Abstract：
The corpus luteum (CL) is a temporary endocrine gland that synthesizes progesterone. The luteal progesterone plays a central role in the regulation of the estrous cycle as well as the implantation and maintenance of pregnancy. Our previous study showed the expression of adropin and its receptor, GPR19, in the luteal cells and its significant role in luteinization. The aim of the present study was to investigate the in vitro effect of adropin on hCG-induced ovarian functions in adult mice. We also evaluated the effect of exogenous treatment with adropin on ovarian steroidogenesis and anti-oxidant parameters, with special emphasis on CL function. Our results demonstrated that adropin acts synergistically with hCG to promote ovarian steroidogenesis and survival by increasing the expression of StAR, 3β-HSD, and aromatase proteins and decreasing the BAX/BCL2 ratio. Exogenous adropin treatment increased progesterone production by increasing the expression of GPR19, StAR and 3β-HSD enzymes in the mouse ovary. Also, adropin inhibited the luteal oxidative stress by increasing nuclear translocation of NRF-2 in CL, which resulted in increased HO-1 expression and SOD, catalase activity. Decreased oxidative stress might inhibit the translocation of NF-κB into the nucleus of luteal cells, resulting into increased survival and decreased apoptosis, as evident by decreased lipid peroxidation, BAX/BCL2 ratio, caspase 3, active caspase 3 expression, and TUNEL-positive cells in adropin treated mice. Our findings suggest that adropin can be a promising candidate that can enhance the survivability of the CL.
摘要：
黄体（CL）是合成孕酮的临时内分泌腺。黄体孕酮在调节发情周期以及植入和维持妊娠中起着核心作用。我们之前的研究显示了adropin及其受体的表达，GPR19，在黄体细胞中及其在黄体化中的显著感化。本研究的目的是研究adropin对成年小鼠hCG诱导的卵巢功能的体外影响。我们还评估了adropin外源性治疗对卵巢类固醇生成和抗氧化参数的影响，特别强调CL功能。我们的结果表明，adropin与hCG协同作用，通过增加StAR的表达来促进卵巢类固醇生成和存活。3β-HSD,和芳香化酶蛋白并降低BAX/BCL2比率。外源性adropin处理通过增加小鼠卵巢中StAR和3β-HSD酶的表达来增加孕酮的产生。此外，adropin,通过GPR19，通过增加CL中NRF-2的核易位来抑制黄体氧化应激，导致HO-1表达和SOD增加，过氧化氢酶活性。氧化应激降低可能抑制NF-κB向黄细胞核的转位,导致存活率增加和细胞凋亡减少，脂质过氧化作用减少，BAX/BCL2比值，caspase3，活性caspase3表达，和adropin处理的小鼠中的TUNEL阳性细胞。我们的研究结果表明，adropin可能是一种有希望的候选药物，可以延长CL的寿命，并可能作为治疗黄体功能不全的潜在治疗选择。
