Halloran Katherine M, Saadat Nadia, Pallas Brooke, Vyas Arpita K, Padmanabhan Vasantha
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.
Mol Cell Endocrinol. 2025 Jun 1;603:112546. doi: 10.1016/j.mce.2025.112546. Epub 2025 Apr 12.
An understanding of the inner workings of the placenta is imperative to elucidate how the maternal and fetal compartments coordinate to mediate fetal development. The two compartments can be separated and studied before term in sheep, a feat not possible in humans, thus providing a valuable translational model. This study investigated differential expression of gene signaling networks in the maternal and fetal compartments of the placenta and explored the potential influence of fetal sex. On approximately gestational day 120 (term: 147 days), ewes were euthanized and fetuses removed and sexed. Placentomes [n = 5 male, n = 3 female] were collected, and caruncles (maternal) and cotyledons (fetal) were separated and sequenced to assess RNA expression. Analysis revealed 2627 differentially expressed genes (FDR<0.01, abslog2FC ≥ 2) contributing to key transcriptional differences between maternal and fetal compartments, which suggested that the maternal compartment drives extracellular signaling at the interface whereas the fetal compartment controls internal mechanisms crucial for fetal-placental development. X-chromosome inactivation equalized expression of a vast majority of X-linked genes in the fetal compartment. Additionally, the female placenta had more fine-tuned regulation of key pathways for fetal-placental development, such as DNA replication, mRNA surveillance, and RNA transport, compared to males, which had enrichment of metabolic pathways including TCA cycle and galactose metabolism. These findings, in addition to supporting differences in expression in the maternal and fetal placental compartments and the possible influence of fetal sex, offer a transcriptional platform to compare placental perturbations that occur at the maternal-fetal interface that contribute to adverse pregnancy outcomes.
了解胎盘的内部运作机制对于阐明母体和胎儿部分如何协同调节胎儿发育至关重要。在绵羊中，可以在足月前分离并研究这两个部分，这在人类中是无法实现的，因此提供了一个有价值的转化模型。本研究调查了胎盘母体和胎儿部分基因信号网络的差异表达，并探讨了胎儿性别的潜在影响。在大约妊娠第120天（足月：147天），对母羊实施安乐死，取出胎儿并确定性别。收集胎盘叶[雄性n = 5，雌性n = 3]，分离出肉阜（母体）和子叶（胎儿）并进行测序以评估RNA表达。分析揭示了2627个差异表达基因（FDR<0.01，abslog2FC≥2），这些基因导致了母体和胎儿部分之间的关键转录差异，这表明母体部分在界面处驱动细胞外信号传导，而胎儿部分控制对胎儿-胎盘发育至关重要的内部机制。X染色体失活使胎儿部分中绝大多数X连锁基因的表达趋于平衡。此外，与雄性相比，雌性胎盘对胎儿-胎盘发育的关键途径（如DNA复制、mRNA监测和RNA转运）具有更精细的调节，而雄性则富集了包括三羧酸循环和半乳糖代谢在内的代谢途径。这些发现除了支持胎盘母体和胎儿部分表达的差异以及胎儿性别的可能影响外，还提供了一个转录平台，用于比较发生在母胎界面处导致不良妊娠结局的胎盘扰动。
