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

Pregnancy induces widespread physiological adaptations, including changes to core temperature (T c ), 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 (MPO ERɑ ). Using in vivo calcium recordings of MPO ERɑ neurons, we show that MPO ERɑ neural activity is synchronized with T c oscillations in nonpregnant mice. Notably, this synchronization is lost during pregnancy and reemerges after parturition, indicating that MPO ERɑ activity and T c are synchronized in a manner that is dependent on reproductive state. Using chemogenetic inhibition, we show that MPO ERɑ neurons are required for the lowering of T c in late pregnancy. Using a genomic estrogen signaling reporter, we demonstrate that MPO ERɑ neurons exhibit enhanced estrogen signaling in late pregnancy. This estrogen signaling helps coordinate maternal T c changes, as selectively ablating ERα expression in the MPO increased T c and its circadian and ultradian rhythmicity. Finally, we show that manipulating MPO ERɑ cell activity and MPO Esr1 expression affected neonates: Silencing MPO ERɑ 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 T c circadian and ultradian rhythmicity during pregnancy and identify ERα as a central modulator of these rhythms with consequences for fetal development.