Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration

• Published in: Journal of toxicological sciences Vol. 40; no. 6; pp. 909 - 916
• Main Authors: Kariyazono, Yudai, Taura, Junki, Hattori, Yukiko, Ishii, Yuji, Narimatsu, Shizuo, Fujimura, Masatake, Takeda, Tomoki, Yamada, Hideyuki
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 01.12.2015
• Subjects: Animals; Cadmium Compounds - toxicity; Diethylhexyl Phthalate - toxicity; Endocrine disruptor; Endocrine Disruptors - toxicity; Female; Fetus; Fetus - metabolism; Gonads - physiology; Lead - toxicity; Luteinizing hormone; Luteinizing Hormone - genetics; Luteinizing Hormone - metabolism; Male; Maternal exposure; Maternal Exposure - adverse effects; Maternal-Fetal Exchange; Phosphoproteins - metabolism; Pituitary Gland - physiology; Pregnancy; Rats; Rats, Wistar; RNA, Messenger - metabolism; Steroidogenic acute-regulatory protein; Testis - embryology; Testis - metabolism
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.40.909

The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a ß-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2-ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2’,4,4’-tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHß mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHß. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis.