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Int J Biol Sci 2017; 13(10):1297-1308. doi:10.7150/ijbs.21172

Research Paper

Diabetes Induces Abnormal Ovarian Function via Triggering Apoptosis of Granulosa Cells and Suppressing Ovarian Angiogenesis

Yanqing Wu1*✉, Yiyang Li2*, Xinghui Liao3*, Zhengchao Wang4, Rui Li2, Shuang Zou2, Ting Jiang2, Bingbing Zheng5, Ping Duan6, Jian Xiao2✉

1. The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China;
2. Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;
3. Department of Molecular Pathology Laboratory, Zhejiang Rongjun Hospital, Jiaxing Zhejiang 314000;
4. College of Life Sciences, Fujian Normal University,Fuzhou 350007, China;
5. Department of Obstetrics, First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China;
6. Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
* These authors contributed equally to this work.

Abstract

Diabetes triggers abnormal ovarian follicular development and consequently leads to infertility. Here, we established a type 2 diabetes mouse model by feeding with high fat diet (HFD) for 15/20 weeks and assessed the effect of diabetes on follicular development and ovarian angiogenesis. After fed with HFD for 15 weeks, mice had the characteristics of type 2 diabetes, which was much more serious after 20 weeks on HFD. After 20 weeks on HFD, the mice had shown abnormal ovarian morphology with hyaline appearance, much less blood vessel, follicular development arrest and less of granulosa cells (GCs) in mature follicles, but not in ovaries from 15 weeks on HFD. Elevated makers of DNA damage, ER stress and apoptosis of GCs were observed in ovaries from HFD for 20 weeks. Additionally, diabetes significantly suppressed ovarian angiogenesis with the evidence of down-regulation of CD31 via inhibiting HIF1α-VEGF signaling pathway in time-dependent. We concluded that diabetes triggers abnormal ovarian function via inducing GCs apoptosis and suppressing ovarian angiogenesis.

Keywords: diabetes, granulosa cells (GCs), apoptosis, angiogenesis, DNA damage.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wu Y, Li Y, Liao X, Wang Z, Li R, Zou S, Jiang T, Zheng B, Duan P, Xiao J. Diabetes Induces Abnormal Ovarian Function via Triggering Apoptosis of Granulosa Cells and Suppressing Ovarian Angiogenesis. Int J Biol Sci 2017; 13(10):1297-1308. doi:10.7150/ijbs.21172. Available from http://www.ijbs.com/v13p1297.htm