Follicular oocyte as a potential target for severe acute respiratory syndrome coronavirus 2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019 and rapidly became a pandemic as coronavirus disease 2019 (COVID-19). Apart from other organs, presence of specific receptor angiotensin-converting enzyme (ACE2) and corresponding proteases such as transmembrane serine protease 2, basigin and cysteine protease cathepsin L make follicular somatic cells as well as oocyte as potential targets for SARS-CoV-2 infection. The SARS-CoV-2 causes inflammation and hypoxia that generate reactive oxygen species (ROS) in critically ill patients. In addition, a large number of casualties and insecurity of life due to repeated waves of SARS-CoV-2 infection generate psychological stress and cortisol resulting in the further generation of ROS. The excess levels of ROS under physiological range cause meiotic instability, while high levels result in oxidative stress that trigger various death pathways and affect number as well as quality of follicular oocytes. Although, emerging evidence suggests that the SARS-CoV-2 utilises cellular machinery of ovarian follicular cells, generates ROS and impairs quality of follicular oocytes, the underlying mechanism of viral entry into host cell and its negative impact on the follicular oocyte remains poorly understood. Therefore, this review summarises emerging evidence on the presence of cellular machinery for SARS-CoV-2 in ovarian follicles and the potential negative impact of viral infection on the follicular oocytes that affect ovarian functions in critically ill and stressed women.

Emerging Role of Autophagy in Governing Cellular Dormancy, Metabolic Functions, and Therapeutic Responses of Cancer Stem Cells.

Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.

Regulation of metastatic potential by drug repurposing and mitochondrial targeting in colorectal cancer cells.

BACKGROUND: Increased mitochondrial activities contributing to cancer cell proliferation, invasion, and metastasis have been reported in different cancers; however, studies on the therapeutic targeting of mitochondria in regulating cell proliferation and invasiveness are limited. Because mitochondria are believed to have evolved through bacterial invasion in mammalian cells, antibiotics could provide an alternative approach to target mitochondria, especially in cancers with increased mitochondrial activities. In this study, we investigated the therapeutic potential of bacteriostatic antibiotics in regulating the growth potential of colorectal cancer (CRC) cells, which differ in their metastatic potential and mitochondrial functions. METHODS: A combination of viability, cell migration, and spheroid formation assays was used to measure the effect on metastatic potential. The effect on mitochondrial mechanisms was investigated by measuring mitochondrial DNA copy number by qPCR, biogenesis (by qPCR and immunoblotting), and functions by measuring reactive oxygen species, membrane potential, and ATP using standard methods. In addition, the effect on assembly and activities of respiratory chain (RC) complexes was determined using blue native gel electrophoresis and in-gel assays, respectively). Changes in metastatic and cell death signaling were measured by immunoblotting with specific marker proteins and compared between CRC cells. RESULTS: Both tigecycline and tetracycline effectively reduced the viability, migration, and spheroid-forming capacity of highly metastatic CRC cells. This increased sensitivity was attributed to reduced mtDNA content, mitochondrial biogenesis, ATP content, membrane potential, and increased oxidative stress. Specifically, complex I assembly and activity were significantly inhibited by these antibiotics in high-metastatic cells. Significant down-regulation in the expression of mitochondrial-mediated survival pathways, such as phospho-AKT, cMYC, phospho-SRC, and phospho-FAK, and upregulation in cell death (apoptosis and autophagy) were observed, which contributed to the enhanced sensitivity of highly metastatic CRC cells toward these antibiotics. In addition, the combined treatment of the CRC chemotherapeutic agent oxaliplatin with tigecycline/tetracycline at physiological concentrations effectively sensitized these cells at early time points. CONCLUSION: Altogether, our study reports that bacterial antibiotics, such as tigecycline and tetracycline, target mitochondrial functions specifically mitochondrial complex I architecture and activity and would be useful in combination with cancer chemotherapeutics for high metastatic conditions.

Reactive oxygen species signalling in the deterioration of quality of mammalian oocytes cultured in vitro: Protective effect of antioxidants.

The in vitro fertilization (IVF) is the first choice of infertile couples worldwide to plan for conception. Besides having a significant advancement in IVF procedure, the success rate is still poor. Although several approaches have been tested to improve IVF protocol, minor changes in culture conditions, physical factors and/or drug treatment generate reactive oxygen species (ROS) in oocytes. Due to large size and huge number of mitochondria, oocyte is more susceptible towards ROS-mediated signalling under in vitro culture conditions. Elevation of ROS levels destabilize maturation promoting factor (MPF) that results in meiotic exit from diplotene as well as metaphase-II (M-II) arrest in vitro. Once meiotic exit occurs, these oocytes get further arrested at metaphase-I (M-I) stage or metaphase-III (M-III)-like stage under in vitro culture conditions. The M-I as well as M-III arrested oocytes are not fit for fertilization and limits IVF outcome. Further, the generation of excess levels of ROS cause oxidative stress (OS) that initiate downstream signalling to initiate various death pathways such as apoptosis, autophagy, necroptosis and deteriorates oocyte quality under in vitro culture conditions. The increase of cellular enzymatic antioxidants and/or supplementation of exogenous antioxidants in culture medium protect ROS-induced deterioration of oocyte quality in vitro. Although a growing body of evidence suggests the ROS and OS-mediated deterioration of oocyte quality in vitro, their downstream signalling and related mechanisms remain poorly understood. Hence, this review article summarizes the existing evidences concerning ROS and OS-mediated downstream signalling during deterioration of oocyte quality in vitro. The use of various antioxidants against ROS and OS-mediated impairment of oocyte quality in vitro has also been explored in order to increase the success rate of IVF during assisted reproductive health management.

Comparative Assessment of the Efficacy of Newly Designed Multiple Variability Loop and Opus Loop for Anterior en Masse Retraction in Orthodontics: A Finite Element Study.

Introduction Two different mechanisms are used to close the space after extractions, i.e., friction/sliding mechanics and frictionless/loop mechanics. The focus of this study is on space closure using frictionless or loop mechanics, which utilize loops to achieve the desired tooth movement. Loops are designed to increase the resiliency of the archwire so that the ideal moment-to-force ratio (M/F) of 8:1 to 10:1 for bodily tooth movement can be obtained. By incorporating various loop designs, the resiliency of archwires may be increased, and an ideal M/F ratio can be obtained. Method Different pre-activation bends were incorporated in the titanium molybdenum alloy (TMA) wire at alpha (canine side) and beta (premolar side), respectively. A total of 36 finite element method (FEM) models were prepared with and without pre-activation bends to evaluate the moment-to-force ratio. Result The results obtained from the finite element method (FEM) analysis provided valuable insights into the force and moment generated during activation while retracting the tooth. Specifically, the alpha bend at 15 degrees and the beta bend at 20 degrees produced the most desirable results for generating moments on the anterior and posterior teeth, respectively. Conclusion To ensure the proper utilization of the multiple variability (MV) loop, we recommend its preparation using a 0.019 x 0.025-inch TMA wire. This selection will maximize the loop's capabilities and enhance its performance in achieving the desired tooth movement.

Erratum: [Corrigendum] Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells.

[This corrects the article DOI: 10.3892/ol.2020.12176.].

Analysis of cellular and cell free mitochondrial DNA content and reactive oxygen species levels in maternal blood during normal pregnancy: a pilot study.

BACKGROUND: Alterations in mitochondrial signatures such as mitochondrial DNA (mtDNA) content in maternal blood have been linked to pregnancy-related complications. However, changes in maternal mtDNA content, their distribution and associated signaling during normal pregnancies are not clear; which could suggest their physiological role in maternal adaptation to pregnancy related changes and a reference threshold. THE AIM OF THIS STUDY: to assess the distribution of mtDNA in peripheral blood and their association with circulatory ROS levels across different trimesters of healthy pregnancy. METHODS: In this pilot cross sectional study, blood samples of normal pregnant women from each trimester (total = 60) and age-matched non-pregnant (NP) women as control group (n = 20) were analyzed for a) the relative distribution of mtDNA content in cellular and cell free (plasma) fractions using relative quantitative polymerase chain reaction (qPCR) and b) the levels of circulating reactive oxygen species (ROS) by measurement of plasma H2O2. The results were compared between pregnant and NP groups and within trimesters for significant differences, and were also analyzed for their correlation between groups using statistical methods. RESULTS: While, we observed a significant decline in cellular mtDNA; plasma mtDNA was significant increased across all trimesters compared to NP. However, from comparisons within trimesters; only cellular mtDNA content in 3rd trimester was significantly reduced compared to 1st trimester, and plasma mtDNA did not differ significantly among different trimesters. A significantly higher level of plasma H2O2 was also observed during 3rd trimester compared to NP and to 1st trimester. Correlation analysis showed that, while cellular mtDNA content was negatively correlated to plasma mtDNA and to plasma H2O2 levels; plasma mtDNA was positively correlated with plasma H2O2 content. CONCLUSIONS: This study suggested that normal pregnancy is associated with an opposing trend of reduced cellular mtDNA with increased circulatory mtDNA and H2O2 levels, which may contribute to maternal adaptation, required during different stages of pregnancy. Estimation of mtDNA distribution and ROS level in maternal blood could show mitochondrial functionality during normal pregnancy, and could be exploited to identify their prognostic/ diagnostic potential in pregnancy complications.

Approach to management of nerve gaps in peripheral nerve injuries.

Peripheral nerve injuries (PNI) are a major clinical problem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma (gunshot wounds) and stretching or crushing trauma and fractures. They can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Currently, the standard surgical technique for complete nerve transection is end-to-end neurorrhaphy. Unfortunately, there is segmental loss of the nerve trunk in some cases where nerve mobilization may permit end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. But in light of limited availability and concerned donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers and end-to-side neurorrhaphy. This review intends to present an overview of the literature on the applications of these techniques in repair of peripheral nerve injuries. This article also focuses on preoperative assessment, surgical timing, available options and future perspectives.

Lipid Metabolism and Mitochondria: Cross Talk in Cancer.

Metabolic reprogramming is considered a major event in cancer initiation, progression and metastasis. The metabolic signature of cancer cells includes alterations in glycolysis, mitochondrial respiration, fatty acid/lipid and amino acid metabolism. Being at a junction of various metabolic pathways, mitochondria play a key role in fueling cancer growth through regulating bioenergetics, metabolism and cell death. Increasing evidence suggests that alteration in lipid metabolism is a common feature of metastatic progression, including fatty acid synthesis as well as fatty acid oxidation. However, the interplay between lipid metabolism and mitochondria in carcinogenesis remains obscure. The present review focuses on key lipid metabolic pathways associated with mitochondrial regulation that drive cancer phenotype and metastasis. We also review potential targets of lipid metabolism and mitochondria to improve the therapeutic regime in cancer patients. This review aims to improve our current understanding of the intricate relation of lipids with mitochondria and provides insights into new therapeutic approaches.

Meiotic Instability Generates a Pathological Condition in Mammalian Ovum.

Maintenance of metaphase-II (M-II) arrest in ovum is required to present itself as a right gamete for successful fertilization in mammals. Surprisingly, instability of meiotic cell cycle results in spontaneous exit from M-II arrest, chromosomal scattering and incomplete extrusion of second polar body (PB-II) without forming pronuclei so called abortive spontaneous ovum activation (SOA). It remains unclear what causes meiotic instability in freshly ovulated ovum that results in abortive SOA. We propose the involvement of various signal molecules such as reactive oxygen species (ROS), cyclic 3',5' adenosine monophosphate (cAMP) and calcium (Ca2+) in the induction of meiotic instability and thereby abortive SOA. These signal molecules through their downstream pathways modulate phosphorylation status and activity of cyclin dependent kinase (cdk1) as well as cyclin B1 level. Changes in phosphorylation status of cdk1 and its activity, dissociation and degradation of cyclin B1 destabilize maturation promoting factor (MPF). The premature MPF destabilization and defects in other cell cycle regulators possibly cause meiotic instability in ovum soon after ovulation. The meiotic instability results in a pathological condition of abortive SOA and deteriorates ovum quality. These ova are unfit for fertilization and limit reproductive outcome in several mammalian species including human. Therefore, global attention is required to identify the underlying causes in greater details in order to address the problem of meiotic instability in ova of several mammalian species icluding human. Moreover, these activated ova may be used to create parthenogenetic embryonic stem cell lines in vitro for the use in regenerative medicine.Graphical abstract.

Critical role of three-dimensional tumorsphere size on experimental outcome.

Three-dimensional in vitro spheroids are a reliable model to study tumor biology and drug toxicity. However, inconsistencies exist in terms of seeding cell density that governs spheroid size and shape, influencing the experimental outcome. We investigated the effect of varying cell densities using glioblastoma cells on tumorsphere formation and their responsiveness to drug treatment. Our results demonstrated that in comparison with spheroids formed with lower cell density, spheroids formed with higher cell density were not only larger in size but also had a larger necrotic core surrounded by a higher number of quiescent cells and were irresponsive to drug treatment. Our study highlights the importance of predetermination of cell density to obtain desired/appropriate spheroid size to produce consistent and reliable data on drug toxicity studies in tumor cells.

Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells.

Mitochondria serve a vital role in cellular homeostasis as they regulate cell proliferation and death pathways, which are attributed to mitochondrial bioenergetics, free radicals and metabolism. Alterations in mitochondrial functions have been reported in various diseases, including cancer. Colorectal cancer (CRC) is one of the most common metastatic cancer types with high mortality rates. Although mitochondrial oxidative stress has been associated with CRC, its specific mechanism and contribution to metastatic progression remain poorly understood. Therefore, the aims of the present study were to investigate the role of mitochondria in CRC cells with low and high metastatic potential and to evaluate the contribution of mitochondrial respiratory chain (RC) complexes in oncogenic signaling pathways. The present results demonstrated that cell lines with low metastatic potential were resistant to mitochondrial complex I (C-I)-mediated oxidative stress, and had C-I inhibition with impaired mitochondrial functions. These adaptations enabled cells to cope with higher oxidative stress. Conversely, cells with high metastatic potential demonstrated functional C-I with improved mitochondrial function due to coordinated upregulation of mitochondrial biogenesis and metabolic reprogramming. Pharmacological inhibition of C-I in high metastatic cells resulted in increased sensitivity to cell death and decreased metastatic signaling. The present findings identified the differential regulation of mitochondrial functions in CRC cells, based on CRC metastatic potential. Specifically, it was suggested that a functional C-I is required for high metastatic features of cancer cells, and the role of C-I could be further examined as a potential target in the development of novel therapies for diagnosing high metastatic cancer types.

Cyclic nucleotide phosphodiesterase inhibitors: possible therapeutic drugs for female fertility regulation.

Cyclic nucleotide phosphodiesterases (PDEs) are group of enzymes responsible for the hydrolysis of cyclic adenosine 3', 5' monophosphate (cAMP) and cyclic guanosine 3', 5' monophosphate (cGMP) levels in wide variety of cell types. These PDEs are detected in encircling granulosa cells or in oocyte with in follicular microenvironment and responsible for the decrease of cAMP and cGMP levels in mammalian oocytes. A transient decrease of cAMP level initiates downstream pathways to cause spontaneous meiotic resumption from diplotene arrest and induces oocyte maturation. The nonspecific PDE inhibitors (caffeine, pentoxifylline, theophylline, IBMX etc.) as well as specific PDE inhibitors (cilostamide, milrinone, org 9935, cilostazol etc.) have been used to elevate cAMP level and inhibit meiotic resumption from diplotene arrest and oocyte maturation, ovulation, fertilization and pregnancy rates both in vivo as well as under in vitro culture conditions. The PDEs inhibitors are used as powerful experimental tools to demonstrate cyclic nucleotide mediated changes in ovarian functions and thereby fertility. Indeed, non-hormonal nature and reversible effects of nonspecific as well as specific PDE inhibitors hold promise for the development of novel therapeutic drugs for female fertility regulation.

Prediction of 3D Protein Structure Based on The Mutation of AKAP3 and PLOD3 Genes in The Case of Non-Obstructive Azoospermia.

BACKGROUND: The present study has been designed with the aim of evaluating A-kinase anchoring proteins 3 (AKAP3) and Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) gene mutations and prediction of 3D protein structure for ligand binding activity in the cases of non-obstructive azoospermic male. MATERIALS AND METHODS: Clinically diagnosed cases of non-obstructive azoospermia (n=111) with age matched controls (n=42) were included in the present case-control study for genetics analysis and confirmation of diagnosis. The sample size was calculated using Epi info software version 6 with 90 power and 95% confidence interval. Genomic DNA was isolated from blood (2.0 ml) and a selected case was used for whole exome sequencing (WES) using Illumina Hiseq for identification of the genes. Bioinformatic tools were used for decode the amino acid sequence from biological database (www.ncbi.nlm.nih.gov/protein). 3D protein structure of AKAP3 and PLOD3 genes was predicted using I-TASSER server and binding energy was calculated by Ramachandran plot. RESULTS: Present study revealed the mutation of AKAP3 gene, showing frameshift mutation at rs67512580 (ACT → -CT) and loss of adenine in homozygous condition, where, leucine changed into serine. Similarly, PLOD3 gene shows missense mutation in heterozygous condition due to loss of guanine in the sequence AGG→A-G and it is responsible for the change in post-translational event of amino acid where arginine change into lysine. 3D structure shows 8 and 4 pockets binding site in AKAP3 and PLOD3 gene encoded proteins with MTX respectively, but only one site bound to the receptor with less binding energy representing efficient model of protein structure. CONCLUSION: These genetic variations are responsible for alteration of translational events of amino acid sequences, leading to protein synthesis change following alteration in the predicted 3D structure and functions during spermiogenesis, which might be a causative "risk" factor for male infertility.

Role of autophagy in regulation of glioma stem cells population during therapeutic stress.

Glioblastoma is highly recurrent and aggressive tumor with poor prognosis where existence of glioma stem cell (GSCs) population is well established. The GSCs display stem cell properties such as self-renewable, proliferation and therapeutic resistance which contribute to its role in tumor progression, metastasis and recurrence. Cancer stem cells (CSCs) can also be induced from non-stem cancer cells in response to radio/chemotherapy that further contribute to cancer relapse post therapy. Role of autophagy has been implicated in the existence of CSCs in different cancers; however, its role in GSCs is still unclear. Moreover, since autophagy is induced in response to various chemotherapeutic agents, it becomes imperative to understand the role of autophagy in therapy-induced pool of CSCs. Here, we investigated the role of autophagy in the maintenance of GSCs and temozolomide (TMZ)-induced therapeutic response. Glioblastoma cell lines (U87MG, LN229) were cultured as monolayer as well as GSC enriched tumorspheres and sub-spheroid population. Our results demonstrated that the tumorspheres maintained higher level of autophagy than the monolayer cells and inhibition of autophagy significantly reduced the percentage of GSCs and their self-renewal capacity. Further, TMZ at clinically relevant concentration resulted in an induction of survival autophagy in glioblastoma cells. We also observed that TMZ treatment significantly increased the expression of GSC markers, suggesting an increased pool of GSCs. Importantly, inhibition of autophagy prevented this TMZ-induced increased GSC population, suggesting a critical role for autophagy in therapy-induced generation of GSC pool. Overall, our findings revealed; i) higher levels of autophagy in GSCs; ii) TMZ induces protective autophagy and up-regulates pool of GSCs; and iii) inhibition of autophagy prevents TMZ-induced GSCs pool suggesting its role regulating GSC population in response to chemotherapy. Our study signifies a positive contribution of autophagy in survival of GSCs which implicates the use of autophagy inhibitors in a combinational approach to target TMZ-induced GSCs for developing effective therapeutic strategies. Further efforts are required to study the role of autophagy in therapy- induced GSC pool in other cancer types for its broad therapeutic implication.

Autophagy in hypoxic ovary.

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.

Necroptosis in stressed ovary.

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.

Necrosis and necroptosis in germ cell depletion from mammalian ovary.

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.