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

Abstract

-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 (CH 3 HgOH). 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 CH 3 HgOH 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.

Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview

“…DEHP decreases the expression of steroidogenic acute regulatory protein (StAR) mRNA in pregnant mice, which reduces steroidogenesis catastrophically in both mice and humans. DEHP also lowers the in utero fetal testicular mRNA levels of 17 α -hydroxylase and cytochrome P450 17A1, which are key enzymes in the steroidogenic pathway [ 17 ]. The above two conditions can occur from either direct exposure of fetal testis or indirect maternal exposure.…”

Di-(2-ethylhexyl) Phthalate (DEHP) and Uterine Histological Characteristics

“…It reduces sperm quality, causes testicular atrophy, and induce Sertoli cell vacuolation and hypospermatogenesis (Hauser, 2006;Street et al, 2018). DEHP downregulates steroidogenic acute regulation protein (StAR) and in utero fetal testicular 17α-hydroxylase and cytochrome P450 17A1 mRNAs by direct action on the testis (Kariyazono et al, 2015). Male rats exposed via placental diffusion to DEHP at a dosage range of 100-750 mg/kg BW/d present with diminished mineralocorticoid receptor expression in the Leydig cells and reduced testosterone levels (Martinez-Arguelles et al, 2009.…”

Organotin Exposure and Vertebrate Reproduction: A Review

“…Intrauterine exposure to TBTCl at different doses and routes did not alter the male:female ratio of pups in rats ( 50 , 53 ). However, the exposure of zebra fish to 1 µg of TBTCl/g via the diet increased the proportion of females ( 19 ).…”

“…Rats exposed to TBTCl showed a dose-dependent increase in serum testosterone and LH levels as well as a reduction in the serum estrogen levels only in animals exposed to 125 ppm of TBTCl ( 12 ). In addition, mice exposed to a TBTCl dose of 10 mg Sn/kg in GD15 showed increased expression of the LH β-subunit mRNA ( 53 ). Meanwhile, mice exposed to TBTCl from the GP until weaning showed a reduction in intratesticular estrogen levels only on PND 49 ( 54 ).…”