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Published on: February 3, 2017
Autophagy in hypoxic ovary
Anil Kumar Yadav1, Pramod K Yadav1, Govind R Chaudhary1
1Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
Abstract:
Oxygen deprivation affects human health by modulating system as well as cellular physiology. Hypoxia generates reactive oxygen species (ROS), causes oxidative stress and affects female reproductive health by altering ovarian as well as oocyte physiology in mammals. Hypoxic conditions lead to several degenerative changes by inducing various cell death pathways like autophagy, apoptosis and necrosis in the follicle of mammalian ovary. The encircling somatic cell death interrupts supply of nutrients to the oocyte and nutrient deprivation may result in the generation of ROS. Increased level of ROS could induce granulosa cells as well as oocyte autophagy. Although autophagy removes damaged proteins and subcellular organelles to maintain the cell survival, irreparable damages could induce cell death within intra-follicular microenvironment. Hypoxia-induced autophagy is operated through 5' AMP activated protein kinase-mammalian target of rapamycin, endoplasmic reticulum stress/unfolded protein response and protein kinase C delta-c-junN terminal kinase 1 pathways in a wide variety of somatic cell types. Similar to somatic cells, we propose that hypoxia may induce granulosa cell as well as oocyte autophagy and it could be responsible at least in part for germ cell elimination from mammalian ovary. Hypoxia-mediated germ cell depletion may cause several reproductive impairments including early menopause in mammals.
Insights
Hypoxia, or oxygen deprivation, triggers cell death pathways in the mammalian ovary, impacting female reproductive health. This study suggests hypoxia-induced autophagy contributes to germ cell loss, potentially causing early menopause.
Area of Science:
- Reproductive Biology
- Cellular Physiology
- Oxidative Stress Research
Background:
- Oxygen deprivation (hypoxia) significantly impacts systemic and cellular physiology.
- Hypoxia induces reactive oxygen species (ROS) and oxidative stress, negatively affecting female reproductive health, specifically ovarian and oocyte physiology.
- Degenerative changes in the mammalian ovary, including cell death pathways like autophagy, apoptosis, and necrosis, are observed under hypoxic conditions.
Purpose of the Study:
- To investigate the role of hypoxia-induced autophagy in mammalian ovarian germ cell elimination.
- To explore the potential link between hypoxia-mediated germ cell depletion and reproductive impairments such as early menopause.
Main Methods:
- Review of existing literature on hypoxia, oxidative stress, and autophagy in mammalian ovarian cells.
- Analysis of proposed signaling pathways (AMPK-mTOR, ER stress/UPR, PKCδ-JNK1) involved in hypoxia-induced autophagy.
- Hypothesized mechanisms of nutrient deprivation and ROS generation impacting granulosa cells and oocytes.
Main Results:
- Hypoxia induces various cell death pathways, including autophagy, apoptosis, and necrosis, within the ovarian follicle.
- Somatic cell death disrupts nutrient supply to the oocyte, potentially generating ROS and inducing autophagy in granulosa cells and oocytes.
- Hypoxia-induced autophagy in ovarian cells may be mediated by conserved signaling pathways observed in somatic cells.
Conclusions:
- Hypoxia-induced autophagy in granulosa cells and oocytes is proposed as a significant factor in germ cell elimination from the mammalian ovary.
- Hypoxia-mediated germ cell depletion could be a contributing cause of reproductive impairments, including premature menopause.
- Understanding these mechanisms is crucial for addressing female reproductive health issues related to oxygen deprivation.
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