Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Livia H Morais,Ana Paula Ramos Costa,Gerard M Moloney,Sophie Casey,Timothy G Dinan,John F Cryan,Karen A Scott,Anna V Golubeva

doi:10.1038/s41386-021-01040-3

Abstract

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

Highlights

INTRODUCTION Birth delivery byCaesarean-section (C-section), when medically indicated, is a crucial life-saving procedure
There was no significant effect of the mode of delivery, a sustained increase in the hormone concentration was observed in VB and CS mice following highdose OXT administration in early in life (Fig. 1b)
We hypothesised that Oxtr and AVP1a receptor mRNA expression in this region would provide us with evidence of how the exposure to a stressful stimulus at birth might regulate the OXT system

Summary

Introduction

INTRODUCTION Birth delivery byCaesarean-section (C-section), when medically indicated, is a crucial life-saving procedure. In recent decades, the use of elective C-section has dramatically increased worldwide, with rates exceeding World Health Organisation guidelines (of 10–15%), especially in middle- and high-income countries [1]. This trend raises significant concerns given the growing evidence for an association between C-section delivery and increased risk for immune and metabolic disorders [2,3,4,5]. OXT is a key modulator of mammalian maternal-offspring attachment and social behaviour [12,13,14,15,16]. There is a growing interest in the OXT system as a potential target in the treatment of neuropsychiatric disorders associated with stress and social dysfunction [24,25,26,27,28,29]

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Results

Conclusion