Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706.
Department of Animal Sciences, University of Florida, Gainesville, FL 32608.
J Dairy Sci. 2024 Aug;107(8):6308-6321. doi: 10.3168/jds.2023-24606. Epub 2024 Apr 4.
Maternal heat stress during late pregnancy can lead to intrauterine hyperthermia and affect fetal hypothalamic-pituitary-adrenal axis development and function. Herein, we investigated the effects of chronic environmental heat stress exposure of Holstein cows in the last 2 mo of gestation on their offspring's adrenal gland histomorphology and transcriptome. Cows in their last 54 ± 5 d of gestation were either heat stressed (housed under the shade of a freestall barn) or provided heat stress abatement via active cooling (via water soakers and fans) during a subtropical summer (temperature-humidity index >68). Respiration rate (RR) and skin temperature (ST) were elevated in heat-stressed dams relative to the cows with access to heat abatement (23 breaths/min and 2°C higher for RR and ST, respectively). Heifers born to heat-stressed cows experienced heat stress in utero (HS), whereas heifers born to actively cooled cows did not (CL). The adrenal gland was harvested from 6 heifers per group that were euthanized at birth (d 0; n = 12) or 1 wk after weaning (d 63; n = 12). Circulating cortisol was measured from blood samples collected weekly throughout the preweaning period. At d 63, heifers that experienced HS while developing in utero had heavier adrenal glands, with a greater total tissue surface area and thickness of the zona glomerulosa (ZG), fasciculata (ZF), and reticularis (ZR), compared with CL heifers. In addition, the adrenal gland of HS heifers had fewer cells in the ZG, more and larger cells in the ZF, and larger cells in the ZR, relative to CL heifers. Although no changes in circulating cortisol were observed through the preweaning period, the transcriptomic profile of the adrenal tissue was altered by fetal exposure to hyperthermia. Both at birth and on d 63, approximately 30 pathways were differentially expressed in the adrenal glands of HS heifers relative to CL. These pathways were associated with immune function, inflammation, prolactin signaling, cell function, and calcium transport. Upstream regulators significantly activated or inhibited in the adrenal glands of heifers exposed to intrauterine hyperthermia were identified. Maternal exposure to heat stress during late gestation caused an enlargement of their offspring's adrenal glands by inducing ZG and ZF cell hypertrophy, and caused gene expression changes. These phenotypic, histological, and molecular changes in the adrenal gland might lead to alterations in stress, immune, and metabolic responses later in life.
母体妊娠后期的热应激会导致宫内过热，影响胎儿下丘脑-垂体-肾上腺轴的发育和功能。在这里，我们研究了荷斯坦奶牛妊娠最后 2 个月暴露于慢性环境热应激对其后代肾上腺组织形态学和转录组的影响。妊娠最后 54 ± 5 天的奶牛要么处于热应激状态（在牛舍的阴凉处饲养），要么通过主动降温（通过水浸湿器和风扇）在亚热带夏季（温度-湿度指数>68）缓解热应激。与有降温措施的奶牛相比，热应激的奶牛呼吸频率（RR）和皮肤温度（ST）升高（RR 和 ST 分别升高 23 次/分钟和 2°C）。出生时（d0；n=12）或断奶后 1 周（d63；n=12），从每组 6 头新生小母牛中采集肾上腺。在整个断奶前期间每周采集血液样本测量循环皮质醇。在 d63，在子宫内经历热应激的小母牛的肾上腺更重，总组织表面积更大，球状带（ZG）、束状带（ZF）和网状带（ZR）的厚度也更大，而 CL 小母牛则没有。此外，与 CL 小母牛相比，HS 小母牛的 ZG 细胞数量减少，ZF 细胞数量增加且体积更大，ZR 细胞体积更大。尽管在整个断奶前期间没有观察到循环皮质醇的变化，但胎儿暴露于高热会改变肾上腺组织的转录组谱。在 HS 小母牛和 CL 小母牛的肾上腺组织中，约有 30 个通路在出生时和 d63 时表达不同。这些途径与免疫功能、炎症、催乳素信号、细胞功能和钙转运有关。在子宫内暴露于热应激的小母牛肾上腺中，显著激活或抑制的上游调节剂被识别。母体妊娠后期暴露于热应激导致小母牛后代的肾上腺增大，这是通过诱导 ZG 和 ZF 细胞肥大引起的，并导致基因表达变化。肾上腺的这些表型、组织学和分子变化可能导致生命后期应激、免疫和代谢反应的改变。
