Pregnancy damps thermoregulatory rhythms across timescales through neural estrogen signaling in mice.

Pregnancy induces widespread physiological adaptations, including changes to core temperature (Tc), that may reduce fetal heat stress and enhance metabolic stability. Despite the potential importance of maternal thermoregulatory changes, the neural mechanisms organizing homeostatic rhythms during pregnancy remain poorly understood. Here, we demonstrate that pregnancy profoundly reshapes thermoregulatory dynamics across diurnal and ultradian timescales and that these changes are partially orchestrated by estrogen receptor alpha (ERα) signaling in neurons of the medial preoptic area (MPOERɑ). Using in vivo calcium recordings of MPOERɑ neurons, we show that MPOERɑ neural activity is synchronized with Tc oscillations in nonpregnant mice. Notably, this synchronization is lost during pregnancy and reemerges after parturition, indicating that MPOERɑ activity and Tc are synchronized in a manner that is dependent on reproductive state. Using chemogenetic inhibition, we show that MPOERɑ neurons are required for the lowering of Tc in late pregnancy. Using a genomic estrogen signaling reporter, we demonstrate that MPOERɑ neurons exhibit enhanced estrogen signaling in late pregnancy. This estrogen signaling helps coordinate maternal Tc changes, as selectively ablating ERα expression in the MPO increased Tc and its circadian and ultradian rhythmicity. Finally, we show that manipulating MPOERɑ cell activity and MPO Esr1 expression affected neonates: Silencing MPOERɑ neurons led to premature birth, while both silencing and gene ablation led to sex-specific changes to offspring body mass. In summary, these findings reveal a global suppression of Tc circadian and ultradian rhythmicity during pregnancy and identify ERα as a central modulator of these rhythms with consequences for fetal development.