Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States.
Center for Circadian Biology, University of California, San Diego, La Jolla, CA, United States.
Front Endocrinol (Lausanne). 2022 Aug 5;13:956169. doi: 10.3389/fendo.2022.956169. eCollection 2022.
Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, , 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 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 in arginine vasopressin ( ), vasoactive intestinal peptide ( ), both ( ), and neuromedin-s ( ) neurons. We demonstrate that the loss of 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 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 knockout.
生物钟系统的紊乱会改变生殖能力,尤其是在女性中。缺乏核心生物钟基因的小鼠是不育的,并且有神经内分泌紊乱的证据,包括缺乏促排卵黄体生成素 (LH) 激增和对外源 kisspeptin 的反应增强。在这里,我们探讨了 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 技术生成了四种小鼠品系,以创建精氨酸加压素 (AVP) 、血管活性肠肽 (VIP) 、两者 (AVP+VIP) 和神经降压素 -S (NMS) 神经元中 的条件性缺失。我们证明,这些群体中 的缺失对笼内昼夜活动和温度节律有很大影响。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、生育能力、kisspeptin 反应性和诱导性 LH 激增。我们在持续黑暗中没有发现生殖障碍的证据。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 敲除足以扰乱运动活动,但这种扰乱不足以重现全身 敲除的神经内分泌生殖效应。