Uterine Insulin Sensitivity Defects Induced Embryo Implantation Loss Associated with Mitochondrial Dysfunction-Triggered Oxidative Stress.

Abstract

METHODS AND RESULTS:

Herein, a comprehensive proteomic analysis was conducted on proliferative endometria from sows with low and normal reproductive performance (LRP and NRP, respectively). Enrichment analysis of differentially expressed proteins revealed alterations in endometrial remodeling, substance metabolism (mainly lipid, nitrogen, and retinol metabolism), immunological modulation, and insulin signaling in LRP sows. Importantly, aberrant lipid metabolite accumulation and dysregulation of insulin signaling were coincidently confirmed in endometria of LPR sows, proving an impaired insulin sensitivity. Furthermore, established high-fat diet- (HFD-) induced insulin-resistant mouse models revealed that uterine insulin resistance beginning before pregnancy deteriorated uterine receptivity and decreased implantation sites and fetal numbers. Mitochondrial biogenesis and fusion were decreased, and reactive oxygen species was overproduced in uteri from the HFD group during the implantation period. Ishikawa and JAR cells directly demonstrated that oxidative stress compromised implantation in vitro.

CONCLUSIONS:

This study demonstrated that uterine insulin sensitivity impairment beginning before pregnancy resulted in implantation and fetal loss associated with oxidative stress induced by mitochondrial dysfunction.

• Authors: Meixia Chen, Jie Li, Bo Zhang, Xiangfang Zeng, Xiangzhou Zeng, Shuang Cai, Qianhong Ye, Guangxin Yang, Changchuan Ye, Lijun Shang, Shiyan Qiao
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 6655685 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 33953835 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Meixia Chen et al.

Chemical References

• Insulin

Topics

• Animals
• Embryo Implantation (physiology)
• Female
• Insulin (metabolism)
• Mice
• Mitochondria (metabolism)
• Oxidative Stress (physiology)
• Pregnancy
• Uterus (metabolism)