Abstract
In utero and lactational exposures to diethylhexyl-phthalate affect two populations of Leydig cells in male Long-Evans rats
Lin,Han; Lian,Qing-Quan; Hu,Guo-Xin; Jin,Yuan; Zhang,Yunhui; Hardy,Dianne O.; Chen,Guo-Rong; Lu,Zhong-Qiu; Sottas,Chantal M.; Hardy,Matthew P.; Ge,Renshan
Biology of Reproduction 80(5): 882-888
Publication date: 2009
Diethylhexylphthalate (DEHP) has been classified as an anti-androgen.However, whether in utero and lactational exposures of DEHPwill affect Leydig cells has not been well established. In thepresent study, the effects of DEHP exposures on fetal (FLCs)and adult Leydig cells (ALCs) were assessed. Pregnant dams ofLong-Evan rats were treated with 0, 10 and 750 mg/kg body weightof DEHP from Gestational Day 12.5 to Postnatal Day (PND) 21.5.FLC clustering and FLC specific gene expression were examined.Anogenital distances (AGDs) of male pups were assessed at PND2.Serum testosterone (T) levels of male pups and mRNA levels ofALC specific genes were measured at PND21 and 49. AGDs of malepups were significantly shorter in the group treated with 750mg/kg DEHP (mean ± SEM, 3.68 ± 0.16 mm) compared tocontrol (4.62 ± 0.13). FLCs were aggregated after 10 and750 mg/kg DEHP exposures. Several FLC specific genes includingluteinizing hormone receptor (Lhcgr) and steroidogenic enzymegenes were down-regulated at both doses. Serum T levels weresignificantly lower compared to control at PND21 after treatmentof 10 or 750 mg/kg DEHP, and at the higher dose continued tobe lower even up to 49 days postpartum at the higher dose. ThemRNA levels for Lhcgr and steroidogenic enzyme genes were significantlylower at both doses of DEHP at PND21, whereas there were nosignificant differences for these genes at PND49. In conclusion,in utero and continued lactational exposures to DEHP exert long-termdisruption of steroidogenesis of ALCs.
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