. Biology of Reproduction. 2019, [24] 王雁玲. Shao X#, Tan C, Chen D, Wang YL*. Placental defects are involved in most gene mutations that cause embryonic and fetal death. Biol Reprod. 2018 Sep 1;99(3):476-478. Biol Reprod. 2018, [25] 王雁玲. Li G#, Ma L, Lin L, Wang YL, Yang H*. The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the NF-κB pathway. Biol Reprod. 2018 Aug 1;99(2):422-432.. Biol Reprod. 2018, [26] 王雁玲. Dai J#, Liang K, Zhao S, Jia W, Liu Y, Wu H, Lv J, Cao C, Chen T, Zhuang S, Hou X, Zhou S, Zhang X, Chen XW, Huang Y, Xiao RP, Wang YL, Luo T, Xiao J, Wang C*. Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis. Proc Natl Acad Sci U S A. 2018 Jun 11. pii: 201801745.. Proc Natl Acad Sci U S A. 2018, [27] 王雁玲. Wang H#, Zhang L, Guo X, Bai Y, Li YX, Sha J, Peng C, Wang YL*, Liu M. MiR-195 modulates oxidative stress-induced apoptosis and mitochondrial energy production in human trophoblasts via flavin adenine dinucleotide-dependent oxidoreductase domain-containing protein 1 and pyruvate dehydrogenase phosphatase regulatory subunit. 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（1） 子宫生物学转化研究,  Effect of matrix metalloproteinase-26 on cell invasion and its modulation by gonadotropin releasing hormones in human trophoblast cells. In Translational research in Uterine Biology, Elsevier, 2008-07, 第 1 作者
（2） 子宫内膜疾病的新进展, Progress of Endometrial Disease, 清华同方电子光盘出版社, 2010-10, 第 5 作者
（3） 黄荷凤, 陈子江, 刘嘉茵, 王雁玲, 孙斐, 李蓉. 生殖医学 [M], Reproductive Medicine, 人民卫生出版社, 2021-03, 第 4 作者

   

（ 1 ） 母胎互作调控紊乱致复发流产和子痫前期等妊娠疾病的分子机制, 负责人, 国家任务, 2015-01--2019-12
（ 2 ） 胎盘类固醇激素调节机体凝血-纤溶平衡和妊娠结局的机制, 负责人, 国家任务, 2016-01--2019-12
（ 3 ） 中国人群辅助生殖人口与子代队列建立与应用基础研究, 参与, 国家任务, 2016-07--2021-06
（ 4 ） 妊娠过程中类固醇激素合成和代谢紊乱导致子痫前期发生发展的机制, 负责人, 国家任务, 2018-01--2022-12
（ 5 ） 胎盘形成的分子机制, 负责人, 国家任务, 2018-12--2021-12
（ 6 ） 谱系发育异常与胚胎停育及早期流产, 参与, 国家任务, 2021-12--2024-11

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曾辛  博士研究生  071003-生理学  

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