Role of the 17β-hydroxysteroid dehydrogenase signalling pathway in di-(2-ethylhexyl) phthalate-induced ovarian dysfunction: An in vivo study

Sci Total Environ. 2020 Apr 10:712:134406. doi: 10.1016/j.scitotenv.2019.134406. Epub 2019 Dec 10.

Abstract

Plasticiser di-(2-ethylhexyl) phthalate (DEHP) is associated with female reproductive endocrine toxicity. Our previous study found that mono-(2-ethylhexyl) phthalate (MEHP), the metabolite of DEHP, can interfere with ovarian function via dysregulation of 17β-hydroxysteroid dehydrogenase (17β-HSD) in vitro. The aim of this study was to verify this hypothesis in vivo. The present study tested the hypothesis that subacute exposure to DEHP induced ovarian dysfunction by dysregulating 17β-HSD signalling. 48 adult female Wistar rats were divided into 4 groups randomly: control group, low-dose group, medium-dose group, and high-dose group. DEHP was intragastrically administrated at the dosage of 0, 300, 1000 and 3000 mg/kg/d (body weight) for 4 weeks. Rats were executed, and the detection of the pathological changes of ovaries, steroid hormone levels, steroid receptor expression, and steroidogenic enzyme expression in sex hormone synthesis pathway and the apoptosis of GCs were performed. This study showed that DEHP could prolong the estrous cycle, increase follicular atresia, inhibit sex hormone secretion, reduce the expression of steroidogenic enzymes, and promote GCs apoptosis associating with ovarian dysfunction. In conclusion, these results indicate that DEHP can disturb ovarian function through the 17β-HSD signalling pathway.

Keywords: 17β-HSD; Di-(2-ethylhcxyl) phthalate; In vivo; Ovarian dysfunction.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases
  • Animals
  • Diethylhexyl Phthalate / pharmacology*
  • Female
  • Rats
  • Rats, Wistar

Substances

  • Diethylhexyl Phthalate
  • 17-Hydroxysteroid Dehydrogenases