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Yan-Ling WANG, Ph. D.

Regulation of placenta development, pregnancy adaptation, and the pathogenesis of pregnancy disorders (preeclampsia and recurrent spontaneous abortion) derived from placental defects.


Staffs: Yu-xia Li, Ming Liu
Post-Doctors: Xuan Shao
PhD Candidates: Liyang Ma, Hao Wang, Guanlin Li, Guangming Cao, Yanlei Liu, Huifen Lu,Wentong Jia, Yamei Jiang, Xiaotao Bian, Yeling Ma

• WANG Group website

 

Generally, we are investigating the regulation of placenta development,pregnancy adaptation, and the pathogenesis of pregnancy disorder (preeclampsia) derived from placental defects.

The formation of the placenta is one of the critical events in mammalian pregnancy. Owing to the appropriately controlled invasion of uterine stroma and spiral arteries by placental trophoblasts, the utero-placental circulation can be successfully formed. Failures in the regulatory network of trophoblast functions will lead to serious clinical complications, such as preeclampsia (PE), recurrent spontaneous abortion (RSA), intrauterine growth retardation (IUGR), etc. The disorders affects around 30% of human pregnancies and brings severe burden for maternal and perinatal care, even causes health problems for the affected mothers and children in their long-term development. By far, the regulatory mechanisms of human placenta development as well as the pathogenesis of preeclampsia remain poorly understood.

During the past several years, we set up some in vitro research models including the primary culture and immortalized cell lines of human early-pregnancy trophoblasts at various differentiation status, placental explant cultures, 3 dimensional co-culture of human decidual NK (dNK) cells, trophoblastic cells and endothelial cells, mouse trophoblast stem cells, etc. We also maintained CYP19-Cre-mediated orlentivirus-mediated placenta-specific gene manipulated mouse models in this lab. Through cooperating with several clinical centers, a prospective Chinese Han pregnancy cohort was established, and several candidate plasma biomarkers for PE were successfully identified. Further investigation on the working mechanisms whereby the biomarkers function in placental development and pregnancy adaptation are carried out. Meanwhile, the study on the fine interaction among dNK cells, trophoblast cells and endothelial cells at the maternal-fetal interface are ongoing, in order to clarify how deficient dNK cell function participate in the occurrence of RSA. Currently we are addressing:

  1. The physiological coordination between the placenta and multiple maternal organs in response to pregnancy, also known as pregnancy adaptation.
  2. Based on the identification of specific biomarkers for preeclampsia, the roles of HGF/c-Met signaling, mTOR signaling and various microRNAs in the human placentation.
  3. The interactions between dNK cells and many other cell types at the feto-maternal interface, in order to figure out how deficient dNK cell function participate in the occurrence of preeclampsia.
  4. Development of reliable and specific molecular targets for early diagnosis and intervention of severe PE and RSA.
Our long-term goal is to reveal genetic and/or epigenetic basis of preeclampsia, and figure out reliable strategies for early diagnosis and intervention of severe preeclampsia. At the same time, by comparing normal and abnormal pregnancies, we hope to get better understanding on the critical checkpoint in placenta development that governs pregnancy outcomes.



High specific circulating biomarkers for severe preeclampsia - sMet
Accurately prediction for severe preeclampsia at gestational week 15-26
PCT/CN2014/07407; Patent No. 201310436215.3



Multiple microRNAs was epigenetic factors that targeted members of ActivinA/Nodal signaling pathway in preeclampsia placenta



Self-control of HGF regulation on trophoblast cell invasion and endothelial cell differentiation via modulating c-Met receptor expression and sheddin

 

Plain English:
  In mammalian, a successful pregnancy depends largely on the formation of placenta. Any defects in placenta development will lead to pregnancy-associated diseases, such as preeclampsia (PE), recurrent spontaneous abortion (RSA), intrauterine growth retardation (IUGR), etc. So far, our understanding of human placenta has been largely retarded.
  We are mainly interested in the regulatory mechanisms of human placenta development, pregnancy adaptation, as well as the pathogenesis of preeclampsia and RSA. Currently we are addressing: 1) the physiological coordination between the placenta and multiple maternal organs in response to pregnancy, also known as pregnancy adaptation. 2) the roles of preeclampsia biomarker-associated signalings in human placentation. 3) the interactions among the many cell types at the feto-maternal interface, to figure out the imbalanced immune regulation in the occurrence of preeclampsia and RSA. 4) development of reliable and specific molecular targets for early diagnosis and intervention of severe PE and RSA.
  Our long-term goal is to get better understanding on the regulation of placenta development and pregnancy adapatation, and to develop reliable strategies for early diagnosis and intervention of pregnancy-associated diseases.

 

Selected publications:

  1. Luo R, Wang Y, Xu P, Cao G, Zhao Y, Shao X, Li YX, Chang C, Peng C, Wang YL*. Hypoxia-inducible miR-210 contributes to preeclampsia via targeting thrombospondin type I domain containing 7A. Sci Rep. 2016, 6:19588
  2. Li S, Wang Y, Cao B, Wu Y, Ji L, Li YX, Liu M, Zhao Y, Qiao J, Wang H, Wang H, Han C, Wang YL*.Maturation of GDF15 in human placental trophoblast cells depends on the interaction with matrix metalloproteinase-26 (MMP-26). J Clin Endo Metab, 2014, 99(11):E2777-87
  3. Luo R, Shao X, Xu P, Liu Y, Wang Y, Zhao Y, Liu M, Ji L, Li YX, Chang C, Qiao J, Peng C*, Wang YL*. MicroRNA-210 contributes to preeclampsia by down-regulating KCMF1. Hypertension, 2014 64:839-847
  4. Xu P, Zhao Y, Liu M, Wang Y, Wang H, Li YX, Zhu X, Yao Y, Wang H, Qiao J, Ji L, Wang YL*. Variations of micrornas in human placentas and plasma from preeclamptic pregnancy. Hypertension, 2014, 63:1276-1284
  5. Ji L, Brkić J, Liu M, Fu G, Peng C*, Wang YL*. Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Asp Med, 2013,34:981-1023
  6. Yu L, Li D, Liao Q, Yang H, Cao B, Fu G, Ye G, Bai Y, Wang H, Cui N, Liu M, Li YX, Peng C, Wang YL*. High levels of ActivinA detected in preeclamptic placenta induce trophoblast cell apoptosis by promoting Nodal signaling. J Clin Endo Metab, 2012, 97: E1370–E1379
  7. Yang Y, Wang Y, Zeng X, Ma XJ, Zhao Y, Qiao J, Cao B,Li YX, Ji L, Wang YL*. Self-control of HGF regulation on human trophoblast cell invasion via enhancing c-Met receptor shedding by ADAM10 and ADAM17. J Clin Endo Metab, 2012, 97: E1390–E1401
  8. Gao WL, Liu M, Li D, Yang H, Liao Q, Yang Y, Bai Y, Li YX, Peng C, Wang YL*. The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1). RNA Biol, 2012, 9:1002-1010



dNK cell regulate trophoblast cell differentiation in a paracrine manner



Imbalanced production of placental steroid hormones trigger SerpinF2 upregulation and excessive hyper-coagulation in preeclampsia