Ageing reveals the latent effects of early life stress on respiratory and metabolic function in female rats: Novel insights into the sex-specific origins of sleep apnoea.

Sleep apnoea (SA) is ∼2 times more prevalent in men than women. However, this changes at menopause as the occurrence of SA increases and matches that of men. Menopause is a natural process, but it remains unclear why SA emerges only in a subpopulation of ageing women. Early life stress has persistent and sex-specific effects on the brain. Since loss of ovarian hormones is commonly invoked to explain the emergence of various diseases in menopausal women, we tested the hypothesis that the impacts of early life stress on respiratory control remain latent until they reach old age. Newborn rats were either subjected to neonatal maternal separation (NMS; 3 h/day; postnatal days 3-12) or remained undisturbed (CTRL). Females were then raised under standard conditions until they reached adulthood (12-17 weeks), middle-age (35-40 weeks) or old age (60-65 weeks). Respiratory activity was measured with whole body plethysmography. Body weight and composition was assessed with nuclear magnetic resonance. NMS augmented the apnoea index; however, this effect was detected only in old females. Body mass index and the percentage of body fat increased progressively; these changes were enhanced by NMS and most notable in old females. We conclude that NMS compromises the ageing trajectory of female rats and leads to the development of a phenotype that shares many features reported in SA patients, including respiratory and metabolic dysfunction. Prior life experiences may be an important risk factor in the development of SA in ageing women.