Abstract
During pregnancy, thermoregulation is tightly controlled to protect the foetus from harmful elevated temperatures. Stress-induced hyperthermia is a component of the stress response that increases alertness to a perceived threat. Previous literature has shown that like other aspects of the stress response, stress-induced hyperthermia is attenuated in late pregnancy. We sought to investigate how stress-induced hyperthermia is attenuated in pregnancy of mice. The lactogenic hormones, prolactin and placental lactogen, have been previously shown to act through the prolactin receptor (Prlr) to keep maternal temperature in pregnancy low to ensure successful reproductive outcomes. We hypothesised that Prlr signalling in the brain would attenuate stress-induced hyperthermia during pregnancy. To investigate this, we specifically knocked out Prlr from glutamatergic (Vglut2) neurons in mice (Prlrlox/lox/Vglut2Cre). These neurons have been implicated in maternal adaptations and in stress-induced hyperthermia. Using radiotelemetry to record core temperature (Tcore) and activity levels, non-pregnant and pregnant mice were handled daily by scruffing the skin on the back of the neck to elicit a stress-induced hyperthermic response. In pregnant control mice (Prlrlox/lox), stress-induced hyperthermia became attenuated from day 12 of pregnancy. This was not due to habituation to the stressor, as non-pregnant mice did not show any attenuation of the stress-induced Tcore response following repeated handling for up to 20 days. In the Prlrlox/lox/Vglut2Cre mice, the pregnancy-induced attenuation of stress-induced Tcore was markedly delayed, only appearing at day 14 of pregnancy. The changes were specific to the temperature response to stress, as both genotypes displayed similar levels of stress-induced activity following handling. Together, these data demonstrate that stress-induced hyperthermia is attenuated during pregnancy in mice and that this effect is at least partially mediated by Prlr signalling in glutamate neurons. However, as the stress-induced Tcore response of the knockout mice was eventually attenuated in late pregnancy (gestation day 15-17), comparable to controls, other factors may also be involved.