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

International Journal of Biological Sciences
Yanqing WuJian Xiao

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.

Citations

Dec 11, 2019·Journal of Animal Physiology and Animal Nutrition·Hong JiJianfa Wang
Jan 1, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Ayeh BoloukiHossein Bordbar
Jul 3, 2020·Hormones : International Journal of Endocrinology and Metabolism·Doina CreţuRaluca-Monica Pop
Sep 29, 2020·Systems Biology in Reproductive Medicine·Kosar Abbasi SamieMahsa Afrough
Oct 23, 2019·Molecular and Cellular Endocrinology·Li LiQing-Yuan Sun
Jan 8, 2021·Molecular Human Reproduction·Miyuki HaradaYutaka Osuga
Feb 6, 2021·Molecular Human Reproduction·Miyuki HaradaYutaka Osuga

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Methods Mentioned

BETA
Assay
protein assay
electrophoresis

Software Mentioned

Multi Gauge Software Science Lab
Graphpad Prism5

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis