BACKGROUND Increasing evidence demonstrate that cadmium (Cd) has adverse effects on the mammalian reproductive system. However, the mechanisms underlying the effects of Cd on ovarian function and the strategies to reverse these effects have not been fully elucidated. METHODS In this study, 60 CD-1 mice were divided into four groups (control, melatonin, Cd, Cd with melatonin). During the treatment for 14 days, body weight was measured every 2 days. After the treatment, ovaries were isolated and weighted to observe the morphological and biological characteristics. Statistical analyses were performed using one-way ANOVA followed by Fisher's-multiple range test or chi-squared test, A P value < 0.05 indicated statistical significance. RESULTS We observed that Cd exposure induced ovulatory dysfunction, demonstrated by the reduced number of ovulated oocytes numbers in the Cd group. However, this endoplasmic reticulum (ER) pathway was activated in the Cd-exposed ovaries and the expression of GRP78, ATF4, CHOP, and p-JNK was upregulated, which was reversed by treatment with melatonin. Furthermore, we found that melatonin inhibited Cd-induced activation of cleaved caspase-3, restored the ratio of Bax/Bcl-2, and ultimately decreased the apoptosis of granular cells as detected by TUNEL staining. CONCLUSION Collectively, our findings reveal that melatonin attenuated Cd-induced ovulation dysfunction and cell apoptosis by inhibiting the activation of the ER pathway. Thus, melatonin can be a potential agent to protect mammalian ovaries against Cd toxicity.

中文翻译：

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褪黑素通过抑制内质网应激和细胞凋亡来减轻镉诱导的排卵功能障碍。

背景技术越来越多的证据表明，镉（Cd）对哺乳动物的生殖系统有不利影响。但是，尚未完全阐明Cd对卵巢功能的影响的机制以及逆转这些作用的策略。方法在本研究中，将60只CD-1小鼠分为四组（对照组，褪黑素，Cd，含褪黑素的Cd）。在治疗14天期间，每2天测量一次体重。治疗后，分离卵巢并称重以观察其形态和生物学特征。使用单因素方差分析，然后进行Fisher's多范围检验或卡方检验进行统计学分析，AP值<0.05表示具有统计学意义。结果我们观察到Cd暴露引起排卵功能障碍，Cd组的排卵卵母细胞数目减少证明了这一点。但是，这种内质网（ER）途径在暴露于Cd的卵巢中被激活，GRP78，ATF4，CHOP和p-JNK的表达上调，而褪黑素治疗可逆转该表达。此外，我们发现褪黑素可抑制Cd诱导的裂解的caspase-3活化，恢复Bax / Bcl-2的比率，并最终通过TUNEL染色检测到降低粒状细胞的凋亡。结论总的来说，我们的发现表明褪黑素通过抑制ER通路的激活来减轻Cd诱导的排卵功能障碍和细胞凋亡。因此，褪黑激素可能是保护哺乳动物卵巢免受Cd毒性的潜在药物。此内质网（ER）途径在暴露于Cd的卵巢中被激活，GRP78，ATF4，CHOP和p-JNK的表达上调，而褪黑素治疗可逆转该表达。此外，我们发现褪黑素可以抑制Cd诱导的裂解的caspase-3活化，恢复Bax / Bcl-2的比例，并最终降低颗粒细胞的凋亡，这是通过TUNEL染色检测到的。结论我们的研究结果共同表明，褪黑素通过抑制ER通路的激活来减轻Cd诱导的排卵功能障碍和细胞凋亡。因此，褪黑激素可能是保护哺乳动物卵巢免受Cd毒性的潜在药物。该内质网（ER）途径在暴露于Cd的卵巢中被激活，GRP78，ATF4，CHOP和p-JNK的表达上调，而褪黑素治疗可逆转该表达。此外，我们发现褪黑素可以抑制Cd诱导的裂解的caspase-3活化，恢复Bax / Bcl-2的比例，并最终降低颗粒细胞的凋亡，这是通过TUNEL染色检测到的。结论我们的研究结果共同表明，褪黑素通过抑制ER通路的激活来减轻Cd诱导的排卵功能障碍和细胞凋亡。因此，褪黑激素可能是保护哺乳动物卵巢免受Cd毒性的潜在药物。我们发现褪黑素可抑制Cd诱导的裂解的caspase-3活化，恢复Bax / Bcl-2的比例，并最终通过TUNEL染色检测到降低颗粒细胞的凋亡。结论我们的研究结果共同表明，褪黑素通过抑制ER通路的激活来减轻Cd诱导的排卵功能障碍和细胞凋亡。因此，褪黑激素可能是保护哺乳动物卵巢免受Cd毒性的潜在药物。我们发现褪黑素可抑制Cd诱导的裂解的caspase-3活化，恢复Bax / Bcl-2的比率，并最终通过TUNEL染色检测到降低粒状细胞的凋亡。结论我们的研究结果共同表明，褪黑素通过抑制ER通路的激活来减轻Cd诱导的排卵功能障碍和细胞凋亡。因此，褪黑激素可能是保护哺乳动物卵巢免受Cd毒性的潜在药物。