Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Animal Sciences, University of Florida, Gainesville, FL 32611, USA.
J Anim Sci. 2022 Oct 1;100(10). doi: 10.1093/jas/skac186.
Prenatal hyperthermia has immediate and long-term consequences on dairy cattle growth, immunity, and productivity. While changes in the molecular architecture are reported in the mature mammary gland (MG), any influence on early-life mammary development is unknown. Herein, we characterize the impact of late-gestation in utero heat stress on heifer mammary gross and cellular morphology at early-life developmental stages (i.e., birth and weaning). During summer, pregnant dams were exposed to environmental heat stress (shade of a free-stall barn) or offered active cooling (shade, fans, and water soakers) for 54 ± 5 d before parturition (avg. temperature-humidity index = 79). Heifer calves born to these dams were either in utero heat-stressed (IU-HT; n = 36) or in utero cooled (IU-CL; n = 37) and were managed as a single cohort thereafter. A subset of heifers was euthanized at birth (d0; n = 8/treatment; 4.6 ± 2.3 h after birth) and after weaning (d63; n = 8/treatment; 63.0 ± 1.5 d) to harvest the whole MG. An ultrasound of rear mammary parenchyma (MPAR) was taken prior to d63 and correlated to harvested MPAR cross-sectional area and weight. Portions of mammary fat pad (MFP) and MPAR were preserved for compositional and histological analysis, including ductal structure number and cross-sectional area, connective tissue area, and adipocyte number and cross-sectional area. Cellular proliferation in MPAR was assessed via Ki-67 immunohistochemistry. Relative to IU-CL heifers, the MGs of IU-HT heifers were shorter in length at d0 and d63 (P ≤ 0.02). There were moderate correlations between d63 ultrasound and harvest measures. The IU-HT heifers had reduced MG and MFP mass at d0 and d63 (P ≤ 0.05), whereas MPAR mass was reduced only at d0 (P = 0.01). IU-HT heifers had greater MPAR protein and DNA content at d63 (P ≤ 0.04), but there were no MFP compositional differences (P ≥ 0.12). At d0, IU-HT heifers had fewer MPAR ductal structures (P ≤ 0.06), but there were no differences at d63. Yet, MPAR luminal and total ductal structure cross-sectional areas of IU-HT heifers were reduced at both d0 and d63 (P ≤ 0.01). The MFP adipocytes of IU-HT heifers were smaller at d0 (P ≤ 0.01), but differences were not detected at d63. The IU-HT heifers had diminished MPAR total, stromal, and epithelial cellular proliferation at both d0 and d63 (P < 0.01). Prenatal hyperthermia derails dairy calf early-life mammary development with potential carry-over consequences on future synthetic capacity.
产前高热对奶牛的生长、免疫和生产力有直接和长期的影响。虽然成熟乳腺（MG）中报道了分子结构的变化，但对早期乳腺发育的任何影响尚不清楚。在此，我们描述了妊娠后期宫内热应激对新生牛乳腺在生命早期发育阶段（即出生和断奶）的大体和细胞形态的影响。在夏季，怀孕的母羊在分娩前（平均温度-湿度指数= 79）暴露于环境热应激（自由站立牛舍的阴凉处）或接受主动冷却（阴凉处、风扇和水浸式冷却器）54±5 天。来自这些母羊的新生小牛要么在宫内受到热应激（IU-HT；n=36），要么在宫内受到冷却（IU-CL；n=37），此后作为单一队列进行管理。一小部分小牛在出生时（d0；n=8/处理；出生后 4.6±2.3 小时）和断奶时（d63；n=8/处理；63.0±1.5 天）被安乐死，以收获整个 MG。在 d63 之前对后乳腺实质（MPAR）进行超声检查，并与收获的 MPAR 横截面积和重量相关。部分乳腺脂肪垫（MFP）和 MPAR 被保存用于组成和组织学分析，包括导管结构数量和横截面积、结缔组织面积以及脂肪细胞数量和横截面积。通过 Ki-67 免疫组化评估 MPAR 中的细胞增殖。与 IU-CL 小牛相比，IU-HT 小牛的 MG 在 d0 和 d63 时更短（P≤0.02）。d63 超声与收获测量之间存在中度相关性。IU-HT 小牛在 d0 和 d63 时 MG 和 MFP 质量减少（P≤0.05），而仅在 d0 时 MPAR 质量减少（P=0.01）。IU-HT 小牛在 d63 时 MPAR 蛋白和 DNA 含量更高（P≤0.04），但 MFP 组成没有差异（P≥0.12）。在 d0 时，IU-HT 小牛的 MPAR 导管结构较少（P≤0.06），但在 d63 时没有差异。然而，IU-HT 小牛在 d0 和 d63 时的 MPAR 管腔和总导管结构横截面积均减少（P≤0.01）。IU-HT 小牛的 MFP 脂肪细胞在 d0 时较小（P≤0.01），但在 d63 时未检测到差异。IU-HT 小牛在 d0 和 d63 时的 MPAR 总细胞、基质细胞和上皮细胞增殖均减少（P<0.01）。产前高热打乱了奶牛新生牛早期的乳腺发育，对未来的合成能力可能产生持续的影响。
