Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 237, Issue 2, Pages 1157-1170Publisher
WILEY
DOI: 10.1002/jcp.30613
Keywords
apoptosis; autophagy; cell death; follicular development; marker genes; ovary
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Follicular development and maintenance of the primordial follicle pool play a crucial role in the reproductive lifespan of an organism, with autophagy serving as a key regulatory mechanism. Dysregulation or mutation of autophagy-related genes can significantly impact follicular development and, consequently, female reproductive health. Various signaling pathways are involved in regulating autophagy in granulosa and oocytes, with mTOR signaling being a primary mechanism.
The reproductive life span of the organism mainly depends on follicular development that maintains the primordial follicle pool in the cohort of follicles within the ovary. The total count of primordial follicles decreases with age due to ovulation and follicular atresia. Follicular atresia, a process of ovarian follicles degradation, mainly occurs via apoptosis, but recent studies also favor autophagy existence. Autophagy is a cellular and energy homeostatic response that helps to maintain the number of healthy primordial follicles, germ cell survival, and removal of corpus luteum remnants. But the excessive autophagic cell death changes both the quality and quantity of oocytes that ultimately affect female reproductive health. Autophagy regulation occurs by various autophagy-regulated genes like BECN1 and LC3-II (autophagy marker genes). Their abnormal regulation or mutation highly influences follicular development by alteration of primordial follicles formation, the decline in oocytes count, and germ cell loss. Various classical signaling pathways such as PI3K/AKT/mTOR, MAPK/ERK1/2, AMPK, and IRE1 are involved in granulosa and oocytes autophagy, while mTOR signaling is the primary mechanism. Along with basal level autophagy, chemical/hormone/stress-mediated autophagy also affects follicular development and female reproduction. In this review, we have primarily focused on granulosa cell and oocytes' autophagy, mechanism, and the role of autophagy determining marker genes in follicular development.
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