Oral Presentation ESA-SRB-APEG-NZSE 2022

Prolactin modulation of thermoregulatory circuits provides resilience to thermal challenge of pregnancy and lactation (#223)

Sharon R Ladyman 1
  1. University of Otago, Dunedin, New Zealand

Pregnancy and lactation represent significant challenges to thermal homeostasis due to the progressive generation of metabolic heat from fetal growth and development and then milk production. Since increases in body temperature can be teratogenic and hence detrimental to fetal development, this rising body temperature must be offset by counter-regulatory mechanisms in the mother to prevent hyperthermia. Active adaptation of maternal thermoregulation is most apparent by the decrease in body temperature observed in the last trimester of pregnancy in many species including humans, cows, and rodents, despite peak metabolic heat production from fetal development at this time. Our aim was to investigate the role of the pregnancy hormone prolactin in driving these maternal adaptations in body temperature regulation. First, using chemogenetic and immunohistochemical approaches we demonstrate that within the preoptic area of the hypothalamus (POA) warm-sensitive neurons (WSN), which detect elevations in body temperature and engage downstream effector pathways to lower body temperature, express prolactin receptors (Prlr). While acute prolactin administration did not influence body temperature in virgin male or female mice, the same treatment in lactating mice significantly lowered body temperature, suggesting in certain conditions prolactin action can influence thermoregulation. Deletion of Prlr from the POA lead to significantly elevated body temperature during pregnancy, but not in the pre-pregnancy state, suggesting that prolactin action on WSNs is important for maintaining appropriate body temperature specifically during pregnancy. Finally, while control mice could cope with pregnancy under a mild thermal challenge (30°C), mice lacking Prlr in glutamatergic neurons, which includes many WSNs, had poor pregnancy indicating that prolactin action in glutamatergic neurons provides resilience to thermal challenges during pregnancy. This work highlights a key role for prolactin to regulate the thermoregulatory circuits and provide optimal conditions for successful pregnancies.