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Reprod Toxicol. 2019 Jan;83:21-27. doi: 10.1016/j.reprotox.2018.10.007. Epub 2018 Nov 13.

Tri-ortho-cresyl phosphate (TOCP) induced ovarian failure in mice is related to the Hippo signaling pathway disruption.

Author information

1
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; Jiangxi Key Laboratory of Reproductive Physiology and Pathology, Nanchang University, Nanchang, Jiangxi 330031, China.
2
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330031, China.
3
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; School of the First Clinical Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China.
4
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; School of the Second Clinical Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, PR China.
5
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; Jiangxi Key Laboratory of Reproductive Physiology and Pathology, Nanchang University, Nanchang, Jiangxi 330031, China. Electronic address: zhengliping@ncu.edu.cn.

Abstract

As a plasticizer widely used in society, tri-ortho-cresyl phosphate (TOCP) is reported to inhibit spermatogenesis and growth of spermatogonial stem cells. However, its effects on female reproductive system are virtually unknown. The present study investigated the effects of TOCP on ovarian follicle development by using mouse model of chronic TOCP exposure, and examined the expression of the core components of the Hippo pathway, which had been proven to be crucial for ovarian follicle development. Furthermore, through up-regulation of Hippo-yes-associated protein 1 (Yap1) in ovaries, the potential protective effects of Yap1 over-expression on TOCP-induced ovarian dysfunction were observed. The results showed that TOCP impaired ovarian function in a dose-dependent manner, and the expression of the Hippo pathway changed significantly in TOCP-exposed ovaries. Further, YAP1 over-expression partially reversed the TOCP-induced ovarian impairment. Collectively, these data indicate that the Hippo pathway is involved in the mechanism by which TOCP elicits ovarian function impairment.

KEYWORDS:

Hippo pathway; Ovarian function; Plasticizer; Reproductive toxicity; Tri-ortho-cresyl phosphate

PMID:
30439503
DOI:
10.1016/j.reprotox.2018.10.007
[Indexed for MEDLINE]

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