Department of Animal and Range Sciences, Montana State University, Bozeman, MT, USA.
Department of Dairy Science, Virginia Tech, Blacksburg, VA, USA.
J Anim Sci. 2022 Jul 1;100(7). doi: 10.1093/jas/skac090.
Exposure to maternal obesity in utero is associated with marked developmental effects in offspring that may not be evident until adulthood. Mechanisms regulating the programming effects of maternal obesity on fetal development have been reported, but little is known about how maternal obesity affects the earliest periods of embryonic development. This work explored how obesity influences endometrial gene expression during the peri-implantation period using a sheep model. Ewes were assigned randomly to diets that produced an obese state or maintained a lean state. After 4 mo, obese and lean ewes were bred and then euthanized at day 14 post-breeding. The uterus was excised, conceptuses were flushed, and endometrial tissue was collected. Isolated RNA from endometrial tissues (n = 6 ewes/treatment) were sequenced using an Illumina-based platform. Reads were mapped to the Ovis aries genome (Oar_4.0). Differential gene expression was determined, and results were filtered (false discovery rate ≤ 0.05 and ≥2-fold change, ≥0.2 reads/kilobase/million reads). Differentially expressed genes (DEGs) were identified (n = 699), with 171 downregulated and 498 upregulated in obese vs. lean endometrium, respectively. The most pronounced gene ontology categories identified were cellular process, metabolic process, and biological regulation. Enrichments were detected within the DEGs for genes involved with immune system processes, negative regulation of apoptosis, cell growth, and cell adhesion. A literature search revealed that 125 DEGs were associated with either the trophoblast lineage or the placenta. Genes within this grouping were involved with wingless/integrated signaling, angiogenesis, and integrin signaling. In summary, these data indicate that the peri-implantation endometrium is responsive to maternal obesity. Transcript profile analyses suggest that the endometrial immune response, adhesion, and angiogenesis may be especially susceptible to obesity. Thus, alterations in uterine transcript profiles during early embryogenesis may be a mechanism responsible for developmental programming following maternal obesity exposure in utero.
子宫内暴露于母体肥胖与后代明显的发育效应有关，这些效应可能直到成年后才显现。已经报道了调节母体肥胖对胎儿发育编程效应的机制，但对于母体肥胖如何影响胚胎发育的最早阶段知之甚少。本研究使用绵羊模型探索了肥胖如何影响着床前阶段的子宫内膜基因表达。将母羊随机分配到产生肥胖状态或维持瘦状态的饮食中。4 个月后，肥胖和瘦的母羊配种，然后在配种后第 14 天安乐死。取出子宫，冲洗胚胎，收集子宫内膜组织。从子宫内膜组织（n = 6 只母羊/处理）中分离 RNA，使用基于 Illumina 的平台进行测序。将读取映射到 Ovis aries 基因组（Oar_4.0）。确定差异表达基因，并过滤结果（错误发现率≤0.05 和≥2 倍变化，≥0.2 个读取/每千碱基/每百万读取）。鉴定出差异表达基因（DEGs）（n = 699），肥胖组与瘦组相比，分别有 171 个下调和 498 个上调。鉴定到的最显著的基因本体类别是细胞过程、代谢过程和生物调节。在 DEGs 中检测到与免疫系统过程、细胞凋亡负调节、细胞生长和细胞黏附相关的基因富集。文献检索显示，125 个 DEGs 与滋养层谱系或胎盘有关。该分组中的基因参与 Wnt/整合信号、血管生成和整合素信号。总之，这些数据表明着床前子宫内膜对母体肥胖有反应。转录谱分析表明，子宫内膜免疫反应、黏附和血管生成可能特别容易受到肥胖的影响。因此，早期胚胎发生过程中子宫转录谱的改变可能是母体肥胖暴露后发育编程的机制之一。
