关键词: GABA GnRH LH early-life stress psychosocial stress reproduction

Mesh : Animals Corticosterone / blood Female Stress, Psychological / metabolism Luteinizing Hormone / metabolism blood Male Mice, Inbred CBA Mice Sexual Maturation / physiology Nesting Behavior / physiology Neurons / metabolism Animals, Newborn

来  源:   DOI:10.1523/ENEURO.0125-24.2024   PDF(Pubmed)

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 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.
摘要:
早期生活压力源可以影响生殖发育并改变对成人压力的反应。我们测试了出生后(PND)4-11天以有限的垫层和筑巢(LBN)形式的资源稀缺性是否延迟了雄性和雌性小鼠的性成熟和/或改变了对急性,分层,成年后的社会心理压力(ALPS)。与假设相反,青春期的年龄和质量不受LBN当前应用的影响。Further,在基础条件下和ALPS后,男性的皮质酮浓度,女性女性,或在标准或LBN环境中饲养的雌性雌性相似。ALPS在发情期早晨使用时会破坏大多数小鼠的促黄体生成素(LH)激增;资源稀缺不会改变这种影响。在这项研究中,后代效应的缺乏可能与CBA大坝对范式的温和反应有关。虽然LBN大坝更频繁地离开巢穴,它们的后代在PND11上比标准饲养的后代小,大坝皮质酮浓度在PND11上相似。为了测试ALPS是否通过在发情期下午减弱对促性腺激素释放激素(GnRH)神经元的兴奋性GABA能输入的增加来破坏LH激增,进行了全细胞电压钳记录.GnRH神经元中GABA能突触后电流的频率未被LBN改变,阿尔卑斯,或他们的互动。ALPS可能作用于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,更明显的资源稀缺性会影响所研究的参数。重要性声明压力和生殖神经内分泌系统相互作用,早期生活压力对人类有生殖后果。这项针对小鼠的研究拒绝了早期生活压力的假设,有限的垫层和嵌套(LBN),会延迟性成熟并改变对急症的反应,分层,成年后的社会心理压力(ALPS)。ALPS会破坏发情的黄体生成素(LH)激增,这对排卵至关重要;LBN不会改变这种破坏。为了评估这种破坏的可能机制,我们进行了促性腺激素释放激素神经元的电生理记录,以测试ALPS是否减少了对这些细胞的兴奋性GABA能输入.各组之间GABA能输入的频率相似,这表明LBN和ALPS在控制生殖的更广泛的神经内分泌网络中的其他地方起作用。
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