Altered thermal preference by preoptic estrogen receptor alpha neurons in postpartum females

Objective

This study aims to investigate how reproductive experience (RE) alters thermal preference and thermoregulation in female mice, with a focus on estrogen receptor alpha (ERα)-expressing neurons in the preoptic area (POA).

Methods

Thermal preference and body temperature were measured in female mice with and without RE, and virgin female mice with selective deletion of ERα from the POA (ERα^POA-KO). The number and activity of ERα-expressing POA neurons (ERα^POA) were assessed using immunohistochemistry and in vitro electrophysiology in response to temperature changes and ERα agonist.

Results

We showed that female mice prefer a cooler environment starting from late pregnancy and persisting long term postpartum. Female mice with RE (>4 weeks post-weaning) displayed lower body temperature and a lower thermal preferred temperature, and lost preference for warm environments (30 °C) but preserved avoidance of cold environments (15 °C). This was associated with a significant decrease in the number of ERα^POA neurons. Importantly, virgin female ERα^POA-KO mice displayed lower thermal preferred temperature and impaired warm preference, mimicking RE mice. We further found that distinct ERα^POA subpopulations can be regulated by temperature changes with or without presynaptic blockers, and by ERα agonist. More importantly, RE decreased the number of warm-activated ERα^POA neurons and reduced the excitatory effects of warmth and estrogen-ERα signaling, while cold-activated ERα^POA neurons were slightly enhanced in female mice with RE.

Conclusion

Our results support that the thermosensing ability and estrogenic effects in ERα^POA neurons are regulated by reproductive experience, altering thermal preference.