In utero and lactational exposures to diethylhexyl-phthalate affect two populations of Leydig cells in male Long-Evans rats.
Diethylhexylphthalate (DEHP) has been classified as an antiandrogen. However, whether in utero and lactational exposures of DEHP affect Leydig cells has not been well established. In the present study, the effects of DEHP exposures on fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) were assessed. Pregnant dams of Long-Evans rats were treated with 0, 10, and 750 mg/kg body weight DEHP from Gestational Day 12.5 to Postnatal Day (PND) 21.5. Fetal Leydig cell clustering and FLC-specific gene expression were examined. Anogenital distances (AGDs) of male pups were assessed at PND 2. Serum testosterone levels of male pups and mRNA levels of ALC-specific genes were measured at PNDs 21 and 49. The AGDs of male pups were significantly shorter in the group treated with 750 mg/kg DEHP (mean +/- SEM, 3.68 +/- 0.16 mm) compared with control (4.62 +/- 0.13 mm). The FLCs were aggregated after 10 and 750 mg/kg DEHP exposures. Several FLC-specific genes, including luteinizing hormone receptor (Lhcgr) and steroidogenic enzyme genes, were downregulated at both doses. Serum testosterone levels were significantly lower compared with control at PND 21 after treatment of 10 or 750 mg/kg DEHP, and continued to be lower even up to 49 days postpartum at the higher dose. The mRNA levels for Lhcgr and steroidogenic enzyme genes were significantly lower at both doses of DEHP at PND 21, whereas there were no significant differences for these genes at PND 49. In conclusion, in utero and continued lactational exposures to DEHP exert long-term disruption of steroidogenesis of ALCs.
Lin
Han
H
The Rockefeller University, New York, NY, USA.
Lian
Qing-Quan
QQ
Hu
Guo-Xin
GX
Jin
Yuan
Y
Zhang
Yunhui
Y
Hardy
Dianne O
DO
Chen
Guo-Rong
GR
Lu
Zhong-Qiu
ZQ
Sottas
Chantal M
CM
Hardy
Matthew P
MP
Ge
Ren-Shan
RS
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007774:Lactation; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013739:Testosterone / Q000097:blood
D010968:Plasticizers; D012333:RNA, Messenger; D013739:Testosterone; D004051:Diethylhexyl Phthalate