Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

Abstract

Studies of developmental eff ects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive eff ects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat off spring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg⁄kg body weight (bw)⁄day, GEN 50 mg⁄kg bw⁄day, GEN 400 mg⁄kg bw⁄day, and two combinations of the two compounds (DEHP 250 mg⁄kg bw⁄day + GEN 50 mg⁄kg bw⁄day, DEHP 250 mg⁄kg bw⁄day + GEN 400 mg⁄kg bw⁄day). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coeffi cient, AGD / body weight 1 / 3 , serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bw⁄day), GEN(50mg/kg bw⁄day) or GEN(400mg/kg bw⁄day) alone were not signifi cantly diff erent from the control group. When exposed to (DEHP 250mg/kg bw⁄day +GEN 50mg/kg bw⁄day) together during pregnancy and lactation, serum testosterone concentration, epididymis coeffi cient and Cypal17a1,Scarb1 m RNA expression signifi cantly decreased compared to the control and GEN(50mg/kg bw⁄day). When exposed to (DEHP 250mg/kg bw⁄day +GEN 400mg/kg bw⁄day) together during pregnancy and lactation, AGD / body weight 1 / 3 , serum testosterone concentration, testis and epididymis coeffi cient and Star, Cypal17a1 mRNA expression appeared signifi cantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most signifi cant alterations in the neonate, especially with GEN at high dose, although the eff ect of the DEHP-GEN mixture on adult off spring should be observed further.

Prepubertal Exposure to Genistein Alleviates Di-(2-ethylhexyl) Phthalate Induced Testicular Oxidative Stress in Adult Rats

“…Recent studies revealed that exposure to EDCs causes imbalance in prooxidant/antioxidant levels and thereby promotes the generation of ROS [31, 32]. DEHP has been proven to have deleterious effects on the male reproductive system via inducing dramatic changes in germ cells, Sertoli cells, and Leydig cells [33, 34]. However, the underlying mechanisms by which DEHP exerts toxic effects on reproductive system has not yet been fully elucidated.…”

Prenatal Exposure to DEHP Affects Spermatogenesis and Sperm DNA Methylation in a Strain-Dependent Manner

“…The mRNA expressions between controls and DEHP 300 conditions in both backgrounds (C57BL/6J and FVB/N) were measured by RT-qPCR for a subset of six selected genes; 1) Star , 2) Piwil2 , 3) Piwil4 , 4) Rabl2 , 5) Pacrg and 6) Ifg2r . First, Star was selected because of its central role in steroid hormone synthesis and its reported expression modified after DEHP exposure in various organisms [ 42 – 50 ]. Star revealed opposite methylation and expression changes upon DEHP exposure in the organism Oryzias melastigma [ 51 ].…”

Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring

“…Exposure to DEHP is associated with precocious puberty in girls and risk of breast cancer (Yen et al 2011). Experimental evidence indicates that lactational exposure to DEHP impairs the development and physiological function of gonads and the endocrine, nervous and cardiovascular systems in rats (Andrade et al 2006;Carbone et al 2012;Zhang et al 2013;Mangala Priya et al 2014).…”