Influence Of Perinatal Exposure To Environmental Estrogen On Testicular Development And Spermatogenesis In The Rat Offspring And Its Molecular Mechanism

Bisphenol A (bisphenol A, BPA), is a kind of phenolic environmentalestrogens, whose structure is similar to estradiol (E2) and DES (diethylstilbestrol,DES).Bisphenol A (bisphenol A, BPA) is mainly used for the production ofpolycarbonate, epoxy resins, polysulfone resins, polyphenylene ether resin and otherpolymer materials which can also be used in the production of plasticizers, flameretardants, antioxidants, heat stabilizers, anti-aging agent of rubber, pesticides, paintsand other fine chemical products. Repeated use of these items and are exposed tointense heat can cause the BPA leaching. BPA is not only has been widely detected ina variety of environmental media and lower organisms, but also in the populationsample of many countries, such as blood, urine, semen, amniotic fluid, milk medium,there have been reported to be detected[1].This suggests that bisphenol A can passthrough the placental barrier to affect the development of the offspring.The purpose of this study is to investigate the perinatal low-dose BPA exposureon the reproductive system of male offspring and its mechanism.2ug/kg BW/d ofBPA was injected subcutaneously from tenth day of the SD rats during pregnancy tothe postpartum seventh day (GD10-PND7). We then observed the development of F1male rats after birth:â‘ Serum follicle stimulating hormone (FSH), luteinizinghormone (LH), serum testosterone (T), serum estradiol (E2) and Intratesticulartestosterone levels(PND18,PND21,PND24);â‘¡Body weight, testis weight(PND11,PND18, PND21, PND24);â‘¢The testicular morphology changes;â‘£The PND54(thetime for the first wave sperm appearing in epididymal tail)epididymal tail sperm count and morphology changes.The results showed:â‘ the BPA group male F1rat serum follicle stimulatehormone (FSH) and luteal generate hormone (LH) level was higher than the controlgroup while Intratesticular testosterone level was lower than the control group fromthe PND21;â‘¡the BPA group male F1rat weight was high than control group fromthe PND21;â‘¢the BPA group male F1rat was higher than the control group in thepercentage of sperm cells positive seminiferous tubules number of the totalseminiferous tubule number, the average number of sperm cells in each seminiferoustubule, the average diameter of seminiferous tubule on the PND24(the time for SDmale rat spermatogenic luminal sperm cells);â‘£the BPA group male F1rat issignificantly higher in the first wave of sperm deformity rate in the PND54.In order to explore the mechanism of testicular testosterone levels decline in theBPA group male F1rat, we used real-time PCR to detect the male F1rat ofintratesticular testosterone synthesis rate-limiting enzyme gene star, p450scc,CYP17a,3-HSD,17-HSD relative mRNA levels. Our results show that among ofmost of them there was a downward trend in BPA group relative to the control group,and that3-HSD relative mRNA was significantly decline in the PND21BPA group.In order to explore the mechanism of spermatogenic cells meiotic cell cycleabnormalities in the BPA group male F1rat, we used real-time PCR to detect themale F1rat meiosis cell cycle proteins and their kinase genes and the checkpointgenes relative mRNA levels. CyclinA1relative mRNA expression levels increasedsignificantly in the BPA group male F1rat relative to the control group on thePND21and PND24; the checkpoint gene TRIP13relative mRNA expression levelsdecreased in the BPA group male F1rat relative to the control group on the PND21.These genes were essential for meiosis, so we speculate that the differences in theirmRNA levels may have some connection with testicular and sperm morphology difference. We found spermatogenesis-related proto-oncogene c-jun and c-fosrelative mRNA expression levels were different between the BPA group male F1ratand the control group combining the morphological phenotype and the expression ofthese genes trends.Therefore, we hypothesized that perinatal SD rats low dose BPA exposure canaffect F1male rat spermatogenic cells meiosis-related events, which contributing tospermatogenesis disorder and the first wave of sperm abnormality rate increasing ofepididymal tail.This provides a basic for further studying molecule mechanisms ofthe EDCs leading to male infertility.