Department of Pharmacology, Shenyang Pharmaceutical University, No. 103, Wenhua Rd., Shenhe District, Shenyang 110016, China.
Department of Maternal, Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China.
Int J Mol Sci. 2024 Jul 7;25(13):7451. doi: 10.3390/ijms25137451.
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 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. 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 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 ( < 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 ( < 0.05). Compared with the control group, the Bcl-2 protein expression level in the testes of the DIO-R group significantly decreased ( < 0.05). However, the Bax expression level increased. Thus, the Bcl-2/Bax ratio significantly decreased ( < 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 ( < 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 ( < 0.05). During the in vitro experiment, the late and early apoptotic ratio in the over-expression group increased. 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 -activated apoptosis and spermatogenesis pathway, which may be different from that of DIO.
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（饮食诱导肥胖和饮食诱导肥胖抵抗）小鼠中已经发现了生殖障碍，但它们之间男性生殖功能障碍的机制可能不同。本研究旨在探讨在高脂肪饮食诱导肥胖抵抗（DIO-R）小鼠和 GC-1 spg 细胞中，对精子生成的可能作用和机制，这可能与高脂肪饮食诱导肥胖（DIO）小鼠不同。进行了体内和体外实验。将 小鼠用高脂肪饮食喂养 10 周，建立 DIO 和 DIO-R 小鼠模型。GC-1 spg 细胞用于验证 对精子生成的作用机制。在体内实验中，发现 DIO 和 DIO-R 雄性小鼠的精子生成均受到损害。与对照组相比，DIO 和 DIO-R 雄性小鼠的睾酮、LH、顶体酶（ACE）、透明质酸酶（HAse）和激活转录因子 1（ATF1）活性显著降低（<0.05）。与对照组相比，DIO 组的 B 细胞淋巴瘤-2（Bcl-2）/bcl-2 相关 X 蛋白（Bax）比值显著降低，半胱天冬酶-3 的表达水平显著升高（<0.05）。与对照组相比，DIO-R 组睾丸中 Bcl-2 蛋白表达水平显著降低（<0.05）。然而，Bax 表达水平增加。因此，Bcl-2/Bax 比值显著降低（<0.01）；然而，凋亡相关因子（Fas）、Fas 配体（FasLG）、半胱天冬酶-8、半胱天冬酶-8、半胱天冬酶-3 和半胱天冬酶-3 蛋白表达水平显著增加（<0.05）。与 DIO 组相比，在 DIO-R 小鼠中，ACE、ATF1、Bcl-2 和 Bcl-2/Bax 的生精蛋白表达减少，而促凋亡蛋白表达显著增加（<0.05）。在体外实验中，过表达组的晚期和早期凋亡率增加。过表达增强了凋亡相关蛋白 Fas/FasLG 和 Bax/Bcl-2 的表达，同时抑制了 ATF1 和 GC-1 spg 细胞中与精子相关的蛋白的表达。DIO 和 DIO-R 可损害精子生成。DIO-R 可能通过激活 - 诱导的凋亡和生精途径损害精子生成，这可能与 DIO 不同。
