School of Life Science, Bengbu Medical College, Bengbu, People's Republic of China.
DNA Cell Biol. 2022 Oct;41(10):861-870. doi: 10.1089/dna.2022.0289. Epub 2022 Sep 2.
Varicoceles (VCs) have received widespread attention as a primary factor affecting male fertility and a pathological condition that may lead to decreased sperm count and motility in patients. Many studies have shown that an imbalance of local antioxidant balance exists in patients with VC, leading to an obvious increase in the content of reactive oxygen species (ROS) and may cause reductive stress. Excessive ROS may aggravate spermatogenesis dysfunction and affect male fertility. Poly(ADP-ribose) polymerase (PARP) is an enzyme associated with DNA repair in eukaryotic cells, can be activated by DNA fragments with structural damage, and has been considered a DNA damage receptor in DNA damage repair and apoptosis. We built a rat model of VC and an oxidative damage model of a spermatocyte-derived cell line (GC-2 cells) induced by hydrogen peroxide to study the role of PARP1 in VC. Differentially expressed genes (DEGs) were obtained by RNA sequencing in the testes of VC rats. Analysis of DEGs revealed some genes with significantly altered expression, which were validated in rat and cell models. Immunofluorescence, real-time quantitative PCR analysis, Western blot, and flow cytometry were used to analyze the changes between the control group and the VC or hydrogen peroxide group. Overall, we found that PARP1 protein expression increased in VC rats and in the hydrogen peroxide-induced oxidative stress model of GC-2 cells. Parthanatos may be one of the factors leading to reduced reproductive capacity in VC patients. Our study provides novel insights into the mechanisms of male infertility induced by oxidative stress and provides a new therapeutic target for VC.
精索静脉曲张（VCs）作为影响男性生育力的主要因素之一，受到了广泛关注，也是一种可能导致患者精子数量和活力下降的病理状况。许多研究表明，VC 患者存在局部抗氧化平衡失衡，导致活性氧（ROS）含量明显增加，并可能引起还原应激。过多的 ROS 可能加重生精功能障碍，影响男性生育力。聚（ADP-核糖）聚合酶（PARP）是一种与真核细胞 DNA 修复相关的酶，可被具有结构损伤的 DNA 片段激活，并且被认为是 DNA 损伤修复和细胞凋亡中的 DNA 损伤感受器。我们构建了 VC 大鼠模型和过氧化氢诱导的精原细胞衍生细胞系（GC-2 细胞）氧化损伤模型，以研究 PARP1 在 VC 中的作用。通过 VC 大鼠睾丸的 RNA 测序获得差异表达基因（DEGs）。对 DEGs 的分析揭示了一些表达明显改变的基因，并在大鼠和细胞模型中得到了验证。免疫荧光、实时定量 PCR 分析、Western blot 和流式细胞术用于分析对照组与 VC 或过氧化氢组之间的变化。总的来说，我们发现 PARP1 蛋白表达在 VC 大鼠和过氧化氢诱导的 GC-2 细胞氧化应激模型中增加。Parthanatos 可能是导致 VC 患者生殖能力下降的因素之一。我们的研究为氧化应激诱导的男性不育机制提供了新的见解，并为 VC 提供了新的治疗靶点。
