School of Life Sciences, Royal Global University, Betkuchi, Guwahati, Assam -781035, India; Department of Molecular & Human Genetics, Banaras Hindu University, Uttar Pradesh -221005, India.
Department of Molecular & Human Genetics, Banaras Hindu University, Uttar Pradesh -221005, India.
Reprod Toxicol. 2020 Sep;96:128-140. doi: 10.1016/j.reprotox.2020.06.012. Epub 2020 Jun 25.
Approximately 2 billion people worldwide are susceptible to iodine deficiency. Iodine deficiency has largely been tackled by iodine fortification in salt; however indiscriminate use of iodine raises the risk of iodine toxicity. In this study, we aimed to investigate the molecular mechanisms underlying adverse effect of excess iodine on spermatogenesis. Sprague Dawley (SD) rats were orally administered with 0.7 mg potassium iodide (KI)/100 g Bw and 3.5 mg potassium iodide (KI)/100 g Bw for a period of 60 days. This resulted in significant loss of sperm count and motility. Molecular investigations provided evidence for the generation of oxidative stress with high SOD levels, reduced Nrf2, HO-1 and increased NF-kB and Follistatin. Further investigations showed increased apoptosis evidenced by reduced expression of anti-apoptotic (BCL-2, Survivin), increased expression of pro-apoptotic (Bid, Bax) markers, and increased expression of p53 and other modulators/effectors of apoptosis (cytochrome c, cleaved PARP, caspase3 and caspase9). Analysis of the blood testis barrier proteins showed reduced expression of tight junction (JAM-A, Tricellulin), ectoplasmic specialization (Integrin- β1), adherens junction (N-Cadherin, E-cadherin, β-catenin) proteins, and reduced expression of other junction protein coding genes (Claudin1, Claudin 5, Occludin, ZO-1, Testin, Fibronectin, CAR-F). Focal adhesion kinase (FAK) and key regulators of spermatogenesis (c-Kit receptor, androgen receptor) were also parallelly decreased. Further investigation showed reduced expression of germ cell proliferation and differentiation markers (PCNA, Cyclin D1, c-Kit, Cdk-4). These findings collectively explain the loss of spermatogenesis under excess iodine conditions. In conclusion, excess iodine causes loss of spermatogenesis by inducing oxidative stress and disrupting the blood testis barrier and cytoskeleton.
全世界大约有 20 亿人易患碘缺乏症。碘缺乏症在很大程度上可以通过食盐加碘来解决；然而，碘的无差别使用会增加碘中毒的风险。在这项研究中，我们旨在研究过量碘对精子发生产生不良影响的分子机制。将 Sprague Dawley（SD）大鼠经口给予 0.7 mg 碘化钾（KI）/100 g BW 和 3.5 mg 碘化钾（KI）/100 g BW，持续 60 天。这导致精子计数和活力显著下降。分子研究提供了证据表明氧化应激的产生与高 SOD 水平、Nrf2、HO-1 减少以及 NF-kB 和 Follistatin 增加有关。进一步的研究表明，凋亡增加，表现为抗凋亡（BCL-2、Survivin）标志物表达减少，促凋亡（Bid、Bax）标志物表达增加，以及 p53 和其他凋亡调节剂/效应物（细胞色素 c、裂解 PARP、caspase3 和 caspase9）表达增加。对血睾屏障蛋白的分析表明，紧密连接（JAM-A、Tricellulin）、外质特化（整合素-β1）、黏附连接（N-钙黏蛋白、E-钙黏蛋白、β-连环蛋白）蛋白表达减少，以及其他连接蛋白编码基因（Claudin1、Claudin 5、Occludin、ZO-1、Testin、纤维连接蛋白、CAR-F）表达减少。粘着斑激酶（FAK）和精子发生的关键调节剂（c-Kit 受体、雄激素受体）也平行减少。进一步的研究表明，生殖细胞增殖和分化标志物（PCNA、Cyclin D1、c-Kit、Cdk-4）的表达减少。这些发现共同解释了过量碘条件下精子发生的丧失。总之，过量的碘通过诱导氧化应激和破坏血睾屏障和细胞骨架导致精子发生丧失。
