Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products...Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products,paints,food,and cosmetics.In this study,we found a substantial elevation of Ti in the follicular fluid of females diagnosed with nonhyperandrogenic PCOS(non-HA PCOS).Therefore,we orally subjected female rats to nTiO_(2) at 10 and 100 mg/kg body weight for 10 weeks.We found that nTiO_(2) triggered non-HA PCOS-like symptoms,including the increase of cystic follicles,estrous cycle disorder,and abnormal ovulation,but without high testosterone.By transcriptome sequencing,we identified that nTiO_(2) exposure inhibited the steroid hormone synthesis and activated the proapoptotic pathways.Upon validating these altered pathways,we discovered that aromatase(Cyp19a1)overexpression contributed to the decline in testosterone/estradiol ratio.Mean-while,the apoptosis of granulosa cells was increased by nTiO_(2) exposure,which might result in the disorder of follicular development.This study presents the evidences revealing a pronounced correlation between nTiO_(2) exposure and the emergence of non-HA PCOS,urging people to promote the safe utilization of nTiO_(2).展开更多
基金supported by the National Natural Science Foundation of China(Nos.81871161 and 32301082)Fujian Provincial Health Technology Project for their attribution from(No.2023GGB01)the Natural Science Foundation of Fujian Province(No.2021J01343).
文摘Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products,paints,food,and cosmetics.In this study,we found a substantial elevation of Ti in the follicular fluid of females diagnosed with nonhyperandrogenic PCOS(non-HA PCOS).Therefore,we orally subjected female rats to nTiO_(2) at 10 and 100 mg/kg body weight for 10 weeks.We found that nTiO_(2) triggered non-HA PCOS-like symptoms,including the increase of cystic follicles,estrous cycle disorder,and abnormal ovulation,but without high testosterone.By transcriptome sequencing,we identified that nTiO_(2) exposure inhibited the steroid hormone synthesis and activated the proapoptotic pathways.Upon validating these altered pathways,we discovered that aromatase(Cyp19a1)overexpression contributed to the decline in testosterone/estradiol ratio.Mean-while,the apoptosis of granulosa cells was increased by nTiO_(2) exposure,which might result in the disorder of follicular development.This study presents the evidences revealing a pronounced correlation between nTiO_(2) exposure and the emergence of non-HA PCOS,urging people to promote the safe utilization of nTiO_(2).