Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors

Abstract

Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

Improving pregnancy outcomes in humans through studies in sheep

“…Another emerging application for fetal sheep models in the study of the programming of neurodevelopment is the evaluation of the impact of maternal stress during pregnancy, which is achieved by intermittent and unpredictable maternal isolation in the last trimester (102). Isolation is also used as a stimulus in progeny tests characterizing effects of the maternal environment (e.g., periconceptional undernutrition) on later postnatal HPA axis development in juvenile and adult sheep (182).…”

Correlation of Anxiety and Uterine Artery Doppler Flow in Pregnant Women with High Risk of Down syndrome: A Prospective Cohort Study

“…In a study, anxiety and chronic stress were found to increase serum cortisol and corticotrophin-releasing hormone in both mother and fetus resulting in dysregulations in the hypothalamic-pituitary-adrenal (HPA) axis in the fetus that in part causes structural abnormalities in the hippocampus, frontal cortex, amygdala, and nucleus accumbens (32). Further animal studies have also revealed a signi cant decrease in uterine blood ow due to stress (33)(34)(35). Human studies have also hypothesized a similar effect for stress and anxiety on uterine blood ow (12,17).…”

Analgesia during Parturition in Domestic Animals: Perspectives and Controversies on Its Use

“…Those results were attributed to the deleterious effect of prolonged, sustained myometrial activity on fetal circulation, which significantly decreased gas exchange within the placenta and produced neonatal hypoxia in the fetus. Later studies confirmed that maternal stress produces hyperactivity of the HPA and the sympathetic–adrenal–medullary system, related to catecholamine release, elevated fetal blood pressure, and poor placenta-uterine perfusion [ 41 , 42 ].…”