Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring

• Published in: iScience 2024-02, Vol.27 (2), p.108960-108960, Article 108960
• Main Authors: Giri, Tusar, Maloney, Susan E., Giri, Saswat, Goo, Young Ah, Song, Jong Hee, Son, Minsoo, Tycksen, Eric, Conyers, Sara B., Bice, Annie, Ge, Xia, Garbow, Joel R., Quirk, James D., Bauer, Adam Q., Palanisamy, Arvind
• Format: Article
• Language: English
• Subjects: Behavioral neuroscience; Endocrinology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108960

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies. [Display omitted] •Induced birth with oxytocin did not affect maternal and neonatal wellbeing•Maternally administered oxytocin downregulated oxytocin receptor in the developing brain•Oxytocin exposure at birth altered early life communication in the pups•Oxytocin exposed offspring had sex-specific deficits in empathy and brain connectivity Endocrinology; Neuroscience; Behavioral neuroscience