The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China.
The Affiliated Hospital, Guizhou Medical University, Guiyang, Guizhou, China.
PLoS One. 2018 Aug 2;13(8):e0201136. doi: 10.1371/journal.pone.0201136. eCollection 2018.
Cyclophosphamide (CTX) has immunosuppressive effects and has been wildly used as one anti-cancer drug in clinical. Significant toxicity has been noticed particularly in the reproductive system. CTX promotes the maturation of ovarian follicles, decreases follicular reserve, and ultimately lead to ovarian failure or even premature ovarian failure (POF). The placental extract (HPE) has been shown to have some beneficial impact on reproductive system; however, little is known regarding to the effect of HPE on protecting CTX-induced ovarian injury and the mechanism involved. Whether human placental extracts (HPE) has a protective effect on CTX-induced toxicity on ovarian was studied by using a CTX-induced ovarian injury animal model. The effects of HEP on histopathology, the number of atretic follicles, the weight of the ovary, serum hormone levels, and apoptosis in granulosa cells were studied in mice with CTX or control vehicle. Our results have demonstrated that HPE inhibited p-Rictor, reduced the expression of Bad, Bax and PPAR, and activated Akt and Foxo3a (increased their phosphorylation). Mice treated with HPE showed higher ovarian weight, lower number of atretic follicles, higher serum levels of the hormones E2 and progesterone, and lower apoptosis and serum levels of LH and FSH in granulosa cells, than that in the control animal group. Our data show that ovarian injury can be attenuated by HPE. HPE likely protects follicular granulosa cells from undergoing significant apoptosis and reduce atresia follicle formation, therefore, alleviates CTX-induced ovarian injury.
环磷酰胺（CTX）具有免疫抑制作用，已广泛应用于临床抗癌药物。尤其在生殖系统方面，CTX 具有明显的毒性。CTX 促进卵泡成熟，减少卵泡储备，最终导致卵巢衰竭甚至早发性卵巢功能衰竭（POF）。胎盘提取物（HPE）已被证明对生殖系统有一定的有益影响；然而，对于 HPE 对 CTX 诱导的卵巢损伤的保护作用及其相关机制知之甚少。本研究通过建立 CTX 诱导的卵巢损伤动物模型，探讨 HPE 是否对 CTX 诱导的卵巢毒性具有保护作用。研究 HEP 对 CTX 或对照药物处理的小鼠卵巢组织病理学、闭锁卵泡数、卵巢重量、血清激素水平和颗粒细胞凋亡的影响。我们的研究结果表明，HPE 抑制了 p-Rictor，降低了 Bad、Bax 和 PPAR 的表达，激活了 Akt 和 Foxo3a（增加了它们的磷酸化）。与对照组相比，HPE 处理的小鼠卵巢重量更高，闭锁卵泡数量更少，血清中 E2 和孕激素水平更高，颗粒细胞凋亡和血清中 LH 和 FSH 水平更低。这些数据表明，HPE 可以减轻卵巢损伤。HPE 可能通过防止卵泡颗粒细胞发生明显凋亡和减少闭锁卵泡形成，从而减轻 CTX 诱导的卵巢损伤。
