Hornos Carneiro Maria Fernanda, Shin Nara, Karthikraj Rajendiran, Barbosa Fernando, Kannan Kurunthachalam, Colaiácovo Monica P
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, 14040-903, Brazil.
Genetics. 2020 Feb;214(2):381-395. doi: 10.1534/genetics.119.302939. Epub 2019 Dec 18.
Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals, and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.
内分泌干扰化学物质在我们的环境中普遍存在,但它们对人类生殖健康产生不利影响的机制以及规避其影响的策略在很大程度上仍不为人知。在此,我们表明,补充抗氧化剂辅酶Q10(CoQ10)可挽救由广泛使用的增塑剂和内分泌干扰物双酚A(BPA)诱导的生殖毒性,部分原因是中和氧化应激导致的DNA损伤。CoQ10可显著降低BPA诱导的生殖细胞凋亡、磷酸化检查点激酶1(CHK-1)、双链断裂(DSB)水平升高以及减数分裂终变期卵母细胞中的染色体缺陷。CoQ10可抵消BPA诱导的氧化应激、线粒体功能障碍以及生殖系中抗氧化酶基因表达的增加。最后,CoQ10处理还降低了非整倍体胚胎的水平以及在早期胚胎分裂中观察到的BPA诱导的缺陷。我们提出,CoQ10可能通过清除活性氧和自由基来抵消BPA诱导的生殖毒性,并且这种天然抗氧化剂可能构成一种低风险、低成本的策略,以减轻BPA对生育能力的影响。