Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; Jiangxi Key Laboratory of Reproductive Physiology and Pathology, Nanchang University, Nanchang, Jiangxi 330031, China.
Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China; The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330031, China.
Reprod Toxicol. 2019 Jan;83:21-27. doi: 10.1016/j.reprotox.2018.10.007. Epub 2018 Nov 13.
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.
磷酸三邻甲苯酯（TOCP）作为一种广泛应用于社会的增塑剂，据报道其能够抑制精子发生和精原干细胞的生长。然而，其对女性生殖系统的影响尚不清楚。本研究通过慢性 TOCP 暴露的小鼠模型，探讨了 TOCP 对卵泡发育的影响，并检测了 Hippo 通路的核心组成部分的表达，该通路已被证明对卵泡发育至关重要。此外，通过上调卵巢中的 Hippo-yes 相关蛋白 1（Yap1），观察 Yap1 过表达对 TOCP 诱导的卵巢功能障碍的潜在保护作用。结果表明，TOCP 以剂量依赖的方式损害卵巢功能，且 Hippo 通路的表达在 TOCP 暴露的卵巢中发生显著改变。此外，YAP1 过表达部分逆转了 TOCP 诱导的卵巢损伤。综上所述，这些数据表明 Hippo 通路参与了 TOCP 引起的卵巢功能障碍的机制。
