Maternal exposure to polybrominated diphenyl ether (BDE-209) during lactation affects germ cell survival with altered testicular glucose homeostasis and oxidative status through down-regulation of Cx43 and p27Kip1 in prepubertal mice offspring

BDE-209, a congener of polybrominated diphenyl ethers (PBDEs), is mainly used as flame retardant and accounts for over 82% of total PBDE usage. PBDEs have recently been detected in human milk and cord blood. BDE-209 possesses weak estrogenic/anti-estrogenic properties and evokes hyperglycemia through impaired glucose homeostasis in rat liver. However, little is known of the effect of lactational exposure to BDE-209 on germ cell survival in relation to testicular glucose homeostasis, estradiol and oxidative status during prepubertal period. The present study, therefore, evaluated the effect of maternal exposure to BDE-209 during lactation on above mentioned parameters with reference to Cx43 and p27Kip1 in prepubertal Parkes (P) mice offspring. Lactating female P mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 0 to PND 28; male pups were euthanized at PND 21 and 28. Maternal exposure to BDE-209 during lactation increased germ cell apoptosis with altered expressions of various cell survival and apoptotic markers along with decreased expression of Cx43 and p27Kip1 in prepubertal mice offspring. Testicular glucose and lactate concentrations were markedly reduced in these pups with down-regulation in GLUT3 and GLUT8 expressions and decreased LDH activity. Rise in oxidative stress in testes with increased estrogen level in these pups was also noted. In conclusion, our results suggest that maternal BDE-209 exposure during lactation affects germ cell survival with altered testicular glucose homeostasis and oxidative status through down-regulation of Cx43 and p27Kip1 in prepubertal mice offspring.