Ameliorating Effects of Natural Antioxidant Compounds on Female Infertility: a Review.

The prevalence of female infertility cases has been increasing at a frightening rate, affecting approximately 48 million women across the world. However, oxidative stress has been recognized as one of the main mediators of female infertility by causing various reproductive pathologies in females such as endometriosis, PCOS, preeclampsia, spontaneous abortion, and unexplained infertility. Nowadays, concerned women prefer dietary supplements with antioxidant properties over synthetic drugs as a natural way to lessen the oxidative stress and enhance their fertility. Therefore, the current review is an attempt to explore the efficacy of various natural antioxidant compounds including vitamins, carotenoids, and plant polyphenols and also of some medicinal plants in improving the fertility status of females. Our summarization of recent findings in the current article would pave the way toward the development of new possible antioxidant therapy to treat infertility in females. Natural antioxidant compounds found in fruits, vegetables, and other dietary sources, alone or in combination with other antioxidants, were found to be effective in ameliorating the oxidative stress-mediated infertility problems in both natural and assisted reproductive settings. Numerous medicinal plants showed promising results in averting the various reproductive disorders associated with female infertility, suggesting a plant-based herbal medicine to treat infertility. Although optimum levels of natural antioxidants have shown favorable results, however, their excessive intake may have adverse health impacts. Therefore, larger well-designed, dose-response studies in humans are further warranted to incorporate natural antioxidant compounds into the clinical management of female infertility.

Cadmium as a testicular toxicant: A Review.

Cadmium (Cd) is a toxic heavy metal with no known biological functions in the human body. Due to a considerably long biological half-life and very low rate of excretion, accumulation of Cd in different body organs (eg, liver, kidney, and testes) over time is associated with perturbed functioning of these organs. Recent studies have shown the extreme sensitivity of the testes to Cd toxicity. In testes, Cd has been reported to induce oxidative stress, apoptosis of spermatogenic cells, reduction in androgen production and sperm functions. Moreover, Cd in combination with other environmental toxicants may be responsible for the declining fertility of males in both animals and humans. Pinpointing how Cd toxicity affects various testicular processes will be imperative for the development of preventative measures to promote fertility among males. Therefore, in the present review, we summarize the recent findings related to the Cd-induced oxidative toxicity, apoptotic toxicity, steroidogenic toxicity, and spermatotoxicity, along with their possible mechanisms in testicular tissue of different animal species. In addition, the utilization of various antioxidant compounds, medicinal plants and other compounds for the management of Cd toxicity in testes is discussed.

N-acetyl-l-cysteine mediated regulation of DNA fragmentation, an apoptotic event, against methoxychlor toxicity in the granulosa cells of ovarian antral follicles.

Methoxychlor (MXC), an organo-chlorine insecticide, is a reproductive toxicant in females, causing apoptosis-mediated follicular atresia. To elucidate the potentials of Methoxychlor as a geno-toxicant, granulosa cells of healthy antral follicles, exposed to MXC and antioxidant, N-acetyl-l-cysteine, were studied by the terminal deoxynucleotidyltransferase-dUTP nick end-labelling and single-cell gel electrophoresis (comet) assays. MXC caused DNA fragmentation, as revealed by the increased incidence of dark brown condensed TUNEL positive cells in contrast with lightly brown TUNEL negative cells with maximum TUNEL positive cells were observed in 100 µg/mL MXC treated groups. Quantitatively, maximum geno-toxicity was exhibited at highest MXC treatment with percent tail DNA as 17.87 ± 0.85, 41.16 ± 3.94, and 47.73 ± 3.71 in comparison with control (0.65 ± 0.03, 2.91 ± 0.27, and 7.16 ± 1.39) after 24, 48 and 72 h exposure duration, respectively. MXC treated groups exhibited Type 1-Type 3 comets as compared to Type 0 comets in control groups. Supplementation of NAC led to significant (p < 0.05) decline in geno-toxicity in MXC treated groups with maximum amelioration observed at 5 and 10 mM. Consequently, increased DNA damage attributed to the granulosa cells apoptosis in response to Methoxychlor exposure was significantly combated by NAC supplementation, preventing the geno-toxicity induced cyto-toxicity in GCs.

Aggregation, adhesion and efficacy studies of probiotic candidate Pediococcus acidilactici NCDC 252: a strain of dairy origin.

Aggregation and adhesion capability and survival efficacy of candidate probiotic strain Pediococcus acidilactici NCDC 252 under simulated gastric, intestinal and vaginal conditions was studied. The strain exhibited strong autoaggregation phenotype and coaggregation with other Lactic acid bacteria (LAB) and E. coli. The adhesion studies of NCDC 252 to pig's intestinal epithelial cells showed its adhesive ability. Aggregation and adhesiveness were related through cell surface proteins as removal/extraction of surface proteins resulted in altered aggregation and no adhesiveness. Cell surface proteins were analysed by SDS-PAGE and also in silico analysed from its genome. SDS-PAGE analysis of cell surface proteins of NCDC 252 revealed two potential proteins of approximately 74.3 and 53.6 kDa to be involved in host-probiotic interaction. Removal of cell surface proteins by LiCl-treatment (5 mol l-1) resulted in loss of aggregation and adhesiveness. Further survival of NCDC 252 under simulated gastrointestinal and vaginal conditions in terms of high viable counts confirmed its efficacy for its survival under gut and urogenital conditions. These observations suggest that it can be used further in functional foods, nutraceuticals and in combating urogenital infections. As NCDC 252 was able to survive in intestinal conditions, interaction of its cell surface proteins with intestinal mucins was studied in silico by docking. Highest affinity of adhesion was observed for MUC3B. In conclucion, NCDC 252, exhibited aggregation phenotype and adhesion capability. Survivability of NCDC 252 under simulated conditions and its interaction with human mucins confirms its efficacy to be used as probiotic.

Effective attenuation of glyphosate-induced oxidative stress and granulosa cell apoptosis by vitamins C and E in caprines.

Pesticides are known to cause a wide range of reproductive problems that possess degenerative effects on mammalian fertility. Glyphosate (GLP), a broad-spectrum organophosphate herbicide, is known to be a potent mammalian toxicant. The present study aims at assessing the GLP-induced (0.1, 2.0, and 4.0 mg/ml) granulosa cells toxicity and evaluating the mitigating effects of vitamins C and E (0.5 mM and 1.0 mM) in healthy caprine antral follicles, cultured in vitro in a dose- and time-dependent manner (24, 48, and 72 hr) and subjected to various cytotoxic and geno-toxic analysis, namely, classic histology, EB/AO differential staining, oxidative stress parameters, and antioxidant enzymatic activity. The histomorphological analysis and EB/AO staining elucidated increase in the incidence of apoptotic attributes within granulosa cells with increasing dose and duration of the GLP treatment. The highest apoptotic frequency was observed at 4.0 mg/ml GLP after 72-hr exposure duration in comparison with the control. GLP exposure also led to a significant decline in the antioxidant enzymes' activity, namely, SOD, catalase, and GST along with enhanced lipid peroxidation and reduced FRAP activity in a dose- and time-dependent manner. Vitamins C and E supplementation decreased oxidative stress-mediated granulosa cells apoptosis, suggesting its efficiency to diminish GLP-mediated GCs cytotoxicity and thereby, preventing associated fertility disorders.

Antiapoptotic effects of vitamins C and E against cypermethrin-induced oxidative stress and spermatogonial germ cell apoptosis.

Toxicological studies have demonstrated the relation between use of agrochemicals and fertility issues within males. Thus, the present study aimed to elucidate the propensity of cypermethrin (CYP) in bringing testicular germ cell apoptosis and effective attenuation by vitamins C and E in caprines. Reproductive toxicity of CYP was evaluated using histomorphological, cytological, and biochemical changes in the testicular germ cells in dose-dependent (1, 5, 10 µg/mL) and time-dependent (4, 6, 8 h) manner. Histological and ethidium bromide/acridine orange fluorescence staining exhibited that vitamins C and E (0.5 and 1.0 mM) successfully diminished the CYP-induced testicular germ cells apoptosis. CYP exposure along with vitamins C and E supplementation also resulted in significantly increased ferric reducing antioxidant power activity along with the antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione-s-transferase, and decreased lipid peroxidation in testicular germ cells. Thus, vitamins C and E ameliorated CYP-induced testicular germ cell apoptosis, thereby preventing spermatogonial cells degeneration and male infertility.

N-Acetyl-cysteine mediated inhibition of spermatogonial cells apoptosis against malathion exposure in testicular tissue.

Toxicological studies so far suggest that excessive use of malathion, an organophosphate insecticide, causes serious ill-effects in mammalian reproductive physiology. The present study aims at assessing malathion-induced toxicity in a dose- and time-dependent manner with mitigating effects of N-acetyl-l-cysteine. The testicular germ cell viability was monitored using MTT assay, where NAC, being an antioxidant significantly reduced malathion-induced toxicity by enhancing the frequency of cell viability. The histomorphological analysis showed that NAC successfully diminished several apoptotic features in testicular cells, induced by malathion. The differential EB/AO staining revealed a significant decline in the percentage of apoptosis after NAC supplementation. NAC also diminished the malathion-induced DNA fragmentation along with significantly reduction in oxidative stress parameters causing decrease in lipid peroxidation and enhancement of ferric reducing antioxidant power within testicular germ cells. Thus, NAC mitigated the malathion-induced toxicity, proving its potential in infertility treatment.

N-acetyl cysteine-mediated effective attenuation of methoxychlor-induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary.

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 (rCAT = -0.67, rSOD = -0.56, rGST = -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.