Targeting the Stress System During Gestation: Is Early Handling a Protective Strategy for the Offspring?

Valentina Castelli,Anna Brancato,Gianluca Lavanco,Fulvio Plescia

doi:10.3389/fnbeh.2020.00009

Abstract

The perinatal window is a critical developmental time when abnormal gestational stimuli may alter the development of the stress system that, in turn, influences behavioral and physiological responses in the newborns. Individual differences in stress reactivity are also determined by variations in maternal care, resulting from environmental manipulations. Despite glucocorticoids are the primary programming factor for the offspring’s stress response, therapeutic corticosteroids are commonly used during late gestation to prevent preterm negative outcomes, exposing the offspring to potentially aberrant stress reactivity later in life. Thus, in this study, we investigated the consequences of one daily s.c. injection of corticosterone (25 mg/kg), from gestational day (GD) 14–16, and its interaction with offspring early handling, consisting in a brief 15-min maternal separation until weaning, on: (i) maternal behavior; and (ii) behavioral reactivity, emotional state and depressive-like behavior in the adolescent offspring. Corticosterone plasma levels, under non-shock- and shock-induced conditions, were also assessed. Our results show that gestational exposure to corticosterone was associated with diminished maternal care, impaired behavioral reactivity, increased emotional state and depressive-like behavior in the offspring, associated with an aberrant corticosterone response. The early handling procedure, which resulted in increased maternal care, was able to counteract the detrimental effects induced by gestational corticosterone exposure both in the behavioral- and neurochemical parameters examined. These findings highlight the potentially detrimental consequences of targeting the stress system during pregnancy as a vulnerability factor for the occurrence of emotional and affective distress in the adolescent offspring. Maternal extra-care proves to be a protective strategy that confers resiliency and restores homeostasis.

Highlights

As mediators of the stress response, glucocorticoids are among the main primary programming factors conveying maternal stress to the fetus via the placenta (Zarrow et al, 1970; Schmidt et al, 2019), through the activation of the glucocorticoid receptors (GR), whose ontogenetic pattern has been detected in human from the early prenatal life stages (Kitraki et al, 1997; Diaz et al, 1998; Kemp et al, 2016)
Rats’ body weight was recorded from postnatal day (PND) 2 to PND 21 in order to obtain data related to the influence of a single daily corticosterone administration and early handling procedure on weight gain during the pre-weaning period
No significant differences in number, weight, morbidity or mortality were observed among the different experimental groups

Summary

Introduction

Numerous studies across a wide range of species have shown that prenatal exposure to different conditions such as infections, nutritional deficiencies, teratogenic substances, and emotional distress, predisposes the newborns to a spectrum of different disorders characterized by deficits in cognitive functioning, motor, and visuospatial abilities and to the genesis of chronic systemic diseases (Cannizzaro et al, 2002, 2005, 2006b, 2007, 2008; Hellemans et al, 2010; Leggio et al, 2014; Sarro et al, 2014; Martines et al, 2016; Moukarzel et al, 2018). Exposure to glucocorticoids during pregnancy, reducing negative-feedback on HPA axis, increases cortisol release in the progeny (Alexander et al, 2012): this leads to a slower recovery from stressors, reducing coping strategy in aversive situations (Welberg et al, 2001; Plescia et al, 2013). This evidence represents a key issue in the therapeutic administration of antenatal corticosteroids, which are commonly used when at risk of preterm delivery to ensure the survival of the preterm infant (Singh et al, 2012). Treating pregnant rodents with synthetic glucocorticoids leads to offspring with similar HPA axis- and behavioral changes as prenatally stressed offspring (Schmidt et al, 2019)

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