Abstract
H3K27me3 is an epigenetic modification that results in the repression of gene transcription. The transcription factor RUNX1 (the runt-related transcription factor 1) influences granulosa cells’ growth and ovulation. This research uses ELISA, flow cytometry, EDU, ChIP-PCR, WB and qPCR to investigate steroidogenesis, cell apoptosis, and the proliferation effect of RUNX1 in porcine granulosa cells (pGCs) as regulated by H3K27me3. Decreased H3K27me3 stimulates the expression of steroidogenesis-related genes, including CYP11A1, PTGS2, and STAR, as well as prostaglandin. H3K27me3 transcriptionally represses RUNX1 here, whereas RUNX1 acts as an activator of FSHR, CYP11A1, and CYP19A1, promoting the production of androgen, estrogen, and prostaglandin, as well as increasing anti-apoptotic and cell proliferation activity, but decreasing progesterone. Both the complementary recovery of the H3K27me3 antagonist with the siRUNX1 signal, and the H3K27me3 agonist with the RUNX1 signal to maintain RUNX1 lead to the activation of CYP19A1, ER1, HSD17β4, and STAR here. Androgen and prostaglandin are significantly repressed but progesterone is markedly increased with the antagonist and siRUNX1. Prostaglandin is significantly promoted with the agonist and RUNX1. Furthermore, H3K27me3-RUNX1 affects the anti-apoptotic activity and stimulation of proliferation in pGCs. The present work verifies the transcriptional suppression of RUNX1 by H3K27me3 during antral follicular development and maturation, which determines the levels of hormone synthesis and cell apoptosis and proliferation in the pGC microenvironment.
Highlights
The ovary is an important organ in the female reproductive system which is responsible for follicular growth, ovulation, and the synthesis of sexual hormones under the regulation of the hypothalamic–pituitary–gonadal (HPG) axis
Growth hormones are classical paracrine and endocrine factors in Granulosa cells (GCs) that regulate steroidogenesis, folliculogenesis, oocyte maturation, and the response to human menopausal gonadotropin stimulation in the induction of ovulation [11]. Steroidogenesis is another main function of GCs in response the stimulation of the FSH and LH, maintaining follicle growth and causing oocyte maturation and ovulation to proceed, alongside estrogen, androstenedione, testosterone and progesterone [12], and in addition to prostaglandin E2 (PGE)/F2α (PGF) [13]
RUNX1 dynamically increases during antral follicular growth and maturation, resulting from the gradually released transcriptional repression of H3K27me3
Summary
The ovary is an important organ in the female reproductive system which is responsible for follicular growth, ovulation, and the synthesis of sexual hormones under the regulation of the hypothalamic–pituitary–gonadal (HPG) axis. Growth hormones are classical paracrine and endocrine factors in GCs that regulate steroidogenesis, folliculogenesis, oocyte maturation, and the response to human menopausal gonadotropin (hMG) stimulation in the induction of ovulation [11]. Steroidogenesis is another main function of GCs in response the stimulation of the FSH and LH, maintaining follicle growth and causing oocyte maturation and ovulation to proceed, alongside estrogen, androstenedione, testosterone and progesterone [12], and in addition to prostaglandin E2 (PGE)/F2α (PGF) [13].
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