Cadmium (Cd), a toxic heavy metal, is a known endocrine disruptor that is associated with reproductive complications. However, few studies have explored the effects of Cd exposure on features of polycystic ovary syndrome (PCOS) and premature ovary failure (POF). In this study, we assessed whether doses found in workers occupationally exposed to Cd and subacute exposure result in hypothalamic-pituitary-gonadal (HPG) axis and other irregularities. We administered CdCl₂ to female rats (100 ppm in drinking water for 30 days) and then assessed Cd levels in the blood, HPG axis and uterus. Metabolic features, HPG axis function, reproductive tract (RT) morphophysiology, inflammation, oxidative stress (OS), and fibrosis were evaluated. Cd exposure increased Cd levels in the serum, HPG axis, and uterus. Cd rats displayed metabolic impairments, such as a reduction in adiposity, dyslipidemia, and insulin resistance (IR). Cd exposure also caused improper functioning in the HPG. Specifically, Cd exposure caused irregular estrous cyclicity, abnormal hypothalamic gene expression (upregulated – Kiss1, AR and mTOR; downregulated – Kiss1R, LepR and TNF-α), high LH levels, low AMH levels and abnormal ovarian follicular development, coupled with a reduction in ovarian reserve and antral follicle number was observed, suggesting ovarian depletion. Further, Cd exposure caused a reduction in corpora lutea (CL) and granulosa layer thickness together with an increase in cystic/atretic follicles. In addition, Cd exposure caused RT inflammation, OS and fibrosis. Finally, strong positive correlations were observed between serum, RT Cd levels, IR, dyslipidemia and estrous cycle length, cystic, atretic follicles, LH levels, and RT inflammation. Thus, these data suggest that subacute Cd exposure using doses found in workers occupationally exposed to Cd disrupt the HPG axis function, leading to PCOS and POF features and other abnormalities in female rats.

镉（Cd）是一种有毒的重金属，是已知的内分泌干扰物，与生殖并发症有关。但是，很少有研究探讨镉暴露对多囊卵巢综合征（PCOS）和卵巢早衰（POF）特征的影响。在这项研究中，我们评估了在职业性接触Cd和亚急性接触的工人中发现的剂量是否导致下丘脑-垂体-性腺（HPG）轴和其他异常情况。我们使用了CdCl ₂雌性大鼠（饮用水中100 ppm，持续30天），然后评估血液，HPG轴和子宫中的Cd水平。评估了代谢特征，HPG轴功能，生殖道（RT）形态生理学，炎症，氧化应激（OS）和纤维化。镉暴露会增加血清，HPG轴和子宫中的镉含量。镉大鼠表现出代谢障碍，例如肥胖，血脂异常和胰岛素抵抗（IR）降低。镉暴露还导致HPG功能不正常。具体而言，镉暴露会导致不规则的发情周期，下丘脑基因表达异常（上调– Kiss1，AR和mTOR；下调– Kiss1R，LepR和TNF-α），LH水平高，AMH水平低和卵巢卵泡发育异常，并伴有降低卵巢储备和窦泡数 提示卵巢耗竭。此外，镉的暴露导致黄体（CL）和颗粒层厚度的减少以及囊性/闭锁性卵泡的增加。另外，镉暴露会引起RT炎症，OS和纤维化。最后，在血清，RT Cd水平，IR，血脂异常和发情周期长度，囊性，闭锁卵泡，LH水平和RT炎症之间观察到强正相关。因此，这些数据表明，使用职业性接触Cd的工人发现的亚急性Cd暴露剂量会破坏HPG轴功能，导致雌性大鼠出现PCOS和POF功能以及其他异常情况。OS和纤维化。最后，在血清，RT Cd水平，IR，血脂异常和发情周期长度，囊性，闭锁卵泡，LH水平和RT炎症之间观察到强正相关。因此，这些数据表明，使用职业性接触Cd的工人发现的亚急性Cd暴露剂量会破坏HPG轴功能，导致雌性大鼠出现PCOS和POF特征以及其他异常情况。OS和纤维化。最后，在血清，RT Cd水平，IR，血脂异常和发情周期长度，囊性，闭锁卵泡，LH水平和RT炎症之间观察到强正相关。因此，这些数据表明，使用职业性接触Cd的工人发现的亚急性Cd暴露剂量会破坏HPG轴功能，导致雌性大鼠出现PCOS和POF特征以及其他异常情况。