The neonatal ketone body is important for primordial follicle pool formation and regulates ovarian ageing in mice  

作　　者：Xin-Ying Wang Xin-Ge Zhang Yong-Juan Sang Dan-Yang Chong Xiao-Qiang Sheng Hai-Quan Wang Chao-Fan Yang GuiJun Yan Hai-Xiang Sun Chao-Jun Li 

机构地区：[1]State Key Laboratory of Reproductive Medicine and China International Joint Research Center on Environment and Human Health,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China [2]Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing University,Nanjing,Jiangsu 210093,China [3]Ministry of Education Key Laboratory of Model Animal for Disease Study,Model Animal Research Center of Nanjing University,Nanjing,Jiangsu 210093,China

出　　处：《Life Metabolism》2022年第2期149-160,共12页生命（代谢（英文）

基　　金：supported by the National Key Research and Development Program of China(2018YFC1004703).

摘　　要：Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood;however,the underlying mechanism is still unclear.Herein,we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing.We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(Hmgcs2)was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum.Reactive oxygen species(ROS)elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles,while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing(POA),which might be related to the activation of cellular endogenous antioxidant system.All these defects could be rescued by ketone body administration,which suppressed ROS-activated follicle apoptosis.Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.

关 键 词：ketone body primordial follicle pool Hmgcs2 ROS POA 

分 类 号：R339.22[医药卫生—人体生理学]