Necrosis and necroptosis in germ cell depletion from mammalian ovary

Abstract

The maximum number of germ cells is present during the fetal life in mammals. Follicular atresia results in rapid depletion of germ cells from the cohort of the ovary. At the time of puberty, only a few hundred (<1%) germ cells are either culminated into oocytes or further get eliminated during the reproductive life. Although apoptosis plays a major role, necrosis as well as necroptosis, might also be involved in germ cell elimination from the mammalian ovary. Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise. Necroptosis is initiated by tumor necrosis factor and operated through receptor interacting protein kinase as well as mixed lineage kinase domain‐like protein. The acetylcholinesterase, cytokines, starvation, and oxidative stress play important roles in necroptosis‐mediated granulosa cell death. The granulosa cell necroptosis directly or indirectly induces susceptibility toward necroptotic or apoptotic cell death in oocytes. Indeed, prevention of necrosis and necroptosis pathways using their specific inhibitors could enhance growth/differentiation factor‐9 expression, improve survivability as well as the meiotic competency of oocytes, and prevent decline of reproductive potential in several mammalian species and early onset of menopause in women. This study updates the information and focuses on the possible involvement of necrosis and necroptosis in germ cell depletion from the mammalian ovary.

Pyroptosis: A New Regulating Mechanism in Cardiovascular Disease

“…Cell lysis releases inclusions and often causes an inflammatory response; the healing process is often accompanied by fibrosis of tissues and organs, resulting in scarring. 10 , 11 …”

Endoplasmic Reticulum Stress during Mammalian Follicular Atresia

“…Necroptosis contributes to follicular atresia and luteolysis [102]. The factors involved in granulosa cell necroptosis can be regulated by acetylcholinesterase (AChE), cytokines, starvation, and oxidative stress via TNFα [103]. Also, an ovarian AChE variant, the read-through isoform AChE-R, has a nonenzymatic function that stimulates RIPK1-/MLKL-dependent necroptosis [103].…”

“…The factors involved in granulosa cell necroptosis can be regulated by acetylcholinesterase (AChE), cytokines, starvation, and oxidative stress via TNFα [103]. Also, an ovarian AChE variant, the read-through isoform AChE-R, has a nonenzymatic function that stimulates RIPK1-/MLKL-dependent necroptosis [103]. Therefore, although the participation of the ER in necroptosis and the contribution of this PCD in follicular atresia have been shown, the interrelation between ER stress-induced necroptosis and follicular atresia is completely unknown.…”

The Impact of Aging on Macroautophagy in the Pre-ovulatory Mouse Oocyte

“…It should be noted that autophagy can fulfill dual roles in the ovary, whereby it is not only responsible for promoting oocyte survival but alternatively, can promote cell death. Indeed, autophagy pathways operating alongside other cell death mechanisms, such as apoptosis and necroptosis, have been implicated in follicular atresia, an important mechanism responsible for oocyte loss with increasing age ( Escobar et al, 2008 ; Yadav et al, 2018 ; Chaudhary et al, 2019 ).…”