Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain

Abstract

Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

Parturition and the perinatal period: can mode of delivery impact on the future health of the neonate?

“…; Boksa et al . ) suggesting that maternal oxytocin administration may have multiple acute effects on central nervous system metabolic responses to anoxia at birth involving oxidative stress and inflammation which can affect the molecular epigenetic machinery.…”

Oxytocin Receptor Signaling in Vascular Function and Stroke

“…In cases of birth-related ischemic injury, OXT administration improved viability of immature hippocampal cells and reduced markers of oxidative stress (Tyzio et al, 2006;Ceanga et al, 2010;Kaneko et al, 2016), which may be linked to associated changes in GABAergic chlorine channels in addition to possible hemodynamic alterations (Tyzio et al, 2006;Kaneko et al, 2016). By contrast, other studies have found that OXT administered to dams of pups undergoing birth-related ischemic injury might actually exacerbate injury due to a vasodilatory reaction leading to exacerbated birth anoxia (Boksa et al, 2015). Critically, an ischemic environment might switch the vasodilatory effect of OXT to a vasoconstrictive one based on studies of isolated cerebral arterioles (Bari et al, 1997).…”

Pregnancy as a valuable period for preventing hypoxia‐ischemia brain damage

“…Oxytocin is the most common agent used to promote effective uterine contraction, especially in primiparous women with prolonged labor, having effects also on CNS maturation in the fetus. Despite clinical evidence showing that oxytocin could affect neonatal brain response to hypoxia, there is just one experimental study (Boksa et al, 2015) using a rat model of global anoxia during birth. Pregnant Sprague‐Dawley received oxytocin infusion twice just prior to the cesarean section and pups were further submitted to anoxic environment for 6 or 15 min.…”

“…However, the exact mechanisms that might explain such differences were not investigated, since all biochemical analysis were performed only in males (Marcelino et al, 2016). In a similar way, oxytocin administration increased lactate levels in a sex-specific manner, but the functional significance of such differences were not discussed in the study (Boksa et al, 2015). However, if the molecular mechanisms of injury are different between sexes, it clearly points that therapeutic approaches should be different for males and females (Charriaut-Marlangue et al, 2018).…”