Necroptosis in stressed ovary

Abstract

Stress is deeply rooted in the modern society due to limited resources and large competition to achieve the desired goal. Women are more frequently exposed to several stressors during their reproductive age that trigger generation of reactive oxygen species (ROS). Accumulation of ROS in the body causes oxidative stress (OS) and adversely affects ovarian functions. The increased OS triggers various cell death pathways in the ovary. Beside apoptosis and autophagy, OS trigger necroptosis in granulosa cell as well as in follicular oocyte. The OS could activate receptor interacting protein kinase-1(RIPK1), receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) to trigger necroptosis in mammalian ovary. The granulosa cell necroptosis may deprive follicular oocyte from nutrients, growth factors and survival factors. Under these conditions, oocyte becomes more susceptible towards OS-mediated necroptosis in the follicular oocytes. Induction of necroptosis in encircling granulosa cell and oocyte may lead to follicular atresia. Indeed, follicular atresia is one of the major events responsible for the elimination of majority of germ cells from cohort of ovary. Thus, the inhibition of necroptosis could prevent precautious germ cell depletion from ovary that may cause reproductive senescence and early menopause in several mammalian species including human.

Advanced Oxidation Protein Products Induce G1/G0‐Phase Arrest in Ovarian Granulosa Cells via the ROS‐JNK/p38 MAPK‐p21 Pathway in Premature Ovarian Insufficiency

“…Granulosa cells play a crucial role in ovarian function maintenance, and suppression of granulosa cell proliferation contributes to POI development [ 38 ]. Follicular development relies on orchestrated crosstalk between oocytes and granulosa cells [ 39 ]; thus, proliferation inhibition in granulosa cells may deprive follicular oocytes of nutrients, growth factors, and survival factors [ 40 ]. In addition, dysfunction of granulosa cells can result in follicular atresia, the major event responsible for oocyte elimination, leading to the onset of POI.…”

Women with polycystic ovary syndrome (PCOS) have reduced melatonin concentrations in their follicles and have mild sleep disturbances

“…Oxidation-antioxidant balance plays an important role in oocyte maturation. Physiological level of reactive oxygen species (ROS) can be used as the second messenger of genes related to oocyte maturation to regulate the function of oocytes, but excessive accumulation of ROS can cause oxidative stress, which will adversely affect ovarian function [ 31 ]. In the ovary, this antioxidant plays a variety of roles, such as inhibiting cell apoptosis, reducing autophagy to improve mitochondrial function, and maintaining telomeres to delay ovarian senescence [ 32 – 34 ].…”

Review of psychological stress on oocyte and early embryonic development in female mice

“…Recent studies have indicated that the generation of OS because of ROS accumulation, which reduces oestradiol-17β biosynthesis in the ovaries, triggers apoptosis in most granulosa cells and disrupts the developing follicular oocytes [ 78 ]. OS can also trigger necroptosis, an unregulated cell death, in granulosa cells and follicular oocytes [ 83 ]. Excessive TNF-α attenuated ovarian development by reducing the number of mature follicles and disrupting oocyte meiotic maturation in mice [ 84 ].…”