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Open AccessArticle

Effects of Di-(2-ethylhexyl) Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats

by Te Liu 1,2,†, Yiyang Jia 1,†, Liting Zhou 1, Qi Wang 1, Di Sun 1, Jin Xu 1, Juan Wu 3, Huaiji Chen 1, Feng Xu 1 and Lin Ye 1,*
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun 130021, China
Scientific Research Center, China Japan Union Hospital, Jilin University, Changchun 130000, China
Prevention and Health Section, Jiangxi Provincial Cancer Hospital, Nanchang 330000, China
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Academic Editor: William A. Toscano
Int. J. Environ. Res. Public Health 2016, 13(11), 1130;
Received: 19 September 2016 / Revised: 26 October 2016 / Accepted: 7 November 2016 / Published: 12 November 2016
(This article belongs to the Section Environmental Health)
The pollution of endocrine disruptors and its impact on human reproductive system have attracted much attention. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely used in food packages, containers, medical supplies and children’s toys. It can cause diseases such as infertility, sexual precocity and uterine bleeding and thus arouse concerns from the society and scholars. The effect of DEHP on pubertal female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on the hypothalamus–uterus in pubertal female rats, reveal the reproductive toxicity of DEHP on pubertal female rats and its mechanism, and provide scientific evidence for the evaluation of toxicity and toxic mechanism of DEHP on reproductive system. Forty-eight pubertal female rats were randomly divided into four groups and respectively administered via oral gavage 0, 250, 500, or 1000 mg/kg/d DEHP in 0.1 mL corn oil/20 g body weight for up to four weeks. Compared with control rats, the DEHP-treated rats showed: (1) higher gonadotropin-releasing hormone (GnRH) level in the hypothalamus; (2) higher protein levels of GnRH in the hypothalamus; and (3) higher mRNA and protein levels of GnRH receptor (GnRHR) in the uterus. Our data reveal that DEHP exposure may lead to a disruption in pubertal female rats and an imbalance of hypothalamus–uterus. Meanwhile, DEHP may, through the GnRH in the hypothalamus and its receptor on the uterus, lead to diseases of the uterus. DEHP may impose a negative influence on the development and functioning of the reproductive system in pubertal female rats. View Full-Text
Keywords: di-(2-ethylhcxyl) phthalate; hypothalamus; uterus; reproductive toxicity; pubertal di-(2-ethylhcxyl) phthalate; hypothalamus; uterus; reproductive toxicity; pubertal
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Liu, T.; Jia, Y.; Zhou, L.; Wang, Q.; Sun, D.; Xu, J.; Wu, J.; Chen, H.; Xu, F.; Ye, L. Effects of Di-(2-ethylhexyl) Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats. Int. J. Environ. Res. Public Health 2016, 13, 1130.

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