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 (<6 mm) than large (≥8 mm) follicles, and was greater in small-follicle GC than TC. In GC and TC, FGF9 treatment increased (P < 0.05) UHRF1 expression by twofold. Also, luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1) increased (P < 0.05) UHRF1 expression in TC by twofold, and forskolin (an adenylate cyclase inducer) alone or combined with IGF1 increased (P < 0.05) UHRF1 expression by threefold. An E2F transcription factor inhibitor (E2Fi) decreased (P < 0.05) UHRF1 expression by 44% in TC and by 99% in GC. Estradiol, progesterone and dibutyryl-cAMP decreased (P < 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 < 0.10) global DNA methylation, and those that decreased UHRF1 mRNA (i.e., E2Fi) in GC tended to increase (by 2.4-fold; P < 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.

中文翻译：

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植物同源结构域和真正有趣的新基因指结构域1基因在牛的卵巢颗粒和卵泡膜细胞中的表达对泛素样蛋白的发育和激素调控。

具有植物同源结构域和真正有趣的新基因指结构域1（UHRF1）的泛素样蛋白是一种多结构域核蛋白，在表观遗传学和肿瘤发生中起重要作用，但其在正常卵泡发育中的作用仍然未知。因此，本研究评估了牛卵泡细胞中UHRF1 mRNA的丰度是否受到发育和激素调节，以及UHRF1的变化是否与卵泡细胞DNA甲基化的变化相关。在小卵泡（<6 mm）中的颗粒细胞（GC）和卵泡膜细胞（TC）中，UHRF1 mRNA的丰度大于大卵泡（≥8 mm），而在小卵泡GC中则比TC大。在GC和TC中，FGF9治疗增加（P <0.05）UHRF1表示倍数。此外，促黄体生成激素（LH）和胰岛素样生长因子1（IGF1）使TC中UHRF1的表达增加了两倍（P <0.05），而单独或与IGF1组合的福斯高林（腺苷酸环化酶诱导剂）UHRF1则增加了（P <0.05）表示三倍。E2F转录因子抑制剂（E2Fi）在TC中降低了（P <0.05）UHRF1表达，在GC中降低了99％。雌二醇，孕酮和二丁酰-cAMP降低了GC中UHRF1 mRNA的丰度（P <0.05）。仅用FSH治疗GC无效，但与IGF1增强的UHRF1联合使用mRNA丰度提高了2.7倍。白霉素（一种真菌毒素）完全抑制了FSH和IGF1诱导的小卵泡GC中UHRF1的表达。在GC中增加UHRF1 mRNA（即FGF9）的治疗倾向于减少（下降63％；P <0.10）总体DNA甲基化，而在GC中减少UHRF1 mRNA（即E2Fi）的治疗倾向于增加（增加2.4倍；P <0.10）整体DNA甲基化。总体而言，这些结果表明，UHRF1在GC和TC中的表达均受到发育和激素调节，并且UHRF1可能在卵泡生长和发育中起作用，并参与卵巢表观遗传过程。