The Immp2l mutation causes ovarian aging through ROS-Wnt/ β-catenin-estrogen pathway: preventive effect of melatonin.

The Immp2l mutation causes ovarian aging through ROS-Wnt/β-catenin-estrogen pathway: preventive effect of melatonin. Endocrinology. 2020 Jul 11;: Authors: He Q, Gu L, Lin Q, Ma Y, Liu C, Pei X, Li PA, Yang Y Abstract Mitochondria play important roles in ovarian follicle development. Mitochondrial dysfunction, including mitochondrial gene deficiency, impairs the ovarian development. Here, we explored the role and mechanism of mitochondrial inner membrane gene Immp2l in ovarian follicle growth and development. Our results revealed that the female Immp2l-/- mice were infertile, while the Immp2l+/- mice were normal. Body and ovarian weights were reduced in the female Immp2l-/- mice, ovarian follicle growth and development were stunted in the secondary follicle stage. Although a few ovarian follicles were ovulated, the oocytes were not fertilized due to mitochondrial dysfunction. Increased oxidative stress, decreased estrogen levels, and altered genes expression of Wnt/β-catenin and steroid hormone synthesis pathways were observed in 28-day-old Immp2l-/- mice. The Immp2l mutation accelerated ovarian aging process, as no ovarian follicles were detected in age of 5 months in Immp2l-/- mice. All the aforementioned changes in the Immp2l-/- mice were reversed by administration of antioxidant melatonin to the Immp2l-/- mice. Furthermore, our in vitro study using Immp2l knockdown granulosa cells confirmed that the Immp2l downregulation induced...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research