Cesarean birth elicits long-term effects on vasopressin and oxytocin neurons in the hypothalamic paraventricular nucleus of mice

Birth is an extraordinary event for placental mammals and occurs at a time when key developmental processes are shaping the brain. Remarkably, little is known about the contributions of birth to brain development and whether birth mode (vaginal vs. Cesarean) alters neurodevelopmental trajectories. We previously reported that Cesarean birth reduces vasopressin (VP) neuron number in the hypothalamic paraventricular nucleus (PVN) of mice at weaning. In this study, we investigated whether this effect extends to adulthood and whether birth mode affects oxytocin (OT) neurons, which are another prominent population in the PVN. We found that Cesarean-born adults had fewer VP neurons in the PVN, specifically in magnocellular regions. Interestingly, these regions also had more dying cells following a Cesarean birth, suggesting that cell death may be the underlying mechanism. The PVN of Cesarean-born adults also had smaller VP neuron somas and reduced VP efferent projections. Additionally, Cesarean-born mice showed fewer and smaller OT neurons in the PVN, but these effects were less robust than for VP neurons. We also examined VP and OT neuron number in the supraoptic and suprachiasmatic nuclei but found no effect of birth mode in these regions. Thus, Cesarean birth causes long-term effects on the VP and, to a lesser extent, OT systems in the PVN, suggesting that this region is particularly sensitive to the effects of birth mode. Our findings may help explain the social deficits reported for Cesarean-born mice, and are also of clinical significance given the widespread practice of Cesarean births across the world.