Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Andrologia. 2022 Sep;54(8):e14470. doi: 10.1111/and.14470. Epub 2022 Jun 9.
NOX5 is introduced as a new therapeutic target for infertility treatment. This study aimed to compare the basal and stimulated reactive oxygen species (ROS) production and sperm function in human teratozoospermic (n = 15) and normozoospermic (n = 17) semen samples following calcium overload and NOX5 activation. Washed spermatozoa incubated for 1 h under five various conditions: control group, adding a calcium ionophore A23187, phorbol myristate acetate (PMA), A23187 + PMA, and diphenylene iodonium (DPI) + A23187 + PMA. ROS generation was measured immediately after treatment for 30 min. Motility, viability, acrosome reaction, and apoptosis were evaluated after 1-h incubation. ROS production significantly increased when A23187 or PMA was added to the sperm medium. DPI had suppressive effects on ROS generation. Progressive and total motility significantly decreased following calcium elevation and NOX5 activation, which was somewhat returned by DPI. Necrotic and live cells in teratozoospermia was, respectively, higher and lower than normozoospermia samples. Incubation with A23187 significantly increased the percentage of early and late apoptosis. Teratozoosperm are more vulnerable than normal spermatozoa, and produce more basal and stimulated ROS. It seems that calcium overload induces apoptosis in spermatozoa and loss of viability through MPT pore opening and increased intracellular ROS.
NOX5 被引入作为治疗不育症的新治疗靶点。本研究旨在比较人畸形精子症（n=15）和正常精子症（n=17）精液样本在钙超载和 NOX5 激活后基础和刺激活性氧（ROS）产生和精子功能。将洗涤后的精子在五种不同条件下孵育 1 小时：对照组、加入钙离子载体 A23187、佛波醇 12,13-二酯（PMA）、A23187+PMA 和二苯碘二酮（DPI）+A23187+PMA。处理后立即测量 30 分钟的 ROS 生成。孵育 1 小时后评估运动性、活力、顶体反应和凋亡。当向精子培养基中添加 A23187 或 PMA 时，ROS 生成显著增加。DPI 对 ROS 生成具有抑制作用。钙超载和 NOX5 激活后，前向和总运动性显著下降，DPI 则略有恢复。畸形精子症中的坏死细胞和活细胞分别高于正常精子症样本。用 A23187 孵育显著增加了早期和晚期凋亡的百分比。畸形精子比正常精子更脆弱，产生更多的基础和刺激 ROS。似乎钙超载通过 MPT 孔打开诱导精子凋亡，并通过增加细胞内 ROS 导致活力丧失。
