Deputy Director, International Affairs Office
Master Supervisor, Zhejiang University School of Medicine
Associate Chief Physician, the Department of Reproductive Endocrinology

Education:

2016-2017   University of Wisconsin   Visiting Scholar

2009-2010   UBC, Canada            Visiting Scholar

2004-2007   Zhejiang University       Doctor Degree

1999-2001   Sichuan University        Master Degree

1994-1999   Sichuan University        Bachelor Degree

Expertise:

Reproductive endocrinology, early pregnancy maintenance

Research Interests:

Reproductive endocrinology, early pregnancy maintenance

Research Narrative:

Early pregnancy loss is the most common complication of human reproduction. Given the complexities of early development, it is likely that many mechanisms are involved. Knowledge of differences in protein expression is essential to understand the comprehensive pathophysiological mechanism underlying early pregnancy loss. My previous study had indicated several proteins that are associated with widespread failure in cell regulations and processes such as cellular stress response, cell structure, cell growth, metabolism and proteolysis at maternal-fetal interface of EPL, shedding a new insight into the proteins which may be potentially involved in the pathophysiological mechanisms underlying EPL.

Firstly, proteomic analysis was performed on decidua in women with EPL. Then, expression markers of ER stress, redox status, apoptotic features, and cell viabilities were analyzed in EPL decidual cells. In this study, we found that EPL decidual cells were characterized with decreased glucose-regulated protein 78 and valosin-containing protein expression levels, and burdened with the ubiquitinated proteins and elevated reactive oxygen species.  The evidences of ER stress-induced apoptosis in EPL decidual cells was shown by extensive dilation of ER, different morphological states of apoptosis, and the activation of caspase-4 and caspase-12, which further threatened cell viability and contributed to the dysfunction of EPL decidua. When exposed to additional H2O2, the EPL decidual cells were more vulnerable to OS challenge than the normal decidual cells. However, we found that the increased ubiquitinated proteins level and lowered cell viability induced by H2O2 in the normally decidual cells were remarkably attenuated in the presence of vitamin E. The sum of these observations indicates for the first time that sustained ER stress exists in EPL decidual cells, and the potentially vicious relationship between ER stress and OS is likely to play an important role in the development of EPL.

Furthermore, trophoblastic proliferation and differentiation in an orderly manner play a critical role in the placentation and maintenance of early pregnancy. The pathological mechanism underlying early pregnancy loss (EPL) is greatly related with poorly trophoblastic differentiation. My previous study on EPL chorionic tissues found that SGK1 expression level was significantly changed in trophoblastic cells of EPL when compared with the controls, which suggesting that SGK1 has an important role in early placental development and maintenance of pregnancy. In my future study, I aim to reveal the characteristics of spatial-temporal expression, regulative pattern and related molecular mechanisms during the development of trophoblastic cells, vascular remodeling and early pregnancy by using cellular co-culture system as a proliferation-differentiation model, combination with the in vitro gene control techniques and stress-induced mouse model. Ultimately, I aim to determinate the mechanism of vascular remodeling, pathologic mechanism of EPL, and provide valuable information and seek possible direction for cellular and molecular treatment.

Publication:

1. Wei-Hua He, Meng-Meng Jin, Ai-Ping Liu, Ying Zhou, Xiao-Ling Hu, Yi-Min Zhu, Ai-Xia Liu.Estradiol promotes trophoblast viability and invasion by activating SGK1. 2019 Jun 13;117:109092. doi: 10.1016/j.biopha.2019.109092.

2.You JL, Wang W, Tang MY, Ye YH, Liu AX, Zhu YM. A potential role of galectin-1 in promoting mouse trophoblast stem cell differentiation.Mol Cell Endocrinol. 2017 Nov 6. pii: S0303-7207(17)30568-3.

3.Tang M, You J, Wang W, Lu Y, Hu X, Wang C, Aixia Liu，Yimin Zhu. Impact of Galectin-1 on Trophoblast Stem cell Differenctialtion and Invasion in in Vitro Implantation Model，Reprod Sci. 2018 May;25(5):700-711.

4. Liu AX, Shi HY, Cai ZJ, Liu A, Zhang D, Huang HF, Jin HM. Increased risk of gonadal malignancy and prophylactic gonadectomy: a study of 102 phenotypic female patients with Y chromosome or Y-derived sequences.Hum Reprod. 2014;29(7):1413-9.

5. Liu AX, He WH, Yin LJ, Lv PP, Zhang Y, Sheng JZ, Leung PC, Huang HF. Sustained endoplasmic reticulum stress as a cofactor of oxidative stress in decidual cells from patients with early pregnancy loss[J]. J Clin Endocrinol Metab. 2011, 96(3): E493-7.

6. Ai-Xia Liu, Jian-hong Zhou, Hang-Mei Jin, Chang-kuen Zhu, Xiao-Duan Cheng.  Primary rhabdomyosarcoma of the urethra in an infantile woman: case report and literature review[J]. Urology. 2007, 69(6):1208.e17-9.

7.  Ai-Xia Liu, Yi-Min Zhu, Hui-Juan Gao, Xiao-Ming Zhu, Chen-Ming Xu, He-Feng Huang. Specific peptide patterns of follicular fluids at different growth stages analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry [J]. Biochimica et Biophysica Acta. 2007, 1770(1):29-38.

8. Ai-Xia Liu, Fan Jin, Tian-Hua Zhou, Cai-Yun Zhou, Wei-Miao Yao, Yu-Li Qian, He-Feng Huang. Proteomic analysis on the alteration of protein expression in the placental villous tissue of early pregnancy loss[J]. Biol Reprod, 2006, 75(3):414-420.

9. A. X. Liu, H. F. Huang, W. Y. Shen, J. Shen, C. M. Xu, X. Sheng. Peptide patterns of human follicular fluid analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) : biomarkers for follicle maturation? [abstract] Fertil Steril, 2005, 84(Suppl 1) : S158-S159.

10.  Ai-Xia Liu, Jin Shun, Wen-qun Shao, Hang-Mei Jin, Wei-Qin Song. Steroid cell tumors, not otherwise specified (NOS), in an accessory ovary: a case report and literature review[J]. Gynecol Oncol, 2005, 97（1）：260-262.

11.  Zou QY, Zhao YJ, Zhou C, Liu AX, Zhong XQ, Yan Q, Li Y, Yi FX, Bird IM, Zheng J. G Protein α Subunit 14 Mediates Fibroblast Growth Factor 2-Induced Cellular Responses in Human Endothelial Cells. J Cell Physiol. 2019 Jul;234(7):10184-10195. doi: 10.1002/jcp.27688. Epub 2018 Nov 1.

12.  Zou QY, Zhao YJ, Li H, Wang XZ, Liu AX, Zhong XQ, Yan Q, Li Y, Zhou C, Zheng J. GNA11 differentially mediates fibroblast growth factor 2- and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells. J Physiol. 2018 Jun;596(12):2333-2344. doi: 10.1113/JP275677. Epub 2018 May 12.

13.  Zhou C, Zou QY, Li H, Wang RF, Liu AX, Magness RR, Zheng J.Preeclampsia Downregulates MicroRNAs in Fetal Endothelial Cells: Roles of miR-29a/c-3p in Endothelial Function. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3470-3479. doi: 10.1210/jc.2017-00849. (IF=6.2)

14.  Yin LJ, Zhang Y, Lv PP, He WH, Wu YT, Liu AX, Ding GL, Dong MY, Qu F, Xu CM, Zhu XM, Huang HF .Insufficient maintenance DNA methylation is associated with abnormal embryonic development.BMC Med. 2012 Mar 13;10:26. doi: 10.1186/1741-7015-10-26.

15.  Gao HJ, Zhu YM, He WH, Ai-Xia Liu, Dong MY, Jin M, Sheng JZ, Huang HF.Endoplasmic reticulum stress induced by oxidative stress in decidual cells: a possible mechanism of early pregnancy loss[J]. Mol Biol Rep. 2012 Sep;39(9):9179-86.

16.  Zhang RJ, Zou LB, Zhang D, Tan YJ, Wang TT, Liu AX, Qu F, Meng Y, Ding GL, Lu YC, Lv PP, Sheng JZ, Huang HF.Functional expression of large-conductance calcium-activated potassium channels in human endometrium: a novel mechanism involved in endometrial receptivity and embryo implantation. J Clin Endocrinol Metab. 2012 Feb;97(2):543-53.

17.  Zou LB, Zhang RJ, Tan YJ, Ding GL, Shi S, Zhang D, He RH, Liu AX, Wang TT, Leung PC, Sheng JZ, Huang HF. Identification of estrogen response element in the aquaporin-2 gene that mediates estrogen-induced cell migration and invasion in human endometrial carcinoma[J].J Clin Endocrinol Metab, 2011, 96(9):E1399-408.

18.  Zhang Y, Zhang YL, Feng C, Wu YT, Liu AX, Sheng JZ, Cai J, Huang HF. Comparative proteomic analysis of human placenta derived from assisted reproductive technology. Proteomics. 2008 Oct;8(20):4344-56.

19.  Ruan HC, Zhu XM, Luo Q, Liu AX, Qian YL, Zhou CY, Jin F, Huang HF, Sheng JZ. Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice[J]. Hum Reprod. 2006, 21(10):2521-9.

20.  Xiu-E Lu, Wei-Xuan Ning, Ming-Yue Dong, Ai-Xia Liu, Fan Jin, He-Feng Huang. Vascular endothelial growth factor and matrix metalloproteinase-2 expedite formation of endometriosis in the early stage ICR mouse model[J]. Fertil Steril, 2006, 86 Suppl 4:1175-1181.

Personal Homepage:

https://person.zju.edu.cn/en/liuaixia