Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats

Iran J Basic Med Sci. 2018 Aug;21(8):848-855. doi: 10.22038/IJBMS.2018.28489.6905.

Abstract

Objectives: Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in different kinds of commercial products as a plasticizer. Previous studies have revealed that exposures to DEHP could be associated with precocious puberty in teenagers, but the exact mechanism is yet to be known.

Materials and methods: In this study, 48 prepubertal Wistar female rats were randomly apportioned into 4 groups and orally treated with 0, 250, 500, and 1000 mg/kg/d DEHP from postnatal day 21 up to 4 weeks. Subsequently, we examined the indicators related to the initiation of sexual development.

Results: DEHP was able to shorten the vaginal opening time and prolong the estrous cycles of female rats. IGF-1 expression was significantly upregulated by 1000 mg/kg/d DEHP in the hypothalamus, and the hypothalamic, as well as serum levels of GH, were also upregulated by DEHP. It also caused decrements in serum levels of FSH, LH, and T and the increment in level of progesterone. Meanwhile, DEHP was able to exert its effect on the mRNA and protein expression levels of Kiss-1, GPR54, and GnRH in the hypothalamus in pubertal female rats.

Conclusion: These findings are revealing that DEHP exposure more likely causes imbalances of hypothalamus functioning in pubertal female rats and thus induces precautious puberty in these animals.

Keywords: Di-(2-ethylhexyl) phthalate; Female; Hypothalamus; Precocious puberty; Reproductive.