Reproductive toxicology (Elmsford, N.Y.) · 2025
The role of ATG7-mediated ferroptosis in formaldehyde-induced ovarian injury in rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mao Kun, Yan Hao-Zhe, Yang Jia-Qi, Yin Zi-Xin, Gao Xin-Qi, Liu Hao-Fu, Su Heng, Geng Yuan-Yuan, Ge Pan, Zhou Dang-Xia
Аннотация
BACKGROUND: To investigate the mechanisms of toxicological damage of formaldehyde to the female reproductive system METHODS: A Mendelian randomization method was used to predict a causal relationship between ferroptosis genes and female infertility. Changes in the structure and function of rat ovaries were observed by HE staining and transmission electron microscopy. Combined with molecular experiments, we verified the alterations of GSH, iron ions, MDA levels, and the expression of ferroptosis genes.
RESULTS: Mendelian randomization suggested a significant causal relationship between ATG7 and female infertility. Animal experiments showed that formaldehyde caused abnormal follicular maturation and ovarian mitochondrial alterations. Meanwhile, formaldehyde induced elevated levels of iron ions and MDA and decreased GSH levels. Further detection by Western blotting and qRT-PCR revealed that the expression of the ferroptosis marker gene GPX4 decreased and ATG7 increased in the ovary after formaldehyde stimulation.
CONCLUSIONS: Formaldehyde affected the structure and physiological function of rat ovary by activating the expression level of ATG7 and inhibiting the activity of GPX4, which caused iron overload and elevated levels of peroxides, leading to the occurrence of ferroptosis in ovarian tissue.
RESULTS: Mendelian randomization suggested a significant causal relationship between ATG7 and female infertility. Animal experiments showed that formaldehyde caused abnormal follicular maturation and ovarian mitochondrial alterations. Meanwhile, formaldehyde induced elevated levels of iron ions and MDA and decreased GSH levels. Further detection by Western blotting and qRT-PCR revealed that the expression of the ferroptosis marker gene GPX4 decreased and ATG7 increased in the ovary after formaldehyde stimulation.
CONCLUSIONS: Formaldehyde affected the structure and physiological function of rat ovary by activating the expression level of ATG7 and inhibiting the activity of GPX4, which caused iron overload and elevated levels of peroxides, leading to the occurrence of ferroptosis in ovarian tissue.