Zhang Nan, Yu Meng, Zhao Qianru, Feng Bing, Deng Yue, Bean Jonathan C, Liu Qingzhuo, Eappen Benjamin P, He Yang, Conde Kristine M, Liu Hailan, Yang Yongjie, Tu Longlong, Wang Mengjie, Li Yongxiang, Yin Na, Liu Hesong, Han Junying, Threat Darah Ave, Xu Nathan, Smiley Taylor, Xu Pingwen, Chen Lulu, Zeng Tianshu, He Yanlin, Wang Chunmei
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, Hubei 430022, China; Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, Hubei 430022, China; Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, Hubei 430022, China.
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Mol Metab. 2025 Mar;93:102108. doi: 10.1016/j.molmet.2025.102108. Epub 2025 Feb 3.
This study aims to investigate how reproductive experience (RE) alters thermal preference and thermoregulation in female mice, with a focus on estrogen receptor alpha (ERα)-expressing neurons in the preoptic area (POA).
Thermal preference and body temperature were measured in female mice with and without RE, and virgin female mice with selective deletion of ERα from the POA (ERα-KO). The number and activity of ERα-expressing POA neurons (ERα) were assessed using immunohistochemistry and in vitro electrophysiology in response to temperature changes and ERα agonist.
We showed that female mice prefer a cooler environment starting from late pregnancy and persisting long term postpartum. Female mice with RE (>4 weeks post-weaning) displayed lower body temperature and a lower thermal preferred temperature, and lost preference for warm environments (30 °C) but preserved avoidance of cold environments (15 °C). This was associated with a significant decrease in the number of ERα neurons. Importantly, virgin female ERα-KO mice displayed lower thermal preferred temperature and impaired warm preference, mimicking RE mice. We further found that distinct ERα subpopulations can be regulated by temperature changes with or without presynaptic blockers, and by ERα agonist. More importantly, RE decreased the number of warm-activated ERα neurons and reduced the excitatory effects of warmth and estrogen-ERα signaling, while cold-activated ERα neurons were slightly enhanced in female mice with RE.
Our results support that the thermosensing ability and estrogenic effects in ERα neurons are regulated by reproductive experience, altering thermal preference.
本研究旨在探讨生殖经历（RE）如何改变雌性小鼠的热偏好和体温调节，重点关注视前区（POA）中表达雌激素受体α（ERα）的神经元。
对有或无生殖经历的雌性小鼠以及视前区选择性缺失ERα的处女雌性小鼠（ERα-KO）进行热偏好和体温测量。使用免疫组织化学和体外电生理学方法，评估表达ERα的视前区神经元（ERα）的数量和活性，以响应温度变化和ERα激动剂。
我们发现，雌性小鼠从妊娠后期开始就偏好较凉爽的环境，并且在产后长期保持这种偏好。有生殖经历的雌性小鼠（断奶后>4周）体温较低，热偏好温度也较低，对温暖环境（30°C）的偏好丧失，但仍保持对寒冷环境（15°C）的回避。这与ERα神经元数量的显著减少有关。重要的是，处女雌性ERα-KO小鼠表现出较低的热偏好温度和受损的温暖偏好，类似于有生殖经历的小鼠。我们进一步发现，不同的ERα亚群可通过有无突触前阻滞剂时的温度变化以及ERα激动剂进行调节。更重要的是，生殖经历减少了温暖激活的ERα神经元数量，并降低了温暖和雌激素-ERα信号的兴奋作用，而在有生殖经历的雌性小鼠中，寒冷激活的ERα神经元略有增强。
我们的结果支持ERα神经元中的热敏能力和雌激素效应受生殖经历调节，从而改变热偏好。
