Department of Pediatrics, Division of Neonatology and Newborn Nursery, University of Wisconsin-Madison, 1300 University Avenue, SMI 112, Madison, WI 53706, USA.
Department of Pediatrics, Division of Neonatology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Cells. 2024 Oct 19;13(20):1735. doi: 10.3390/cells13201735.
The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23-42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood-retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP.
胎儿器官的发育可能会受到母体循环中系统性变化的影响,而胎盘在维持妊娠内环境和营养交换方面起着关键作用。在临床产科中,催产素(OXT)常用于引产。为了探讨 OXT 在胎盘内环境中的潜在作用,我们比较了接受产前 OXT 或自然分娩的新生儿(23-42 周妊娠)脐带血中的 OXT 水平。我们之前的研究表明,在形成血视网膜屏障中必不可少的催产素受体(OXTR)在视网膜色素上皮(RPE)中表达。我们假设围产期 OXT 给药可能会影响神经视网膜及其脉管系统的发育,为早产儿视网膜病变(ROP)等视网膜疾病提供治疗潜力。使用商业 OXT ELISA 试剂盒测量血浆 OXT 水平。用 OXT(10 μM)处理人胎儿 RPE(hfRPE)细胞,通过 RNA 测序评估基因表达,发现 14 个下调和 32 个上调基因。为了验证这些差异表达基因(DEGs),将 hfRPE 细胞暴露于 OXT(0.01、0.1、1 或 10 μM)12 小时,然后通过实时 PCR 进行 RNA 分析。进行功能、富集和网络分析(基因本体术语、FunRich、Cytoscape)以预测受影响的途径。这项转化研究表明,OXT 可能穿过胎盘,改变胎儿 OXT 浓度。RNA 测序确定了 46 个涉及重要代谢和信号通路以及关键细胞成分的 DEGs。我们的结果表明,围产期 OXT 的给药可能会影响神经视网膜和视网膜血管的发育,使 OXT 成为包括 ROP 在内的发育性眼病的潜在治疗选择。