INRAE, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France.
Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Krakow, Poland.
Reproduction. 2023 Dec 14;167(1). doi: 10.1530/REP-23-0272. Print 2024 Jan 1.
Adipolin (C1QTNF12) has been described as a regulator of metabolism and is linked with the pathophysiology of PCOS. In this study, for the first time, we show the expression of C1QTNF12 in granulosa cells and its positive effect on porcine granulosa cell proliferation and steroid synthesis.
Adipolin (C1QTNF12) is a recently discovered adipokine that plays an important role in glucose and insulin level regulation. Previous studies showed its reduced level in serum of women suffering from polycystic ovarian syndrome; however, whether C1QTNF12 regulates ovary function is still unknown. The aim of the study was first to determine the level of C1QTNF12 in the porcine ovarian follicles granulosa cells (Gc) and then its in vitro effect on proliferation and steroidogenesis as well as phosphorylation of several signalling pathways. Our results showed that the expression of C1QTNF12 was dependent on follicle size and was higher at the mRNA and protein level in Gc of small than large follicles from both prepubertal and mature animals. Similar pattern was observed for C1QTNF12 concentration in porcine follicular fluid. Additionally, we observed immunolocalisation of C1QTNF12 in Gc, theca cells and oocytes. We found that C1QTNF12 stimulated porcine Gc proliferation via the activation of protein kinase B (AKT). Moreover, C1QTNF12 enhanced progesterone, testosterone and oestradiol secretion by elevating STAR, CYP11A1, HSD3B and CYP19A1 mRNA expression and by activation of MAP3/1 pathway. Additionally, C1QTNF12 increased pMAP3/1-to-MAP3/1 protein expression ratio and enhanced IGF1-induced pTyr-IGF1Rβ-to-IGFR1β and pMAP3/1-to-MAP3/1 protein ratios. Taken together, C1QTNF12 could act directly on proliferation and steroid synthesis and serve as an important factor in in vivo ovarian follicle function, possibly regulating the course of folliculogenesis.
脂肪因子(C1QTNF12)已被描述为代谢的调节剂,与多囊卵巢综合征的病理生理学有关。在这项研究中,我们首次展示了 C1QTNF12 在颗粒细胞中的表达及其对猪颗粒细胞增殖和类固醇合成的积极影响。
脂肪因子(C1QTNF12)是一种新发现的脂肪因子,在调节葡萄糖和胰岛素水平方面发挥着重要作用。先前的研究表明,患有多囊卵巢综合征的女性血清中的 C1QTNF12 水平降低;然而,C1QTNF12 是否调节卵巢功能仍不清楚。本研究的目的首先是确定 C1QTNF12 在猪卵巢卵泡颗粒细胞(Gc)中的水平,然后研究其在体外对增殖和类固醇生成以及几种信号通路磷酸化的影响。我们的结果表明,C1QTNF12 的表达依赖于卵泡大小,并且来自青春期前和成熟动物的小卵泡的 Gc 中,其 mRNA 和蛋白水平均高于大卵泡。在猪卵泡液中也观察到 C1QTNF12 的浓度呈现相似的模式。此外,我们观察到 C1QTNF12 在 Gc、膜细胞和卵母细胞中的免疫定位。我们发现 C1QTNF12 通过激活蛋白激酶 B(AKT)刺激猪 Gc 增殖。此外,C1QTNF12 通过升高 STAR、CYP11A1、HSD3B 和 CYP19A1 mRNA 表达并激活 MAP3/1 通路,增强孕激素、睾酮和雌二醇的分泌。此外,C1QTNF12 增加了 pMAP3/1 至 MAP3/1 蛋白表达的比值,并增强了 IGF1 诱导的 pTyr-IGF1Rβ 至 IGF1Rβ 和 pMAP3/1 至 MAP3/1 蛋白比值。综上所述,C1QTNF12 可以直接作用于增殖和类固醇合成,并作为体内卵巢卵泡功能的重要因素,可能调节卵泡发生过程。