title: Neonatal exposure to benzo[a]pyrene decreases the levels of serum testosterone and histone H3K14 acetylation of the StAR promoter in the testes of SD rats.
abstract: Although benzo[a]pyrene (BaP) is an environmental endocrine disrupter, it has been unclear whether neonatal exposure to BaP affects the testosterone level and, if so, whether this influence persists into adulthood. In this present study, we gave neonatal rats (through oral gavages) doses of 0, 5, 10, or 25mg/kg day of BaP in corn oil from postnatal day 1 (PND 1) to PND 7. The rats were sacrificed at PND 8, PND 35, and PND 90. BaP exposure was confirmed through the induction of liver and testis CYP1A1 mRNA expression at PND 8 (i.e., immediately after exposure). The testicular daily sperm production and the sperm counts of the epididymis cauda at PND 90 were significantly lower than those of the control. The serum testosterone levels decreased markedly at PND 8, PND 35, and PND 90 after neonatal BaP exposure relative to those of the control. The mRNA expressions of StAR also decreased relative to those of the control at PND 8, PND 35, and PND 90, although the mRNA expressions of P450c17 and 17β-HSD were suppressed significantly only at PND 8. To further elucidate the mechanism of the persistent decrease in the mRNA expression of StAR, we determined the histone acetylation level in the StAR promoter. The extent of acetylation of H3K14 in the determined region decreased after neonatal exposure to BaP; this phenomenon persisted to the adult stage. Our results indicate that neonatal exposure to BaP damages testosterone production and sperm counts in the long term, possibly as a result of epigenetic regulation in the StAR promoter region.
authors.affiliation: School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032, China.
authors.forename: Jiren
authors.initials: J
authors.lastname: Liang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Cuizhen
authors.initials: C
authors.lastname: Li
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ding
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006657:Histones; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D001564:Benzo(a)pyrene; D013739:Testosterone; D019363:Cytochrome P-450 CYP1A1; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme