Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

Abstract

Rationale: 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. Methods: Ovarian tissues ( in vivo ) were examined by single cell RNA sequencing analysis, Immunostaining, and Western blotting. Ovarian tissues ( in vitro ) were examined by qRT-PCR, Immunostaining, and Western blotting. Results: 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. Conclusions: 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.

Protective Mechanism of Luteinizing Hormone and Follicle-Stimulating Hormone Against Nicotine-Induced Damage of Mouse Early Folliculogenesis

“…At this point, there are still plenty of oocytes remaining in the ovarian cysts. Consistent with previous studies Liu et al, 2019;Liu W. X. et al, 2021;Tian et al, 2021;Wang et al, 2021), the effect of the drug on germ cell cyst breakdown and PF formation could be measured by counting the proportion of oocytes in cysts and follicles. In addition, newborn mice were fed normally after 4 days of intraperitoneal injection.…”

The Effects of Zearalenone on the Localization and Expression of Reproductive Hormones in the Ovaries of Weaned Gilts

“…It is well-documented that as an exogenous estrogen, ZEA can cause hyperestrogenism in pigs [ 12 ]. The clinical symptoms of hyperestrogenism were vulva swelling, prolonged oestrus, anal prolapse and high incidence of stillbirth [ 29 , 30 , 31 ]. Fu et al [ 32 ] reported that dietary ZEA (1.20 mg/kg) significantly increased vulva width and length of piglets compared to the control group.…”

Impaired primordial follicle assembly in offspring ovaries from zearalenone-exposed mothers involves reduced mitochondrial activity and altered epigenetics in oocytes

“…Sample preparation for sequencing: The method was the same as previously described [33]. Sample preparation for the experiment: At PD0 and PD3, ovaries were separated from mouse ovarian capsules in 0.9% normal saline.…”

“…Interestingly, applying new single-cell RNA sequencing (scRNA-seq) technology, Tian et al recently suggested that altered oxidative phosphorylation and DNA damage in oocytes can affect PF formation after ZEA exposure. In fact, they showed that maternal exposure to ZEA changed the developmental status of mouse oocytes and granulosa cells in offspring ovaries and altered the expression of genes associated with intercellular communication, oxidative phosphorylation, and DNA damage in oocytes [33]. Besides ROS generation, damage to mitochondrial activities can deregulate other relevant molecular pathways, including those involved in general cellular metabolism and gene expression [34,35].…”