Zou Jianwei, Wei Lili, Liang Yishan, Zou Juhong, Cheng Pengfei, Mo Zhihua, Sun Wenyue, Wei Yirong, Lu Jun, Li Wenman, Shen Yulong, Deng Xiaoyan, Huang Yanna, Jiang Qinyang
College of Animal Science and Technology, Guangxi University, Nanning 530004, China.
Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning 530004, China.
Animals (Basel). 2025 Jul 25;15(15):2189. doi: 10.3390/ani15152189.
Heat stress (HS) is a major environmental factor negatively impacting the reproductive performance of livestock. This study investigates the molecular mechanisms of heat stress on the hypothalamic-pituitary-ovarian (HPO) axis in Hu sheep. A heat-stressed animal model was established, and high-throughput RNA sequencing (RNA-seq) was employed to analyze gene expression in the hypothalamus, pituitary, and ovarian tissues of both control and heat-stressed groups. The results revealed significant changes in estrus behavior, hormone secretion, and reproductive health in heat-stressed sheep, with a shortened estrus duration, prolonged estrous cycles, and decreased levels of FSH, LH, E, and P4. A total of 520, 649, and 482 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary, and ovary, respectively. The DEGs were enriched in pathways related to hormone secretion, neurotransmission, cell proliferation, and immune response, with significant involvement of the p53 and cAMP signaling pathways. Tissue-specific responses to heat stress were observed, with distinct regulatory roles in each organ, including GPCR activity and cytokine signaling in the hypothalamus, calcium-regulated exocytosis in the pituitary, and cilium assembly and ATP binding in the ovary. Key genes such as , , and were identified as central to the coordinated regulation of the HPO axis. These findings provide new insights into the molecular basis of heat stress-induced impairments in reproductive function-manifested by altered estrous behavior, reduced hormone secretion (FSH, LH, E, and P4), and disrupted gene expression in the hypothalamic-pituitary-ovarian (HPO) axis-and offer potential targets for improving heat tolerance and reproductive regulation in sheep.
热应激（HS）是对家畜繁殖性能产生负面影响的主要环境因素。本研究调查热应激对湖羊下丘脑 - 垂体 - 卵巢（HPO）轴的分子机制。建立了热应激动物模型，并采用高通量RNA测序（RNA-seq）分析对照组和热应激组下丘脑、垂体和卵巢组织中的基因表达。结果显示，热应激绵羊的发情行为、激素分泌和生殖健康发生了显著变化，发情持续时间缩短，发情周期延长，促卵泡生成素（FSH）、促黄体生成素（LH）、雌激素（E）和孕酮（P4）水平降低。分别在丘脑下部、垂体和卵巢中鉴定出520、649和482个差异表达基因（DEG）。这些DEG富集在与激素分泌、神经传递、细胞增殖和免疫反应相关的通路中，p53和环磷酸腺苷（cAMP）信号通路显著参与其中。观察到各组织对热应激的特异性反应，每个器官都有独特的调节作用，包括下丘脑中的G蛋白偶联受体（GPCR）活性和细胞因子信号传导、垂体中的钙调节胞吐作用以及卵巢中的纤毛组装和ATP结合。诸如[具体基因名称未给出]等关键基因被确定为HPO轴协调调节的核心。这些发现为热应激导致的生殖功能损害的分子基础提供了新见解，热应激导致发情行为改变、激素分泌减少（FSH、LH、E和P4）以及下丘脑 - 垂体 - 卵巢（HPO）轴基因表达紊乱，并为提高绵羊耐热性和生殖调节提供了潜在靶点。
