High androgen level causes recurrent miscarriage and impairs endometrial receptivity

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 (LCMS/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 cyclindependent 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), cyclindependent 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.

Atractylenolide promotes trophoblast cell proliferation and migration in recurrent spontaneous abortion via ERK pathway

“…Recurrent spontaneous abortion (RSA) occurs in 2 -5 % of women of childbearing age [1]. The main cause of RSA are immune regulatory protein defects, stressful life events, psychological trauma, smoking and alcohol consumption, infection, environmental factors, genetics, and hormonal abnormalities are considered to be the main causes of RSA [2].…”