Effect of Plasticizers on Testis with Special Reference to Sertoli Cell Functions pp. 89-112
Authors: (Oli Sarkar, P. P. Mathur, Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India)
Abstract: Over the past five decades there have been reports of progressive decline in male reproductive health, which has been correlated with increase in the amount of chemical pollutants in the environment. Plastics are one of the major environmental pollutants today and have become an integral part of urban lifestyle. Polyvinyl chlorides (PVC) and polycarbonates (PC) make up most of household plasticware. During manufacture of PVC and PC, polymers are treated with phenolic additives called ―plasticizers‖ that enhance their flexibility and toughness. Some of these phenolic compounds have estrogenic and anti-androgenic properties and are known to harm the male reproductive system in a time- (fetal, neonatal and adult), duration- and dose-dependent manner. The male reproductive system is responsible for the production of spermatozoa and enabling the male to be fertile. Testis is the site of spermatogenesis and is constituted by seminiferous tubules populated by Sertoli and germ cells. Sertoli cells are nurse cells that nourish developing germ cells to sustain spermatogenesis, which due to their non-regenerative nature are vulnerable to toxicants. In this review we discuss the effects of two commonly used plasticizer groups on Sertoli cell functions. The phthalate group of PVC additives that includes Bis- (2-ethylhexyl) phthalate (DEHP), its active metabolite Mono- (2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) has been shown to disrupt Sertoli cell cytoskeleton causing vacuolization. The inability of immature Sertoli cells to anchor germ cells resulted in an efflux of germ cells leaving behind Sertoli cell-only (SCO) tubules. DEHP has been shown to cause a decrease in testosterone synthesis resulting in delayed Sertoli cell maturation and to induce apoptosis of germ cells. The phenolic group of plasticizers that includes 4-(3‘, 6‘ dimethyl 3-heptylphenol) (Nonylphenol) and 4, 4'-dihydroxy-2, 2-diphenylpropane (Bisphenol A or BPA) has been shown to cause disassembly of Sertoli cell junctions by disrupting actin-binding proteins. Both Bisphenol A and Nonylphenol have been shown to hamper the activities of anti-oxidant enzymes and increase the levels of reactive oxygen species (ROS) leading to conditions of oxidative stress and induction of Fas/ FasL-mediated Sertoli cell apoptosis. Bisphenol A has been shown to cause sperm acrosomal abnormalities and inhibit spermatogenesis. Recent studies show that the use of plasticizers must be vigilantly monitored to avoid any adverse effects to male reproductive health.