Impairment in protein expression profile of testicular steroid receptor coregulators in male rat offspring perinatally exposed to Bisphenol A.
OBJECTIVE
Steroid hormones and steroid receptors (SRs) play a crucial role in spermatogenesis. Steroid receptor coregulators are the major determinants of SR functioning, and any alteration in their expression is known to be associated with impaired spermatogenesis. Since Bisphenol A (BPA) exposure leads to an impairment of spermatogenesis, we hypothesized that this effect could be associated with the altered expression of steroid receptors and their coregulators in the testes. The present study describes the effect of perinatal exposure of rats to BPA on the expression profile of testicular steroid receptor coregulators in the F(1) generation. These effects were further studied in the F(2) and F(3) generations to determine vertical transmission.


METHODS
Pregnant female rats (F(0)) were gavaged daily with BPA (1.2 and 2.4 microg/kg bw) (or vehicles for controls) from gestation day 12 through postnatal day (PND) 21 to obtain the F(1) and subsequent F(2) and F(3) generations. Immunohistochemical localization of steroid receptor coactivator-1 (SRC-1), G-receptor integrating protein-1 (GRIP-1), p300/CBP/cointegrator-associated protein (p/CIP) and nuclear corepressor (NCoR) was carried out in the testes of F(1), F(2) and F(3) generation adult rats.


RESULTS
A significant reduction in the expression of SRC-1 and NCoR, with a parallel increase in the expression of p/CIP and GRIP-1, was observed in the testes of rats exposed perinatally to BPA. Surprisingly, a similar pattern was observed in the testes of F(2) and F(3) rats.


CONCLUSIONS
Perinatal exposure of male rats to BPA leads to transgenerational perturbations in the expression profile of testicular steroid receptor coregulators.
Salian
Smita
S
National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, Maharashtra, India.
Doshi
Tanvi
T
Vanage
Geeta
G
D000818:Animals; D001559:Benzhydryl Compounds; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D051548:Histone Acetyltransferases / Q000096:biosynthesis / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D056920:Nuclear Receptor Coactivator 1; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000096:biosynthesis*; D012671:Seminiferous Tubules / Q000187:drug effects / Q000254:growth & development; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D052244:Endocrine Disruptors; D051548:Histone Acetyltransferases; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D056920:Nuclear Receptor Coactivator 1; D010636:Phenols; D011987:Receptors, Steroid; D014157:Transcription Factors; C491308:Grip1 protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds