Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring
Tusar Giri,
Susan E. Maloney,
Saswat Giri,
Young Ah Goo,
Jong Hee Song,
Minsoo Son,
Eric Tycksen,
Sara B. Conyers,
Annie Bice,
Xia Ge,
Joel R. Garbow,
James D. Quirk,
Adam Q. Bauer,
Arvind Palanisamy
Affiliations
Tusar Giri
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA
Susan E. Maloney
Department of Psychiatry, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA
Saswat Giri
Graduate Student, School of Public Health and Social Justice, St. Louis University, St. Louis, MO, USA
Young Ah Goo
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
Jong Hee Song
Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
Minsoo Son
Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
Eric Tycksen
Genome Technology Access Center (GTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
Sara B. Conyers
Department of Psychiatry, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA
Annie Bice
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Xia Ge
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Joel R. Garbow
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
James D. Quirk
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Adam Q. Bauer
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Arvind Palanisamy
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA; Corresponding author
Summary: 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.
