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

22/09/2026

AI Summary

Pregnancy globally suppresses core temperature circadian and ultradian rhythmicity, reducing thermoregulatory oscillations across timescales.
MPOA estrogen receptor alpha neurons synchronise with Tc in nonpregnant mice; this synchrony is lost during pregnancy and returns after parturition.
Enhanced ERα signalling in MPOA mediates pregnancy lowering of Tc; MPOA ERα manipulation alters maternal rhythms and causes premature birth and offspring mass changes.

TL;DR (AI Generated)

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 a genomic estrogen signaling reporter, we demonstrate that MPOERɑ neurons exhibit enhanced estrogen signaling in late pregnancy.

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.

Basic summary

Proc Natl Acad Sci U S A. 2026 Sep 29;123(39):e2611415123. doi: 10.1073/pnas.2611415123. Epub 2026 Sep 21.

ABSTRACT

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.