Cesarean section delivery is a risk factor of autism-related behaviors in mice

Masatoshi Nagano,Fumihito Saitow,Hitoshi Ozawa,Yasunori Mikahara,Makoto Uzuki,Shinpei Higo,Toshio Akimoto,Hidenori Suzuki,Katsuhiko Nishimori

doi:10.1038/s41598-021-88437-8

Masatoshi Nagano, Fumihito Saitow + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-88437-8

Copy DOI

Abstract

Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Many meta-analyses have suggested an etiological relationship between C/S delivery and autism spectrum disorders (ASDs). However, as a risk factor for ASDs, C/S delivery has not yet been well studied. Because C/S deliveries have been increasing, it is very important to investigate the causal association between C/S and ASDs. Here, using three approaches, we showed experimentally that C/S delivery induced ASD-like traits in offspring mice, and that some of these changes were ameliorated by one-time oxytocin (OXT) treatment. Treatment with OXT receptor antagonists before natural delivery also induced ASD-related behaviors. Moreover, wild-type mice born to OXT-KO dams showed similar changes. Thus, insufficient OXT exposure from dams to offspring during delivery may be a trigger for ASD-related behaviors.

Highlights

Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy
We first examined the effects of C/S on offspring sociability compared with naturally delivered (ND) mice
The numbers of ultrasonic vocalization (USV) calls emitted by pups separated from their foster dams, ICR mice, were measured at postnatal day (PD) 8

Summary

Introduction

Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Because C/S deliveries have been increasing, it is very important to investigate the causal association between C/S and ASDs. Here, using three approaches, we showed experimentally that C/S delivery induced ASD-like traits in offspring mice, and that some of these changes were ameliorated by one-time oxytocin (OXT) treatment. Treatment with OXT receptor antagonists before natural delivery induced ASD-related behaviors. An etiological relationship between C/S delivery and autism spectrum disorders (ASDs) has been s uggested[2,3] Both the environment and many genes have been recognized as causal factors of A SDs4. We again examined the effects of OXT treatment on the ASD-related behaviors induced in the offspring. We revealed the importance of OXT exposure from dams to pups during delivery for the suppression of ASD-related behaviors in offspring

Methods

Results

Conclusion