Neurocience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109-5622.
Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-5622
eNeuro. 2024 Jul 29;11(7). doi: 10.1523/ENEURO.0125-24.2024. Print 2024 Jul.
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 to 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. Under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, and proestrous females reared in standard (STD) 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 STD-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, we conducted whole-cell voltage-clamp recordings. 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.
早期生活应激源会影响生殖发育,并改变对成年应激的反应。我们测试了从出生后第 4 天到第 11 天,以有限的铺料和巢穴(LBN)形式出现的资源匮乏是否会延迟雄性和雌性小鼠的性成熟,或改变它们对成年期急性、分层、心理社会应激(ALPS)的反应。与假设相反,LBN 的应用并未影响青春期的年龄和体重。在基础条件下和 ALPS 后,在标准(STD)或 LBN 环境中饲养的雄性、发情期雌性和发情前期雌性的皮质酮浓度相似。当 ALPS 在发情前期的早上应用时,会破坏大多数小鼠的促黄体生成素(LH)激增;资源匮乏并没有改变这种影响。在这项研究中,后代缺乏影响可能与 CBA 母鼠对该范式的反应较为温和有关。虽然 LBN 母鼠比 STD 饲养的母鼠更频繁地离开巢穴,其幼崽在第 11 天也比 STD 饲养的幼崽小,但在第 11 天,母鼠皮质酮浓度相似。为了测试 ALPS 是否通过减弱发情前期下午对促性腺激素释放激素(GnRH)神经元的兴奋性 GABA 能传入的增加来破坏 LH 激增,我们进行了全细胞膜片钳记录。LBN、ALPS 或它们的相互作用并没有改变 GnRH 神经元中 GABA 能突触后电流的频率。仍然有可能是 ALPS 作用于 GnRH 神经元的传入,改变 GnRH 神经元对输入的反应,和/或改变垂体对 GnRH 的反应,而更明显的资源匮乏会影响所研究的参数。