ERK1/2-dependent gene expression in the bovine ovulating follicle

Abstract

Ovulation is triggered by gonadotropin surge-induced signaling cascades. To study the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in bovine ovulation, we administered the pharmacological inhibitor, PD0325901, into the preovulatory dominant follicle by intrafollicular injection. Four of five cows treated with 50 µM PD0325901 failed to ovulate. To uncover the molecular basis of anovulation in ERK1/2-inhibited cows, we collected granulosa and theca cells from Vehicle and PD0325901 treated follicles. Next-generation sequencing of granulosa cell RNA revealed 285 differentially expressed genes between Vehicle and PD0325901-treated granulosa cells at 6 h post-GnRH. Multiple inflammation-related pathways were enriched among the differentially expressed genes. The ERK1/2 dependent LH-induced genes in granulosa cells included EGR1, ADAMTS1, STAT3 and TNFAIP6. Surprisingly, PD0325901 treatment did not affect STAR expression in granulosa cells at 6 h post-GnRH. Granulosa cells had higher STAR protein and theca cells had higher levels of STAR mRNA in ERK1/2-inhibited follicles. Further, both granulosa and theca cells of ERK1/2-inhibited follicles had higher expression of SLC16A1, a monocarboxylate transporter, transporting substances including β-hydroxybutyrate across the plasma membrane. Taken together, ERK1/2 plays a significant role in mediating LH surge-induced gene expression in granulosa and theca cells of the ovulating follicle in cattle.

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

“…Substantial evidence has shown that EGF-like factors (AREG, EREG, BTC), EGFR and the ERK1/ERK2 signaling cascade have critical roles for cumulus expansion, oocyte maturation, and follicle rupture. Many genes related to ovulation including AREG, EREG, HAS2, PTGS2, CITED2, CITED4, and ADAMTS1 were induced by LH via the ERK1/ERK2 signaling cascade [6,[52][53][54]. These gene expressions may be essential for oocyte meiotic maturation.…”

“…LH mainly triggers the ERK1/ ERK2 signaling cascade in granulosa cells (GCs) to induce the expression of many genes crucial for ovulation, oocyte meiosis, and extracellular matrix (ECM) remodeling [1]. Many of these ERK1/ERK2-dependent genes, including AREG, ADAMTS1, and CITED2, in GCs were associated with oocyte quality and IVF outcomes [2][3][4][5][6][7].…”

The Expression of ERK1/2 in Female Yak (Bos grunniens) Reproductive Organs

“…Most recently, by injection of pharmacological inhibitor (PD0325901) of ERK1/2 into the pre-ovulatory dominant follicle, Yasmin et al found that four of five cows failed to ovulate, and 285 differentially expressed genes were identified from granulosa cells of drug treated follicles. Based on the analysis of the differentially expressed genes, they further affirmed a significant role of ERK1/2 in mediating LH induced gene expression in ovulating follicles, and the physiological process of ovulation dependent on proper ERK1/2 signaling in bovine [25]. Ryan et al also found that the level of ERK signal proteins was different between dominant and subordinate follicles early in the stage of dominant follicle selection in cows [26].…”

“…In an overall view, the function and mechanism of ERK1/2 vary under different circumstances and physiological statuses [20]. Similarly, some experiments have shown that the expression of ERK1 and ERK2 are widely presented in different parts of the reproductive organs in mammals and poultry [21][22][23][24][25][26][27][28][29][30][31][32]. However, the whole profile and specific role of ERK1/2 expression in reproductive organs, along with the different reproductive cycle stages, have not yet been detected and analyzed clearly in mammals.…”

Polymorphisms in the ASMT and ADAMTS1 gene may increase litter size in goats

“…In the granulosa cells of the preovulatory follicles, ADAMTS1 mRNA expression could be induced by administering luteinizing hormone (LH), and the expression level was sustained in a progesterone-dependent manner (Boerboom, Russell, Richards, & Sirois, 2003;Espey et al, 2000;Robker et al, 2000;Sayasith, Lussier, & Sirois, 2013). ADAMTS1 was one of the extracellular signal-regulated kinase 1/2 (ERK1/2) dependent LH-induced genes (Schuermann et al, 2018) and upregulated in bovine granulosa cells during ovulation (Lussier, Diouf, Levesque, Sirois, & Ndiaye, 2017).…”