chi-miR-130b-3p regulates the ZEA-induced oxidative stress damage through the KEAP1/NRF2 signaling pathway by targeting SESN2 in goat GCs.

As a dominant mycotoxin, zearalenone (ZEA) has attracted extensive attention due to its estrogen-like effect and oxidative stress damage in cells. In order to find a way to relieve cell oxidative stress damage caused by ZEA, we treated goat granulosa cells (GCs) with ZEA and did a whole transcriptome sequencing. The results showed that the expression level of Sesterin2 (SESN2) was promoted extremely significantly in the ZEA group (p < .01). In addition, our research demonstrated that SESN2 could regulate oxidative stress level in GCs through Recombinant Kelch Like ECH Associated Protein 1 (KEAP1)/Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. The overexpression of SESN2 could reduce the oxidative damage, whereas knockdown of SESN2 would aggravate the oxidative damage caused by ZEA. What's more, microRNA (miRNA) chi-miR-130b-3p can bind to SESN2 3'-untranslated region (3'UTR) to regulate the expression of SESN2. The mimics/inhibition of chi-miR-130b-3p would have an effect on oxidative damage triggered by ZEA in GCs as well. In summary, these results elucidate a new pathway by which chi-miR-130b-3p affects the KEAP1/NRF2 pathway in GCs by modulating SESN2 expression in response to ZEA-induced oxidative stress damage.

Melatonin protects Leydig cells from HT-2 toxin-induced ferroptosis and apoptosis via glucose-6-phosphate dehydrogenase/glutathione -dependent pathway.

HT-2 toxin is a mycotoxin commonly found in food and water that can have adverse effects on male reproductive systems, including testosterone secretion. Ferroptosis and apoptosis are two types of programmed cell death that have been implicated in the regulation of cellular functions. Melatonin, a powerful antioxidant with various physiological functions, has been shown to regulate testosterone secretion. However, the mechanisms underlying the protective effects of melatonin against HT-2 toxin-induced damage in testosterone secretion are not fully understood. In this study, we investigated the effects of HT-2 toxin on sheep Leydig cells and the potential protective role of melatonin. We found that HT-2 toxin inhibited cell proliferation and testosterone secretion of Leydig cells in a dose-dependent manner and induced ferroptosis and apoptosis through intracellular reactive oxygen species accumulation, leading to lipid peroxidation. Exposure of Leydig cells to melatonin in vitro reversed the defective phenotypes caused by HT-2 toxin via a glucose-6-phosphate dehydrogenase/glutathione-dependent mechanism. Interference of glucose-6-phosphate dehydrogenase disrupted the beneficial effect of melatonin on ferroptosis and apoptosis in HT-2 toxin-treated Leydig cells. Furthermore, similar results were observed in vivo in the testes of male mice injected with HT-2 toxin with or without melatonin treatment for 30 days. Our findings suggest that melatonin inhibits ferroptosis and apoptosis by elevating the expression of glucose-6-phosphate dehydrogenase to eliminate reactive oxygen species accumulation in HT-2 toxin-treated Leydig cells. These results provide fundamental evidence for eliminating the adverse effects of HT-2 toxin on male reproduction.

Long non-coding RNA366.2 controls endometrial epithelial cell proliferation and migration by upregulating WNT6 as a ceRNA of miR-1576 in sheep uterus.

Long non-coding RNAs (lncRNAs) play an important regulatory role in mammalian fecundity. Currently, most studies are primarily concentrated on ovarian lncRNAs, ignoring the influence of uterine lncRNAs on the fecundity of female sheep. In this study, we found a higher density of uterine glands and endometrial microvessel density (MVD) in high prolificacy group of Hu sheep compared to low prolificacy groups (p < 0.05) as well as an increased level of serum placental growth factor (PLGF). Hundreds of differentially expressed (DE) lncRNAs were identified in Hu sheep with different fecundity by RNA sequencing (RNA-seq), and their targets were enriched in some signaling pathways involved in endometrial functions, such as the estrogen signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, oxytocin signaling pathway, and Wnt signaling pathway. Furthermore, the underlying mechanisms of competitive endogenous RNA (ceRNA) of lncRNA366.2-miR-1576- WNT6 were determined by bioinformatics analysis. Functionally, our results indicated that lncRNA366.2 promoted endometrial epithelial cell (EEC) proliferation, migration, and growth factor expression by sponging miR-1576 to upregulate WNT6 expression and activate the Wnt/ß-catenin pathway. Taken together, our research indicated the regulatory mechanism of the lncRNA366.2-miR-1576-WNT6 in EEC proliferation and migration. Furthermore, this study provides a new theoretical reference for the identification of candidate genes related to fecundity.