Heat stress–induced apoptosis in granulosa cells is mediated by multiple apoptotic signaling pathways, including endoplasmic reticulum (ER) stress. Boron is a naturally occurring trace element with several cytoprotective properties. Nonetheless, the molecular mechanisms involved in the protective functions of boron in granulosa cells undergoing apoptosis caused by heat stress (HS) remain unclear. In this study, we investigated the role of boric acid, a predominant chemical form of boron, in HS-induced apoptotic damage in mouse granulosa cells (mGCs) and explored the underlying mechanisms. We found that HS treatment suppressed cell viability; increased the apoptotic rate of cells; potentiated the activity of caspase-3, a key player in the caspase-mediated apoptotic signaling pathway; and activated ER stress markers, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) in mGCs. However, boric acid treatment effectively alleviated the effects of both HS-induced and thapsigargin (an ER stress agonist)–induced apoptosis, such as the enhanced activity of caspase-3 and increase in GRP78 and CHOP expression. Moreover, treatment with 4-phenylbutyrate (4-PBA), an ER stress antagonist, significantly attenuated these HS-induced adverse effects in mGCs. In addition, boric acid supplementation in the culture medium significantly restored the decreased estradiol levels in heat-treated mGCs. The administration of boric acid to female mice previously exposed to hyperthermal conditions effectively restored the levels of serum estradiol in vivo. Collectively, these findings suggest that HS induces apoptosis in mGCs via ER stress pathways and that boron has a protective effect against these adverse effects. This study provides novel insights into the benefits of using boron against heat-induced apoptosis.

热应激诱导的颗粒细胞凋亡是由多种凋亡信号通路介导的，包括内质网应激。硼是具有多种细胞保护特性的天然痕量元素。然而，尚不清楚参与热应激（HS）引起的细胞凋亡的颗粒细胞中硼保护功能的分子机制。在这项研究中，我们调查了硼酸（硼的一种主要化学形式）在HS诱导的小鼠颗粒细胞（mGCs）引起的细胞凋亡中的作用，并探讨了其潜在机制。我们发现HS处理抑制了细胞活力。增加细胞凋亡率；增强了caspase-3的活性，caspase-3是caspase介导的凋亡信号通路中的关键参与者；和激活的ER压力标记，包括mGC中的葡萄糖调节蛋白78（GRP78）和CCAAT /增强子结合蛋白（C / EBP）同源蛋白（CHOP）。但是，硼酸处理可有效减轻HS诱导的和毒胡萝卜素（一种ER应激激动剂）诱导的细胞凋亡，例如增强caspase-3活性以及增加GRP78和CHOP表达。此外，ER应激拮抗剂4-苯基丁酸酯（4-PBA）的治疗显着减轻了这些HS诱导的mGC中的不良反应。另外，在培养基中补充硼酸可显着恢复热处理过的mGC中雌二醇水平的降低。向先前暴露于高温条件下的雌性小鼠施用硼酸可有效恢复体内血清雌二醇的水平。总的来说，这些发现表明，HS通过ER应激途径诱导mGC中的细胞凋亡，而硼对这些不良反应具有保护作用。这项研究为使用硼对抗热诱导的细胞凋亡的益处提供了新颖的见解。