Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages
Bibliographic record
Abstract
// Tanzil Ur Rahman 1, 2, * , Kamran Ullah 1, 2, 5, * , Meng-Xi Guo 1, 2 , Hai-Tao Pan 4 , Juan Liu 1 , Jun Ren 1, 2 , Lu-Yang Jin 1, 2 , Yu-Zhong Zhou 1, 2 , Yi Cheng 1, 2 , Jian-Zhong Sheng 1, 2, 3 and He-Feng Huang 1, 3 1 The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, China 2 Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China 3 The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 4 Shaoxing Women and Children's Hospital, Shaoxing, China 5 Department of Zoology, University of Swabi, Anbar, Khyber Pakhtunkhwa, Pakistan * These authors contributed equally to this work Correspondence to: Jian-Zhong Sheng, email: shengjz@zju.edu.cn He-Feng Huang, email: huanghefg@hotmail.com Keywords: androgen; recurrent miscarriage; PCOS Received: July 03, 2017 Accepted: March 02, 2018 Published: May 15, 2018 ABSTRACT High androgen level impairs endometrial receptivity in women experiences the recurrent miscarriage. The mechanism of androgen actions on endometrium is still uncertain. We hypothesized that androgen has a direct effect on the endometrium in women with recurrent miscarriage. In the present study, we assess the impact of androgen (A 2 ) at high concentration (10 –7 M) on Ishikawa cells compared with the physiological concentration of androgen (10 –9 M). To go into deeper analysis, we use global stable isotopes labeled profiling tactic using iTRAQ reagents, followed by 2D LC-MS/MS. We determine 175 non-redundant proteins, and 18 of these were quantified. The analysis of differentially expressed proteins (DEPs) identified 8 up-regulated proteins and 10 down-regulated in the high androgen group. These DEPs were examined by ingenuity pathway (IPA) analysis and established that these proteins might play vital roles in recurrent miscarriage and endometrium receptivity. In addition, proteins cyclin-dependent kinase inhibitor 2a (CDKN2a), endothelial protein C receptor (EPCR), armadillo repeat for velocardiofacial (ARVCF) were independently confirmed using western blot. Knockdown of CDKN2a significantly decreased the expression level of CDKN2a protein in ishikawa cells, and decreased migration ( p < 0.01), invasion ( p < 0.05), proliferation ( p < 0.05), and the rate of Jar spheroid attachment ( p < 0.05) to Ishikawa cell monolayer. The present results suggest that androgen at high concentration could alter the expression levels of proteins related to endometrium development and embryo implantation, which might be a cause of the impaired endometrial receptivity and miscarriage.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".