Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Abstract

The interaction of granulosa cells (GCs) with oocytes is important to regulate follicle development. The exogenous melatonin promoting the maturation of oocytes by GCs has been approved in pig, however, the transcriptome profile and the functions of the genes regulated by melatonin in GCs have not yet to be fully characterized. In this study, we found melatonin could stimulate the synthesis of estradiol in pig GCs. The RNA‐seq was used to explore the effects of melatonin on gene expression, a total of 89 differentially expressed genes (DEGs) were identified. Gene ontology analysis showed DEGs which associated with regulation of cell proliferation, cell cycle, and anti‐apoptosis were significantly enriched. The functions of two DEGs, NOTCH2 and FILIP1L, were studied in pig GCs. The results showed that NOTCH2 inhibited the synthesis of estradiol, but FILIP1L promoted the synthesis of estradiol. Furthermore, inhibiting NOTCH2 in granulosa cells cocultured with cumulus‐oocyte‐complexes had no obvious effect on the maturation of pig oocyte, but could upregulate the cleavage rate of oocyte. We proved that FILIP1L had no effect on the maturation and cleavage of pig oocytes. Our work deepens the understanding of melatonin's effects on GCs and oocyte. The DEGs we found will be beneficial to reveal mechanisms of melatonin acting on GCs and oocytes and design the pharmacological interventions.

Quercetin Protects against Lipopolysaccharide-Induced Intestinal Oxidative Stress in Broiler Chickens through Activation of Nrf2 Pathway

“…The reason may be that 500 mg/kg of quercetin is far beyond the effective range of quercetin to exert its role. Correspondingly, it has been demonstrated in other antioxidant studies that antioxidant effects are in a dose-dependent manner [28,29]. The present results will provide reference for the use of quercetin as a feed additive to protect broiler intestinal health.…”

Melatonin Inhibits Apoptosis and Oxidative Stress of Mouse Leydig Cells via a SIRT1-Dependent Mechanism

“…Treatment of mouse granulosa cells with 0.1, 1, 10, and 100 μM of melatonin revealed that the optimal concentration to inhibit palmitic acid-induced apoptosis was 10 μM, rather than 100 μM [11]. In pig granulosa cells, a low concentration (0.1 μM) of melatonin instead of the high concentration (10 μM) stimulates the synthesis of estradiol and produces differentially expressed genes, which are associated with regulation of cell proliferation, cell cycle, and anti-apoptosis [34]. These results support our findings.…”

Transcriptomic Data Analyses Reveal That Sow Fertility-Related lincRNA NORFA Is Essential for the Normal States and Functions of Granulosa Cells

“…It has been well documented that 17β-estradiol (E2), the principal form of estrogens, is produced by adrenals and ovarian GCs and crucial for estrus cycle, ovarian development, follicular maturity, and ovulation (Baerwald et al, 2012;Herbison, 2020). E2 secretion is the most important function of female ovarian GCs, which also feedback regulates the transcriptome and the states (such as proliferation and apoptosis) of GCs in an autocrine manner (Ciesiolka et al, 2017;Liu et al, 2019). In recent years, E2 synthesis in female ovarian GCs has been proved to be regulated by a bunch of epigenetic regulation factors including miRNAs, circRNAs, and lncRNAs (Li et al, 2018a;Huang et al, 2020).…”