Maternal sleep deprivation during pregnancy induced offspring germ cells loss through ferroptosis

Primordial follicles form the non-renewable germline reserve in female mammals; their limited number is a key determinant of reproductive lifespan and is crucial for female fertility. Insufficient or parasomnia sleep is common in females, yet little attention is paid to the impact of such sleep disorders during pregnancy on the health of offspring, particularly with regard to ovarian development. In this study, a sleep deprivation (SD) model was established with pregnant mice from 6.5 to 13.5 days of pregnancy. The pregnant mice were subjected to 18 h of SD per day, and the effects on the reproductive function of female offspring and the potential mechanisms were explored. Results showed that SD not only affected maternal weight gain and hormone levels, but also significantly decreased the number of germ cells in female offspring. Furthermore, maternal SD may impact the development of female germ cells by interfering with meiotic progression and inhibiting primordial follicle formation. Importantly, in vitro and in vivo experiments demonstrated that inhibition of ferroptosis improved germ cell loss in offspring caused by maternal SD. Thus, for the first time, our study verified a potential link between germ cell loss during primordial follicle formation and ferroptosis; in theory, this may provide treatment options for reproductive damage in offspring caused by maternal sleep disorders during pregnancy.