Early-life resource scarcity in mice does not alter adult corticosterone or preovulatory luteinizing hormone surge responses to acute psychosocial stress

Abstract

Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4-11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Further, under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, or proestrous females reared in standard or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often, and their offspring were smaller than standard-reared offspring on PND11, dam corticosterone concentrations were similar on PND11. To test if ALPS disrupts the LH surge by blunting the increase in excitatory GABAergic input to gonadotropin-releasing hormone (GnRH) neurons on the afternoon of proestrus, whole-cell voltage-clamp recordings were conducted. The frequency of GABAergic postsynaptic currents in GnRH neurons was not altered by LBN, ALPS, or their interaction. It remains possible that ALPS acts at afferents of GnRH neurons, changes response of GnRH neurons to input, and/or alters pituitary responsiveness to GnRH, and that a more pronounced resource scarcity would affect the parameters studied.

Significance Statement The stress and reproductive neuroendocrine systems interact, and early-life stress has reproductive consequences in humans. This study in mice rejected the hypotheses that an early-life stress, limited bedding and nesting (LBN), would delay sexual maturation and alter the response to an acute, layered, psychosocial stress (ALPS) in adulthood. ALPS disrupts the proestrous luteinizing hormone (LH) surge, which is critical for ovulation; this disruption is not altered by LBN. To assess a possible mechanism for this disruption, we conducted electrophysiological recording of gonadotropin-releasing hormone neurons to test if ALPS reduces excitatory GABAergic input to these cells. The frequency of GABAergic input was similar among groups, suggesting that LBN and ALPS act elsewhere in the broader neuroendocrine network controlling reproduction.