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Original Research Article | OPEN ACCESS

High androgen level causes recurrent miscarriage and impairs endometrial receptivity

Yan Su, Haofan Shi

Department of Gynecology and Obstetrics, International Peace Maternity & Child Health Hospital, Shanghai 200032, China;

For correspondence:-  Haofan Shi   Email: saukle@yahoo.com   Tel:+862164070434

Accepted: 22 June 2019        Published: 29 July 2019

Citation: Su Y, Shi H. High androgen level causes recurrent miscarriage and impairs endometrial receptivity. Trop J Pharm Res 2019; 18(7):1547-1552 doi: 10.4314/tjpr.v18i7.27

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of androgen (A2) at different concentrations on human endometrial epithelial cancer cell line (HHUA) using iTRAQ and liquid chromatography–mass spectrometry (LC-MS/MS) analysis.
Methods: Human endometrial cells were cultured in Dulbecco Modified Eagle Medium. Total protein was isolated from human endometrial cells and HHUA cells were treated with A2 in three different concentrations (10-9, 10-8 and 10-7 M). The proteins were digested using filter-aided sample preparation (FASP) method, and labeled using iTRAQ. The proteins were then subjected to LC-MS/MS. The resultant peptides were identified using Expasy tool, and the up-stream and down-stream proteins were confirmed. Moreover, the up-regulated proteins: isoform 2 of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1), isoform 2 of endothelial differentiation-related factor 1 (EDF1), and acid phosphatase 1 (ACP1) were independently confirmed using western blotting and immunohistochemistry techniques.
Results: Transforming growth factor (TGF), p38 mitogen-activated protein kinase (p38-MAPK), cyclin-dependent kinase (CDK), and tumor protein p53 (TP53) were the major regulators of the upstream process, and were upregulated RM-linked endometrial epithelial cells. Androgen-associated proteins NUCKS1, EDF1, and ACP1 were significantly responsible for miscarriage-related changes in endometrial tissues (p < 0.05). The results showed that a high level of androgen significantly (p < 0.05) distorts the expression levels of proteins associated with endometrium development, resulting in impaired endometrial accessibility which led to miscarriage.
Conclusion: Androgen-associated proteins are responsible for changes in endometrial tissues which, in turn, lead to recurrent miscarriage.

Keywords: Recurrent miscarriage, Human endometrial cells, Polycystic ovarian syndrome, iTRAQ analysis, Androgens

Impact Factor
Thompson Reuters (ISI): 0.523 (2021)
H-5 index (Google Scholar): 39 (2021)

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