Castiglione Roberto, Vivacqua Adele, Santoro Marta, De Rose Daniela, Peluso Giuseppina, Panza Salvatore, Aquila Saveria, D'Agata Rosario
Department of Experimental and Clinical Medicine, University of Catania, 95123 Catania, Italy.
Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.
J Clin Med. 2023 Jun 4;12(11):3844. doi: 10.3390/jcm12113844.
Recent evidence suggests that the male gonad is a potential target of glucagon-like peptide-1 (GLP-1). We investigated the effects of glucagon-like peptide-1 (GLP-1) on sperm function and the molecular mechanisms through which it may act. Semen samples of healthy men were incubated in the presence or absence of a GLP-1 mimetic analog, exendin-4 (Exe). In a different analysis, sperm were exposed to tumor necrosis factor (TNF-α) alone and, in some tubes, TNF-α was added after previous exposure to exendin-4 (Exe). Sperm parameters and protein-kinase B (p-Akt), insulin receptor substrate-1 (p-IRS-1 Ser312), and c Jun N-terminal protein kinase (p-JNK Thr183/Tyr185) were considered and evaluated. Sperm parameters, when incubated for 4 h in a simple defined balanced salt solution lacking protein, declined progressively with incubation time. The maximum decline was associated with a significant decrease in phosphorylated protein kinase B (p-Akt), concomitantly to an increase in insulin receptor substrate-1 (p-IRS-1 Ser312) and c Jun N-terminal protein kinase (p-JNK Thr183/Tyr185). Preincubation with exendin-4 (Exe) prevented this decline and maintained sperm motility (progressive-PM and total-TM). TNF-α exposure resulted in decreased sperm motility (PM and TM) and viability (V) in a concentration-dependent manner. Exe addition attenuated this TNF-α negative effect on sperm parameters. Glucagon-like peptide-1 (GLP-1) also acts by reducing levels of the "negative" kinases p-IRS-1Ser312 and p-JNK. An imbalance involving these three kinases in sperm, as it occurs in somatic cells, is a novel scenario that may participate in sperm physiopathology.
近期证据表明，男性性腺是胰高血糖素样肽-1（GLP-1）的潜在作用靶点。我们研究了胰高血糖素样肽-1（GLP-1）对精子功能的影响及其可能的作用分子机制。将健康男性的精液样本在有或无GLP-1模拟类似物艾塞那肽-4（Exe）的情况下进行孵育。在另一项分析中，精子单独暴露于肿瘤坏死因子（TNF-α），在一些试管中，先将精子暴露于艾塞那肽-4（Exe）后再添加TNF-α。对精子参数以及蛋白激酶B（p-Akt）、胰岛素受体底物-1（p-IRS-1 Ser312）和c-Jun氨基末端蛋白激酶（p-JNK Thr183/Tyr185）进行了评估。在缺乏蛋白质的简单限定平衡盐溶液中孵育4小时后，精子参数随孵育时间逐渐下降。最大降幅与磷酸化蛋白激酶B（p-Akt）的显著降低相关，同时胰岛素受体底物-1（p-IRS-1 Ser312）和c-Jun氨基末端蛋白激酶（p-JNK Thr183/Tyr185）增加。用艾塞那肽-4（Exe）预孵育可防止这种下降并维持精子活力（前向运动-PM和总运动-TM）。TNF-α暴露导致精子活力（PM和TM）和存活率（V）以浓度依赖性方式降低。添加Exe可减轻TNF-α对精子参数的这种负面影响。胰高血糖素样肽-1（GLP-1）还通过降低“负性”激酶p-IRS-1Ser312和p-JNK的水平发挥作用。精子中这三种激酶的失衡，如同在体细胞中发生的情况一样，是一种可能参与精子生理病理学的新情况。
