Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia

Li,Runqin; Wu,Juan; He,Junlin; Wang,Yingxiong; Liu,Xueqing; Chen,Xuemei; Tong,Chao; Ding,Yubin; Su,Yan; Chen,Wenqi; Zhang,Chen; Gao,Rufei

doi:10.3892/mmr.2017.6322

Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia

Authors:
- Runqin Li
- Juan Wu
- Junlin He
- Yingxiong Wang
- Xueqing Liu
- Xuemei Chen
- Chao Tong
- Yubin Ding
- Yan Su
- Wenqi Chen
- Chen Zhang
- Rufei Gao
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Affiliations: Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400014, P.R. China, Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: March 14, 2017 https://doi.org/10.3892/mmr.2017.6322
Pages: 2503-2510
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have investigated the lower embryo implantation rates in women with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the association between the abnormal oocyte and embryo and hyperinsulinemia. The importance of hyperinsulinemia on maternal endometrium receptivity remains to be elucidated. The present study used a hyperinsulinemic mouse model to determine whether hyperinsulinemia may affect endometrial receptivity. An insulin intervention mouse model was first established. The serum levels of insulin, progesterone and estradiol were subsequently detected by ELISA assay analysis. The number of implantation sites was recorded using Trypan blue dye and the morphology of mice uteri was investigated using hematoxylin and eosin staining. The expression levels of molecular markers associated with endometrial receptivity were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry analyses. Finally, the importance of mechanistic target of rapamycin (mTOR) expression following insulin treatment was determined. Mice treated with insulin developed insulin resistance and hyperinsulinemia. The number of implantation sites following insulin treatment did not differ between the control and insulin‑treated groups. Additionally, no significant morphological alterations in mice uteri between control and insulin‑treated groups were observed. However, the expression levels of estrogen receptor (Esr) 1, Esr2, progesterone receptor and homeobox A10 associated with endometrial receptivity, were imbalanced during endometrium receptivity when maternal hyperinsulinemia was induced. Western blot analysis revealed that expression levels of endometrial phosphorylated (p)‑mTOR and p‑ribosomal protein S6 kinase β‑1 were significantly greater in the insulin‑treated group. These results demonstrated that although an embryo may implant into endometrium, mice endometrium receptivity in early pregnancy may be impaired by maternal hyperinsulinemia. In addition, mTOR signaling may be involved in this process. The present study provides preliminary results demonstrating that female reproduction may be compromised during hyperinsulinemia, which requires further investigation in future studies.

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