Tian Yu, Zhang Ming-Yu, Zhao Ai-Hong, Kong Li, Wang Jun-Jie, Shen Wei, Li Lan
College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao 266109, China.
Qingdao Academy of Agricultural Sciences, Qingdao 266100, China.
Theranostics. 2021 Mar 5;11(11):5197-5213. doi: 10.7150/thno.58433. eCollection 2021.
Zearalenone (ZEN), a pollutant in our daily diet, seriously threatens the reproductive health of humans and animals. The primordial follicle (PF) assembly in the mouse occurs during the perinatal period, which determines the whole ovarian reserve in reproductive lifespan. In the current investigation, we administered ZEN orally to perinatal mice from 16.5 days post coitum (dpc) to postnatal day 3 (PD3), and single-cell RNA sequencing (scRNA-seq) was performed on PD0 and PD3 ovarian tissues in the offspring to check ZEN toxic to primordial follicle formation at the single cell level. Ovarian tissues () were examined by single cell RNA sequencing analysis, Immunostaining, and Western blotting. Ovarian tissues () were examined by qRT-PCR, Immunostaining, and Western blotting. We found that ZEN exposure altered the developmental trajectory of both germ cells and granulosa cells. Furthermore, after establishing the cell-cell communication network between germ cells and granulosa cells, we found that this was perturbed by ZEN exposure, especially during the Hippo signaling pathway. This study showed that ZEN affected the status of germ cells and granulosa cells through the Hippo signaling pathway and blocked the assembly of PFs. This research contributes to our deeper understanding of the mechanisms of toxicity in different cell types and the disruption of normal intercellular signaling by ZEN exposure.
玉米赤霉烯酮（ZEN）是我们日常饮食中的一种污染物，严重威胁着人类和动物的生殖健康。小鼠原始卵泡（PF）的组装发生在围产期，这决定了其生殖寿命中的整个卵巢储备。在本研究中，我们从交配后16.5天（dpc）至出生后第3天（PD3）对围产期小鼠进行ZEN口服给药，并对后代小鼠出生当天（PD0）和出生后第3天（PD3）的卵巢组织进行单细胞RNA测序（scRNA-seq），以在单细胞水平上检查ZEN对原始卵泡形成的毒性。通过单细胞RNA测序分析、免疫染色和蛋白质免疫印迹法对卵巢组织进行检测。通过qRT-PCR、免疫染色和蛋白质免疫印迹法对卵巢组织进行检测。我们发现，ZEN暴露改变了生殖细胞和颗粒细胞的发育轨迹。此外，在建立生殖细胞和颗粒细胞之间的细胞-细胞通讯网络后，我们发现这一网络受到ZEN暴露的干扰，尤其是在Hippo信号通路中。本研究表明，ZEN通过Hippo信号通路影响生殖细胞和颗粒细胞的状态，并阻断原始卵泡的组装。这项研究有助于我们更深入地了解不同细胞类型的毒性机制以及ZEN暴露对正常细胞间信号传导的破坏。
