Abstract

MITIGATION OF OXIDATIVE STRESS–INDUCED CELLULAR DAMAGE BY SELECTED COMPOUNDS IN AN IN VITRO MODEL OF MALE INFERTILITY

Maignanamoorthy V., Asmitha R. V., Monica T., Rajesh V., *Anandhi B.

Abstract

Male infertility is now viewed as a disorder of cellular stress where too much reactive oxygen species (ROS) has a detrimental effect on sperm function, spermatogenesis and somatic cells of the testicle. Physiological ROS are necessary for capacitation and acrosome reaction and excess are pro-oxidants that can induce lipid peroxidation, depolarize mitochondrial membranes, cause protein oxidation, fragmentation of DNA and apoptosis. This review aims at summarizing the mechanistic as well as experimental studies of the oxidative stress induced cellular damage and the protective role of certain naturally occurring and synthetic compounds in in vitro models related to male infertility. The attached topic draft was developed through a structured approach of literature screening in PubMed/MEDLINE, Scopus, Web of Science and in journals cross indexed in the above databases. Special focus is paid to TM3 Leydig cells, TM4 Sertoli cells, GC-1 spermatogonial cells, isolated spermatozoa, and oxidative induction models (hydrogen peroxide, tert-butyl hydroperoxide, heavy metals, endocrine disruptors and inflammatory mediators). The literature reviewed suggests that antioxidant compounds exert a protective effect on reproductive cells by scavenging ROS, increasing glutathione levels and levels of antioxidant enzymes, activating Nrf2/Keap1 pathway, inhibiting NF-kappaB/MAPK injury pathways, stabilizing mitochondria and correcting Bax/Bcl-2/caspase apoptosis pathway. The possible sources of flavonoids, phenolics and alkaloids for in vitro and in silico validation in the future are discussed as Boerhavia erecta and related phytochemical rich preparations. The paper concludes that the combined use of the following experimental designs: viability assays, estimation of ROS and MDA, mitochondrial membrane potential measurement, DNA fragmentation assays, Western blotting/qPCR, docking and network pharmacology will lead to a more robust translation of cell models to male infertility drugs.

Keywords: Oxidative stress;(ROS); Sperm DNA fragmentation; TM3 cells; TM4 cells; GC-1 cells; Boerhavia erecta; Molecular docking; Network pharmacology; In vitro models.