An Junqing, Liu Tianlong, She Ruiping, Wu Qiaoxing, Tian Jijing, Shi Ruihan, Hao Wenzhuo, Ren Xinxin, Yang Yue, Lu Yiyao, Yang Yifei, Wu Yuanheng
Laboratory of Veterinary Pathology and Public Health, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China.
Oncotarget. 2017 Dec 17;9(4):4475-4484. doi: 10.18632/oncotarget.23381. eCollection 2018 Jan 12.
Hepatitis E virus (HEV) infection can induce infertility and miscarriage in pregnant women and infect neonates through vertical transmission. However, the mechanism of infertility and vertical transmission remains unclear. In the present study, we evaluated the replication of HEV in the ovary and structural and molecular changes induced by HEV after intraperitoneal injection of HEV in rabbits. Positive- and negative-strand HEV RNA was detected in the ovaries at 28 and 49 days post-infection. Positive HEV open reading frames 2 and 3 signals were observed in the ovaries by immunohistochemistry staining. Histopathological changes of ovarian tissues were observed, including scattered cell necrosis and lymphocyte infiltration. The ratio of normal follicles decreased, whereas the ratio of atresia follicles increased in the HEV RNA-positive ovaries compared to the control group by counting the number of follicles at all levels. In addition, TUNEL results showed that apoptosis in follicle cells and oocytes was promoted by HEV infection. These results suggest that the ovary is one of the replication sites of HEV and that the expression of HEV RNA and antigen in ovarian tissue caused structural and molecular changes that promoted germ cell apoptosis. HEV can infect and replicate in the ovum at different stages, which is a novel mechanism for HEV vertical transmission.
戊型肝炎病毒（HEV）感染可导致孕妇不孕和流产，并通过垂直传播感染新生儿。然而，不孕和垂直传播的机制仍不清楚。在本研究中，我们评估了HEV在卵巢中的复制情况，以及在兔腹腔注射HEV后HEV诱导的结构和分子变化。在感染后28天和49天的卵巢中检测到正链和负链HEV RNA。通过免疫组织化学染色在卵巢中观察到阳性的HEV开放阅读框2和3信号。观察到卵巢组织的组织病理学变化，包括散在的细胞坏死和淋巴细胞浸润。通过计数各级卵泡数量，与对照组相比，HEV RNA阳性卵巢中正常卵泡的比例降低，闭锁卵泡的比例增加。此外，TUNEL结果显示，HEV感染促进了卵泡细胞和卵母细胞的凋亡。这些结果表明，卵巢是HEV的复制部位之一，HEV RNA和抗原在卵巢组织中的表达引起了促进生殖细胞凋亡的结构和分子变化。HEV可在不同阶段的卵子中感染和复制，这是HEV垂直传播的一种新机制。
