Microarray analysis of differentially expressed microRNAs in non-regressed and regressed bovine corpus luteum tissue; microRNA-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene

Abstract

MicroRNAs (miRNAs) are small non-coding endogenous RNA molecules that down-regulate the expression of target genes in a sequence-dependent manner. Recent studies indicated that miRNAs are mechanistically involved in the regulation of the mammalian corpus luteum (CL). However, few studies have profiled the different miRNA expression patterns in bovine non-regressed and regressed CL. In this study, miRNA microarray was employed to investigate the different miRNA expression patterns in bovine CL. Among the 13 differentially expressed miRNAs, seven were preferentially expressed in non-regressed CL, while six miRNAs were more highly expressed in regressed CL. Real-time RT-PCR was used to validate the microarray results. Mir-378 miRNA, known to be associated with apoptosis, was 8.54-fold (P < 0.01) up-regulated in non-regressed CL, and the interferon gamma receptor 1 (IFNGR1) gene, which potentially plays a role in apoptosis of the luteal cell, was predicted to be the target of mir-378. The results of real-time RT-PCR of mir-378 and western blot analysis of the IFNGR1 protein at different stages of CL development showed that mir-378 decreased the expression of IFNGR1 protein but not IFNGR1 mRNA. Taken together, our data support a direct role for miRNA in apoptosis of bovine CL.

MicroRNA-378 regulates oocyte maturation via the suppression of aromatase in porcine cumulus cells

“…Ma et al (32) reported the inversed expression between miR-378 and the interferon-␥ receptor 1 (IFNGR1) gene, a predicted target of miR-378 during corpus luteum development. Highly upregulated miR-378 expression in nonregressed bovine corpus luteum suggested a potential role for miR-378 in suppressing luteal cell apoptosis via IFNGR1 suppression (32). Whether miR-378 specifically targets IFNGR1 transcripts in cumulus cells remains unknown, but these studies provide evidence that this miRNA may perform important functions in ovarian cell differentiation and development.…”

MicroRNA in Ovarian Biology and Disease

“…Quantitative RT-PCR studies confirmed high levels of miR-378 and IFNGR1 mRNA in the CL at middle and late stages of CL maintenance, but much lower levels of miR-378 in the regressing CL. Although there was no change in the levels of IFNGR1 mRNA during luteal regression, there was a significant increase in protein expression supporting the likelihood of posttranscriptional regulation of IFNGR1 (Ma et al 2011). Interestingly, miR-378 has also been reported to down-regulate CYP19 expression in porcine granulosa cells (Xu et al 2011b).…”

“…Several studies have characterized miRNA expression in different compartments of the adult ovary, including during periods of follicle development, oocyte maturation, and luteal function (Ro et al 2007;Fiedler et al 2008;Otsuka et al 2008;Hossain et al 2009;Yao et al 2010;Ma et al 2011;da Silveira et al 2012;McBride et al 2012;Yin et al 2012). However, the majority of studies examining the role of miRNAs in the regulation of follicle growth have focused on granulosa cells (Christenson 2010).…”

“…However, this single dose treatment was not able to maintain pregnancy, suggesting that other factors are likely also involved or that long-term/repeated inhibition would be needed to induce a sustained longterm effect (Otsuka et al 2008). Ma et al (2011) used a bovine model to compare miRNA expression patterns of fully functional CL producing high levels of progesterone versus CL undergoing regression (Ma et al 2011). Not surprisingly, marked differences in miRNA expression were observed.…”

In search of the transcriptional blueprints of a competent oocyte

“…They are found in the diverse compartments of ovarian follicles, including granulosa cells (Hatzirodos et al, 2014a), theca cells (Hatzidoros et al, 2014b), follicular fluid and oocytes (Bonnet et al, 2008). Studies demonstrated their role in follicle development of humans (Sirotkin et al, 2009;Sang et al, 2013;Roth et al, 2014), mice (Fiedler et al, 2008;Carletti et al, 2010), cattle (Tesfaye et al, 2009;Ma et al, 2011;Sohel et al, 2013), pigs (Lin et al, 2012;Donadeu and Schauer, 2013) and horses (Da Silveira et al, 2012). Data suggest that miRNAs may regulate cellular differentiation during follicular development and may contribute to the oocyte-somatic cells dialog during the acquisition of oocyte developmental competence.…”