Methoxychlor (MXC), an organochloride insecticide, is a potent toxicant-targeting female reproductive system and known to cause follicular atresia by inducing apoptosis within granulosa cells. Oxidative stress plays a pivotal role in apoptosis; thus, this study focuses on the ameliorative action of N-acetyl cysteine (NAC) on MXC-induced oxidative stress and apoptosis within granulosa cell of caprine ovary. Classic histology, fluorescence assay, and biochemical parameters were employed to evaluate the effect of varied concentration of NAC (1, 5, and 10 mM) on granulosa cell apoptosis after 24, 48, and 72 h exposure duration. Histomorphological studies revealed that NAC diminished the incidence of apoptotic attributes like condensed or marginated chromatin, pyknosis, crescent-shaped nucleus, empty cell spaces, and degenerated cellular structure along with the presence of cytoplasmic processes within granulosa cells in dose- and time-dependent manner. NAC significantly downregulated the percentage of MXC-induced granulosa cell apoptosis within healthy ovarian follicle with its increasing dose, maximum at 10 mM concentration. It also significantly (p < 0.05) upregulated the activity of antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione-s-transferase, along with ferric reducing antioxidant power further declining lipid peroxidation in the MXC-treated caprine ovary. The results revealed a negative correlation between apoptosis frequency and antioxidant enzymes' activity (r = -0.67, r = -0.56, r = -0.31; p < 0.05) while a positive correlation was observed with lipid peroxidation (r = 0.63; p < 0.05) after NAC supplementation. Thus, NAC supplementation reduces the MXC-generated oxidative stress that perhaps declines the ROS generating signal transduction pathway of apoptosis, thereby preventing MXC-induced granulosa cell apoptosis and follicular atresia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 156-166, 2017.

Toxicological studies have demonstrated the exposure-risk relationship of several pesticides on reproduction of living organisms. To evaluate the role of malathion as a reproductive toxicant, this study aims at assessing the cytological and biochemical changes in the granulosa cells after malathion exposure in dose (1 nM, 10 nM, 100 nM) and time (4 h, 6 h, 8 h) dependent manner. Histomorphological analysis, fluorescence assay, apoptosis quantification, and terminal deoxynucleotidyl transferase d-UTP mediated nick end labeling (TUNEL) assay were done to determine cytological changes, whereas antioxidant enzyme assays were done to measure the oxidative stress in malathion treated ovarian antral follicles. Histological studies exhibited the occurrence of highly condensed or marginated chromatin with fragmented nucleus, pyknosis, loss of membrane integrity, increased empty spaces, and vacuolization in malathion treated granulosa cells. Ethidium bromide/acridine orange (EB/AO) fluorescence staining demonstrated a significant increase in incidence and percentage of apoptosis after malathion exposure (p < 0.001), both between and within the groups. Malathion exposure also resulted in increased DNA fragmentation and decline in both antioxidant enzymes activity namely catalase (CAT) and superoxide dismutase (SOD) in granulosa cells of antral follicles. Moreover, there was found a significant negative correlation between the apoptosis incidence and the level of antioxidant enzymes activity, SOD (r = -0.73 p < 0.01) and CAT (r = -0.80 p < 0.01), in malathion treated ovarian antral follicles. Thus, highlighting the role of DNA fragmentation and declining antioxidant level as a possible mechanism underlying malathion induced reproductive toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1944-1954, 2016.

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The reproductive performance of most of the species is adversely affected by hazardous heavy metals like lead, cadmium, mercury, arsenic, zinc, and copper. Heavy metals are liberated in the environment by natural sources like rock weathering, volcanic eruption, and other human activities like industrial discharge, mineral mining, automobile exhaust, and so forth. Heavy metals alter several reproductive functions in both males and females like a decrease in sperm count, motility, viability, spermatogenesis, hormonal imbalance, follicular atresia, and delay in oocyte maturation, and so forth, and thus, forms an important aspect of reproductive toxicology. The present review compiles toxicity aspects of various heavy metals and their efficacy and mechanism of action in mammals.

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