Abstract
Pregnancy induces respiratory adaptations to meet increased metabolic demands. Despite these adaptations, many pregnant women experience dyspnoea (shortness of breath) and in severe cases, disruptions in the balance of oxygen (O2) and carbon dioxide (CO2) can lead to serious complications. The neuronal and hormonal mechanisms underlying pregnancy-related respiratory adaptations remain poorly understood. Prolactin regulates numerous maternal adaptations and its receptor (Prlr) is expressed by brainstem serotonergic (5-HT) neurons that are known to regulate breathing. We hypothesised that prolactin acts on brainstem 5-HT neurons to drive respiratory changes during pregnancy.
We used a transgenic mouse model to knock out Prlr from 5-HT neurons and respiratory parameters were assessed in prolactin receptor knockout mice (Epet-1CrexPrlrlox/lox, n = 1) and control mice (Prlrlox/lox, n = 2). Respiratory parameters, including inspiratory time (TI), expiratory time (TE), duty cycle, respiratory frequency, respiratory drive, and inspiratory pressure, were continuously monitored via a novel radiotelemetry technique across the oestrous cycle and pregnancy. Sleep-associated breathing events were analysed to minimise physiological variability.
Two distinct sleep-related breathing patterns were identified, suggesting variability in respiratory control mechanisms. Comparing the KO mice (Epet-1CrexPrlrlox/lox, n = 1) to the control mice (Prlrlox/lox, n = 2), we found no differences in respiratory parameters during the oestrous cycle. When comparing dioestrus vs pregnant KO mice (Epet-1CrexPrlrlox/lox, n = 1), respiratory frequency transiently decreased in early gestation, while respiratory drive and inspiratory pressure progressively increased. Similarly, TE was elevated in early pregnancy before stabilising, whereas the duty cycle showed a modest decrease. Compared to dioestrus, KO mice demonstrated consistently higher respiratory frequency but reduced respiratory drive and inspiratory pressure.
While statistical analyses were not conducted due to sample size limitations, preliminary data suggest a role for prolactin in modulating respiratory adaptations via serotonergic pathways. This study was the first to investigate how hormones may regulate respiration during pregnancy by using a novel in vivo technique to measure respiratory parameters.