Genomics and Bioinformatics Core, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, USA.
Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore.
BMC Genomics. 2021 Jul 3;22(1):500. doi: 10.1186/s12864-021-07825-6.
Brown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling.
Maternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta.
These findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.
棕色脂肪组织(BAT)专门以热量的形式消耗能量。啮齿动物和人类的 BAT 介导的产热对于新生儿在出生后立即适应子宫外环境至关重要。然而,对于胎儿 BAT 发育是否以及如何在子宫内响应怀孕期间母体热环境的变化而受到调节,人们知之甚少。本研究使用 BL6 小鼠,评估了不同的母体环境温度(28°C 和 18°C)对胎盘和胎儿 BAT 转录组的影响,以测试母体冷暴露是否通过胎盘重塑影响胎儿 BAT 发育。
在 28°C 和 18°C 时,各组的妊娠期间母体体重增加、每个妊娠的平均胎儿数和胎盘重量没有差异。然而,在 18°C 组中,E18.5 时的平均胎儿体重比 28°C 组低 6%。在胎儿 BAT 中,妊娠期间的冷暴露诱导了参与从头脂生成和脂质代谢的基因的表达增加,同时降低了与肌肉细胞分化相关的基因的表达,这表明母体冷暴露可能通过抑制双向祖细胞中的肌源性谱系来促进胎儿棕色脂肪生成。在胎盘组织中,母体冷暴露与补体激活相关基因的上调和与肌肉收缩和肌动球蛋白丝滑动相关基因的下调有关。这些变化可能协调胎盘对母体冷暴露的适应,可能通过防止冷应激诱导的炎症损伤并调节胎盘的血管和血管外收缩系统来实现。
这些发现为环境冷温度被母体感知可调节胎盘和胎儿 BAT 组织的转录组提供了证据。观察到的基因表达变化的后果值得进一步研究。