Overcoming neonatal sickness: Sex-specific effects of sickness on physiology and social behavior

Abstract

Early-life environmental stressors, including sickness, have the potential to disrupt development in ways that could severely impact fitness. Despite what is known about the effects of sickness on reproduction, the precise physiological mechanisms have not yet been determined. The goal of this study was to investigate the effects of a neonatal immune challenge on adult reproductive physiology and opposite-sex social behavior. Male and female Siberian hamster (Phodopus sungorus) pups were administered lipopolysaccharide ([LPS]; a cell wall component of gram-negative bacteria) or saline injections on postnatal days 3 and 5 and body mass, food intake, and measures of reproductive maturity were taken throughout development. In adulthood, hamsters were placed in staged mating pairs with reproductively mature individuals of the opposite sex, during which a series of behaviors were scored. We found that although males and females showed no change in food intake, body mass, or reproductive behaviors, LPS-treated females had abnormal estrous cycles and smaller ovaries. Females also showed increased investigation of and increased aggression towards males in a reproductive context. In contrast, LPS-treated males showed no change in any physiological measures, nor did they show any changes in behavior. The present findings demonstrate that females may be more robustly affected by neonatal sickness than males and that these effects could have potential impacts on reproductive success. Collectively, the results of this study can be used to expand upon what is already known about sickness and reproduction, specifically the importance of social behaviors involved in pre-copulation and information necessary to choose the appropriate mate.

Early-life sickness may predispose Siberian hamsters to behavioral changes following alterations of the gut microbiome in adulthood

“…Specifically, in order to test the hypothesis that early-life activation of the immune system has long-term consequences on how the gut microbiome and behavior respond to antibiotic treatment in adulthood, we mimicked an early-life infection by injecting pups with LPS and subsequently, exposing those same animals to antibiotic treatment in adulthood to target the microbiome directly. In our previous work, we have shown that early-life LPS did not influence same-sex social behavior in either sex, though we found that LPS-treated females exhibited more aggression with and investigation of male conspecifics in a reproductive context compared to saline controls (Sylvia et al, 2018; Sylvia and Demas, 2017). Here, we hypothesized that individuals treated with exogenous LPS in early life would exhibit more robust physiological and behavioral changes following adult antibiotic treatment.…”

“…These molecules can then act on the brain to initiate the acute-phase response (APR), including fever, lethargy, decreased food intake, and enhanced pain response (Harvey and Boksa, 2012; Perry, 2004; Quan and Banks, 2007). Previous research in our lab has shown that early-life LPS influences investigation and aggression and affects reproductive physiology in females, but not in males (Sylvia and Demas, 2017).…”

Microglial Activation in the Ventral Hippocampus Induced by Acute Social Defeat is Associated with Amygdala Activity

“…LPS injection through peritonea induced the activation of microglia accompanied with sickness behavior, which suggested that the peripheral inflammation connected the brain response [53]. In the present study, at early stages after aggression, plasma GC increased.…”

Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling

“…Corticosterone levels were also elevated in neonatal LPStreated females across developmental timepoints (Sominsky et al, 2012). LPS-treated female Siberian hamsters have abnormal estrous cycles and smaller ovaries relative to saline controls, while male testes mass is not affected (Sylvia & Demas, 2017).…”

“…For example, neonatal LPS decreases social interaction time in female rats tested during adolescence (Doenni et al, 2016;MacRae et al, 2015). In Siberian hamsters, PND3 LPS-treated females investigate an opposite-sex conspecific more and spend more time in attack bouts than saline-treated females (Sylvia & Demas, 2017). LPS administration at later developmental timepoints also influences female social behaviors.…”