Showing papers by "Chandana Haldar published in 2021"

Melatonin ameliorates Bisphenol S induced testicular damages by modulating Nrf-2/HO-1 and SIRT-1/FOXO-1 expressions.

Abstract: BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF-kB/COX-2) and apoptosis (caspase-3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative load as evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1, SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl-2), gap junction (connexin-43) and decreased apoptosis (caspase-3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus.

Melatonin Ameliorates LPS-Induced Testicular Nitro-oxidative Stress (iNOS/TNFα) and Inflammation (NF-kB/COX-2) via Modulation of SIRT-1

Abstract: Lipopolysaccharide (LPS) - an endotoxin that is being extensively used in laboratory to mimic microbial infection that adversely affects male fertility. This study investigated the protective effects of melatonin on LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages in the testes of male golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin and LPS for 7 days. Testes of LPS treated hamsters showed degenerative changes (appearance of vacuoles, exfoliation, and depletion of germ cells in the seminiferous tubules), adverse effects on spermatogenesis (sperm count and viability), and steroidogenesis (declined serum and testicular testosterone). Furthermore, LPS treatment decreased melatonin content, melatonin receptor (MT1), and antioxidant potential (catalase and SOD), and simultaneously increased nitro-oxidative stress (CRP, nitrate, TNFα). LPS upregulated NF-kB, COX-2, and iNOS expressions to increase testicular inflammatory load that resulted in the decrease of germ cell proliferation and survival, thus culminating into germ cell apoptosis as indicated by AO-EB staining and caspase-3 expression. Administration of melatonin with LPS showed improved testicular histoarchitecture, sperm parameters, and testosterone level. Melatonin increased testicular antioxidant status (SOD, catalase) to counteract the LPS-induced testicular ROS and thus reduced testicular nitro-oxidative stress. Furthermore, melatonin treatment upregulated testicular SIRT-1 expression to inhibit LPS-induced inflammatory proteins, i.e., NF-kB/COX-2/iNOS expression. The rescue effect of melatonin was further supported by increased germ cell survival (Bcl-2), proliferation (PCNA), and declined apoptosis (caspase-3). In conclusion, our result demonstrated that melatonin rescued testes from LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages by upregulation of SIRT-1.

Management of ovarian functions by melatonin

Abstract: Extensive research has unraveled a niche for melatonin that is of great significance for the female reproductive physiology. The potency of melatonin as an antioxidant, anti-inflammatory, and anti-apoptotic agent is being utilized to benefit female reproductive anomalies. Melatonin receptors have been localized in the Supra Chaismatic Nucleus (SCN), pars tuberalis (PT), and the gonads suggesting the regulation of reproduction by melatonin not only at a higher level but also on the gonads through complex interrelated mechanisms. Melatonin secreted by the pineal gland acts on the hypothalamus to regulate gonadotropin-releasing hormone and subsequently gonadotropin (FSH/LH) release from the PT. However, the de novo synthesis of this indoleamine reported in the gonads gave rise to the idea of a more localized action. The mammalian ovary has all the molecular machinery required for the biosynthesis of melatonin and interestingly concentration of melatonin in the follicular fluid of pre-ovulatory follicles is much higher than circulatory melatonin even in humans. This locally produced melatonin has been shown to modulate various pathways governing ovarian steroidogenesis. Further, melatonin and its receptors play a significant role in antioxidant defense mechanism of ovary for follicular growth and maturation. Exposure to stress strongly influences hypothalamic-pituitary-adrenal axis and elevated glucocorticoid levels suppress various ovarian functions including implantation thereby pregnancy. Melatonin acts antagonistically with glucocorticoids, making it crucial for the management of the female reproductive functions/dysfunctions. Usage of melatonin during in vitro fertilization (IVF) procedures has been found to improve oocyte quality, survival, and fecundity. Therefore, in future, melatonin can be implicated as preferable therapeutic especially in IVF and assisted reproductive techniques.

Chronodisruption and Loss of Female Reproductive Potential Due to Shift Work

Abstract: Entrainment of 24 hrs light/dark cycle is nowadays getting altered in corporate sector and even at home due to over exposure to artificial light at night (ALAN) and is commonly denoted as chronodisruption. Chronodisruption interferes with the daily physiology that is regulated by SCN/pineal-melatonin/Hypothalamo-Pituitary axis. In females, reduction in sleep due to shift work desynchronizes HPG-HPA axis induces a stress like condition, accompanied by increased free radical generation in ovary leading to polycystic ovaries, depletion of ovarian reserve, luteal phase defects, endometriosis, implantation failure, etc. Evidence suggest that there is remedial rescue by management of circulatory melatonin due to its chronobiotic/antioxidant/anti-inflamatory/antiapoptotic potentials and its role in ovarian folliculogenesis and steroidogenesis. Advancement in melatonin research suggests that it could be beneficial for commercial use, that is, (1) as an endogenous synchronizer, (2) to improve the quality of oocyte, and (3) for promoting success in the frequency of IVF.

Impact of coronavirus disease-2019 pandemic on assisted reproductive technologies: Potentialities of melatonin in management

Abstract: The world is still grappling with the threat due to the emergence of the coronavirus disease-2019 (COVID-19) caused by a new variant of coronavirus. The high transmission of the virus among humans has led to a pandemic and there is also emergence of mutant strain of virus (severe acute respiratory syndrome coronaviruses 2 Variant VOC 202012/01) within communities. With the uncertainties in the development, efficacy and reach of an effective vaccine among the masses, it has become a mammoth task for human beings to carry on with the dayto-day task and lifestyle. This has severely impacted the health-care services including the fertility treatments. The assisted reproductive technology (ART) services have accordingly molded itself to cater to patients. There are various guidelines and regulations introduced to provide fertility services on the basis of priority of the patients seeking treatments, keeping in compliance to the safety measures for the healthcare staffs and patients. On the other hand, couples wish to pursue their way to parenthood even in the testing times. Melatonin, a neurohormone, is a multipotent molecule associated with male and female reproduction and is being protectively involved in the various reproductive processes. It maintains the circadian rhythmicity of various hormones and has potentials in treating COVID-19 patients. Its use in IVF procedures can be protective and effective measure to deal with the uncertainties of time. Its immune enhancing role can be utilized in fulfilling the patients’ health and achieving fertility goals contributing to the success of ART.