Developmental and hormonal regulation of ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 gene expression in ovarian granulosa and theca cells of cattle

Abstract

<jats:title>Abstract</jats:title> <jats:p>Ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) is a multi-domain nuclear protein that plays an important role in epigenetics and tumorigenesis, but its role in normal ovarian follicle development remains unknown. Thus, the present study evaluated if UHRF1 mRNA abundance in bovine follicular cells is developmentally and hormonally regulated, and if changes in UHRF1 are associated with changes in DNA methylation in follicular cells. Abundance of UHRF1 mRNA was greater in granulosa cells (GC) and theca cells (TC) from small (&amp;lt;6 mm) than large (≥8 mm) follicles, and was greater in small-follicle GC than TC. In GC and TC, FGF9 treatment increased (P &amp;lt; 0.05) UHRF1 expression by twofold. Also, luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1) increased (P &amp;lt; 0.05) UHRF1 expression in TC by twofold, and forskolin (an adenylate cyclase inducer) alone or combined with IGF1 increased (P &amp;lt; 0.05) UHRF1 expression by threefold. An E2F transcription factor inhibitor (E2Fi) decreased (P &amp;lt; 0.05) UHRF1 expression by 44% in TC and by 99% in GC. Estradiol, progesterone and dibutyryl-cAMP decreased (P &amp;lt; 0.05) UHRF1 mRNA abundance in GC. Treatment of GC with FSH alone had no effect but combined with IGF1 enhanced UHRF1 mRNA abundance by 2.7-fold. Beauvericin (a mycotoxin) completely inhibited the FSH plus IGF1-induced UHRF1 expression in small-follicle GC. Treatments that increased UHRF1 mRNA (i.e., FGF9) in GC tended to decrease (by 63%; P &amp;lt; 0.10) global DNA methylation, and those that decreased UHRF1 mRNA (i.e., E2Fi) in GC tended to increase (by 2.4-fold; P &amp;lt; 0.10) global DNA methylation. Collectively, these results suggest that UHRF1 expression in both GC and TC is developmentally and hormonally regulated, and that UHRF1 may play a role in follicular growth and development as well as be involved in ovarian epigenetic processes.</jats:p>

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

“…Previous studies evaluating the effects of Fusarium mycotoxins on granulosa cell proliferation show that fumonisin B1 and beauvericin reduce cell growth after 24 h and 48 h of treatment [ 23 , 24 ] but the mechanism of inhibition was not evaluated. A recent study has reported that beauvericin reduces the mRNA abundance of ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1), a multi-domain nuclear protein that plays an important role in DNA repair and DNA replication controlling the onset of S phase [ 30 ], but whether ENNA affects GC proliferation via UHRF1 will require further study. Further work will also be required to determine the stage of the cell cycle that is disrupted by ENNA as well as evaluate if ENNA activates programmed cell death.…”

Emerging mycotoxins and reproductive effects in animals: A short review

“…Even if there is currently no sufficient toxico‐epidemiological data that confirm effects of BEA on farm animal reproduction, some recent studies established that BEA may affect ovarian function in sows (Mallebrera et al, 2018; Santos et al, 2015) and cattle (Albonico et al, 2017; Perego et al, 2020). Schoevers et al (2016) reported an impaired development of in vitro cultured porcine oocytes and embryos after exposure to BEA.…”

“…However, concentrations of BEA at ≤1.5 μM had no effect on steroid production by bovine granulosa cells (Albonico et al, 2017). Perego et al (2020) reported that 30 μM BEA completely inhibited the FSH plus IGF1‐induced UHRF1 mRNA expression in bovine granulosa cells. BEA has been detected in feed products in concentrations ranging from few units to hundreds of μg/kg with a prevalence of 62% (Tolosa et al, 2019), suggesting that BEA may represent a risk for animal health affecting reproductive functions.…”