男性生殖功能障碍是一种临床疾病，大量病例为特发性。在肥胖（饮食引起的肥胖和饮食引起的抗肥胖）小鼠中发现了生殖障碍，但它们之间的雄性生殖功能障碍背后的机制可能不同。本研究的目的是探讨 miR-34c 对高脂饮食诱导的肥胖抵抗（DIO-R）小鼠和 GC-1 spg 细胞精子产生的可能作用和机制，这可能与高脂饮食诱导的肥胖（DIO）小鼠。进行了体内和体外实验。 C57BL/6J小鼠高脂饮食喂养10周，建立DIO和DIO-R小鼠模型。使用GC-1 spg细胞验证miR-34c对精子产生的机制。在体内实验中，DIO 和 DIO-R 雄性小鼠的精子生成均受到损害。与对照小鼠相比，DIO 和 DIO-R 雄性小鼠的睾酮、LH、顶体酶 (ACE)、HAse 和激活转录因子 1 (ATF1) 活性显着降低 (p < 0.05)。与对照组相比，DIO组B细胞淋巴瘤-2（Bcl-2）/bcl-2相关X蛋白（Bax）比值显着降低，cleaved caspase-3表达水平显着降低。增加（p < 0.05）。与对照组相比，DIO-R组睾丸中Bcl-2蛋白表达水平显着降低（p < 0.05）。然而，Bax 表达水平增加。因此，Bcl-2/Bax 比率显着下降 (p < 0.01)；然而，因子相关凋亡 (Fas)、Fas 配体 (FasLG)、cleaved caspase-8、caspase-8、cleaved caspase-3 和 caspase-3 蛋白表达水平显着增加 (p < 0.05)。与DIO组相比，DIO-R小鼠中ACE、ATF1、Bcl-2和Bcl-2/Bax生精蛋白表达活性降低，而促凋亡蛋白表达显着升高（p < 0.05）。体外实验中，miR-34c过表达组晚期和早期凋亡比例增加。 MiR-34c过表达增强GC-1 spg细胞中凋亡相关蛋白Fas/FasLG和Bax/Bcl-2的表达，同时抑制ATF1和精子相关蛋白的表达。 DIO 和 DIO-R 可能会损害精子的产生。 DIO-R 可通过诱导 miR-34c 激活的细胞凋亡和精子发生途径来损害精子生成，这可能与 DIO 不同。

Male reproductive dysfunction is a clinical disease, with a large number of cases being idiopathic. Reproductive disorders have been found in obese (diet-induced obesity and diet-induced obesity-resistant) mice, but the mechanism behind the male reproductive dysfunction between them may be different. The purpose of this study was to explore the possible role and mechanism of miR-34c on sperm production in high-fat-diet-induced obesity-resistant (DIO-R) mice and GC-1 spg cells, which may differ from those in high-fat-diet-induced obesity (DIO) mice. In vivo and in vitro experiments were performed. C57BL/6J mice were fed a high-fat diet for 10 weeks to establish the DIO and DIO-R mouse model. GC-1 spg cells were used to verify the mechanism of miR-34c on sperm production. During in vivo experiments, sperm production damage was found in both DIO and DIO-R male mice. Compared to the control mice, significantly decreased levels of testosterone, LH, activities of acrosome enzyme (ACE), HAse, and activating transcription factor 1 (ATF1) were found in both DIO and DIO-R male mice (p < 0.05). Compared with the control group, the ratio of B-cell lymphoma-2 (Bcl-2)/bcl-2-associated X protein (Bax) in the DIO group was significantly decreased, and the expression level of cleaved caspase-3 was significantly increased (p < 0.05). Compared with the control group, the Bcl-2 protein expression level in the testes of the DIO-R group significantly decreased (p < 0.05). However, the Bax expression level increased. Thus, the Bcl-2/Bax ratio significantly decreased (p < 0.01); however, the factor-related apoptosis (Fas), Fas ligand (FasLG), cleaved caspase-8, caspase-8, cleaved caspase-3, and caspase-3 protein expression levels significantly increased (p < 0.05). Compared with the DIO group, in DIO-R mice, the activities of ACE, ATF1, Bcl-2, and Bcl-2/Bax's spermatogenesis protein expression decreased, while the apoptosis-promoting protein expression significantly increased (p < 0.05). During the in vitro experiment, the late and early apoptotic ratio in the miR-34c over-expression group increased. MiR-34c over-expression enhanced the expression of apoptosis-related proteins Fas/FasLG and Bax/Bcl-2 while inhibiting the expression of ATF1 and the sperm-associated protein in GC-1 spg cells. DIO and DIO-R could harm sperm production. DIO-R could impair sperm production by inducing the miR-34c-activated apoptosis and spermatogenesis pathway, which may be different from that of DIO.