Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia

Am J Physiol Regul Integr Comp Physiol. 2015 Apr 1;308(7):R659-67. doi: 10.1152/ajpregu.00418.2014. Epub 2015 Feb 4.


Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

Keywords: control of breathing; development; sexual dimorphism; sleep disordered breathing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Animals, Newborn
  • Anxiety, Separation / blood
  • Anxiety, Separation / complications*
  • Anxiety, Separation / physiopathology
  • Body Temperature Regulation*
  • Body Weight
  • Disease Models, Animal
  • Endocrine System / metabolism
  • Endocrine System / physiopathology*
  • Estradiol / blood
  • Female
  • Hypoxia / complications*
  • Hypoxia / physiopathology
  • Lung / physiopathology*
  • Ovariectomy
  • Oxygen Consumption
  • Plethysmography, Whole Body
  • Progesterone / blood
  • Pulmonary Ventilation*
  • Rats, Sprague-Dawley
  • Respiratory Rate
  • Risk Factors
  • Sleep Apnea Syndromes / blood
  • Sleep Apnea Syndromes / etiology
  • Sleep Apnea Syndromes / physiopathology
  • Stress, Psychological / blood
  • Stress, Psychological / complications*
  • Stress, Psychological / physiopathology


  • Progesterone
  • Estradiol