Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S.
Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S.
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DOI：
10.3389/fendo.2022.956169
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发表时间：
2022
影响因子：
5.2
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中科院分区：
文献类型：
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昼夜节律系统的破坏会改变生殖能力，尤其是女性。缺乏核心生物钟基因 Bmal1 的小鼠不育，并且有神经内分泌紊乱的证据，包括排卵前黄体生成素 (LH) 激增的缺失和对外源性 Kisspeptin 的反应增强。在这里，我们探讨了 Bmal1 在已知投射到神经内分泌轴的视交叉上核 (SCN) 神经元群体中的作用。我们使用 Cre/Lox 技术生成了四个小鼠系，以在精氨酸加压素 (Bmal1fl/fl:Avpcre )、血管活性肠肽 (Bmal1fl/fl:Vipcre )、两者 (Bmal1fl/fl:Avpcre+Vipcre ) 和神经调节素-s (Bmal1fl/fl:Nmscre ) 神经元中条件性删除 Bmal1。我们证明，这些群体中 Bmal1 的缺失对家笼昼夜节律活动和温度节律有重大影响。尽管如此，我们发现这些品系的雌性小鼠表现出正常的发情周期、繁殖力、吻肽反应性和诱导性 LH 激增。我们没有发现在持续黑暗中生殖受到破坏的证据。总体而言，我们的结果表明，虽然 AVP、VIP 或 NMS 神经元中的条件性 Bmal1 敲除足以破坏运动活动，但这种破坏不足以概括全身 Bmal1 敲除的神经内分泌生殖效应。
Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, Bmal1, are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsiveness to exogenous kisspeptin. Here, we explore the role of Bmal1 in suprachiasmatic nucleus (SCN) neuron populations known to project to the neuroendocrine axis. We generated four mouse lines using Cre/Lox technology to create conditional deletion of Bmal1 in arginine vasopressin (Bmal1fl/fl:Avpcre ), vasoactive intestinal peptide (Bmal1fl/fl:Vipcre ), both (Bmal1fl/fl:Avpcre+Vipcre ), and neuromedin-s (Bmal1fl/fl:Nmscre ) neurons. We demonstrate that the loss of Bmal1 in these populations has substantial effects on home-cage circadian activity and temperature rhythms. Despite this, we found that female mice from these lines demonstrated normal estrus cycles, fecundity, kisspeptin responsiveness, and inducible LH surge. We found no evidence of reproductive disruption in constant darkness. Overall, our results indicate that while conditional Bmal1 knockout in AVP, VIP, or NMS neurons is sufficient to disrupted locomotor activity, this disruption is insufficient to recapitulate the neuroendocrine reproductive effects of the whole-body Bmal1 knockout.
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