Litter size reduction accentuates maternal care and alters behavioral and physiological phenotypes in rat adult offspring

Abstract

Maternal behavior has a substantial impact on the behavioral, endocrine, and neural development of the pups. This study investigated the effect of altering the neonatal nutritional environment by modifying the litter size on maternal care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored daily during lactation (PND2-21). The weight gain, food intake, adiposity, and biochemical landmarks of offspring rats were evaluated. On PND60, performances in the open field, elevated plus-maze (EPM), and fear conditioning test were measured. The reduction of the litter size enhanced maternal care in lactating rats, increasing the arched-back posture and licking pups. SL offspring exhibited accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia, and hyperleptinemia in adulthood. The SL offspring of both sexes showed an increase in the anti-thigmotactic effect in the open field, an intact anxious-phenotype in the EPM, and a decrease in the time spent freezing during the fear-conditioning test, compared to NL. The neonatal environment as determined by litter size plays a crucial role in programming the adult metabolic phenotype as well as behavioral responses to stressful stimuli, with an impact on anxiety-like and fear behaviors. These behavioral changes in offspring may be, at least in part, a result of increased maternal care.

Maternal exposure to high‐fat diet modifies anxiety‐like/depression‐like behaviors and compounds of Serotonergic System in offspring: A preclinical systematic review

“…Two studies, however, found no differences regarding anxiety‐like behavior (Peleg‐Raibstein et al., 2012; Rincel et al., 2016) and Sasaki et al. (2014) found this behavior to be less prevalent in young offspring (Balsevich et al., 2016; Chen et al., 2008; Dong et al., 2013; Enes‐Marques & Giusti‐Paiva, 2018; Fiorotto et al., 1991; Keesey & Hirvonen, 1997; Lawlor et al., 2007; Leung & Lao, 2000; Oken & Gillman, 2003; Orozco‐Solís et al., 2010; Plagemann, 2005; Sasaki et al., 2014; Tozuka et al., 2009). However, another study by the same author using the same amount of energy from fat and the same behavioral test found a higher prevalence of this behavior in animals at 90 days of life (Sasaki et al., 2013).…”

“…The size of the litters also may affect body weight (Fiorotto et al., 1991) and behavior (Enes‐Marques & Giusti‐Paiva, 2018). Small litters are associated with over‐nutrition (Chen et al., 2008; Fiorotto et al., 1991) and large litters with under‐nutrition (Fiorotto et al., 1991).…”

Reducing Pup Litter Size Alters Early Postnatal Calcium Homeostasis and Programs Adverse Adult Cardiovascular and Bone Health in Male Rats

“…This is particularly important, as the quality and quantity of maternal care during lactation can impact on offspring behavioral, endocrine and neural development (see review by Curley and Champagne [61]). Specifically, a recent study demonstrated that dams whose litters were reduced to 3 pups (to induce postnatal overnutrition) have improved maternal care, characterize by increased time devoted to arched nursing and licking pups [62]. Not surprisingly the pups had early accelerated growth and were overweight by PN60, as indicated by increased adiposity, and were hyperglycemic and hyperleptinemic [62].…”

“…Specifically, a recent study demonstrated that dams whose litters were reduced to 3 pups (to induce postnatal overnutrition) have improved maternal care, characterize by increased time devoted to arched nursing and licking pups [62]. Not surprisingly the pups had early accelerated growth and were overweight by PN60, as indicated by increased adiposity, and were hyperglycemic and hyperleptinemic [62]. These findings are however difficult to compare directly to the results of the current study where the Reduced litter pups had decreased postnatal growth, which suggests that the extent of litter size reduction in the current study is unlikely to have resulted in improved maternal care.…”

Differential fate between oxytocin and vasopressin cells in the developing mouse brain

“…However, at gestational day 16, females were singly housed and were daily checked (twice a day) for the presence of pups from the outside of the cages. The day of delivery ∼4 h after birth, designated as postnatal day (P0), newborn pups were weighted and litter size was adjusted to 5–6 pups per litter to normalize offspring access to maternal feeding resources and care ( Enes-Marques and Giusti-Paiva, 2018 ). All animals were left undisturbed, except weekly weight measurements and cage changes until euthanasia.…”