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.

全世界约有 20 亿人易患碘缺乏症。碘缺乏症主要通过食盐中的碘强化来解决；然而，不加选择地使用碘会增加碘中毒的风险。在本研究中，我们旨在研究过量碘对精子发生产生不利影响的分子机制。Sprague Dawley (SD) 大鼠口服 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。这导致精子数量和运动能力显着下降。分子研究为产生高 SOD 水平的氧化应激、减少 Nrf2、HO-1 和增加 NF-kB 和 Follistatin 提供了证据。进一步的研究表明，抗凋亡（BCL-2，Survivin）的表达减少证明了细胞凋亡增加，促凋亡（Bid、Bax）标志物的表达增加，以及 p53 和其他凋亡调节剂/效应物（细胞色素 c、切割的 PARP、caspase3 和 caspase9）的表达增加。血睾丸屏障蛋白的分析显示紧密连接（JAM-A、Tricellulin）、外质特化（整合素-β1）、粘附连接（N-钙粘蛋白、E-钙粘蛋白、β-连环蛋白）蛋白的表达降低，并且其他连接蛋白编码基因（Claudin1、Claudin 5、Occludin、ZO-1、Testin、Fibronectin、CAR-F）。粘着斑激酶（FAK）和精子发生的关键调节因子（c-Kit受体，雄激素受体）也平行减少。进一步研究显示生殖细胞增殖和分化标志物（PCNA、Cyclin D1、c-Kit、Cdk-4）的表达降低。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丸屏障和细胞骨架而导致精子发生的丧失。