Ge Yuhang, Teng Ruxin, Jia Zhaoyu, Li Yongyue, Lu Yafang, Yuan Jia
Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
J Transl Med. 2025 Apr 28;23(1):481. doi: 10.1186/s12967-025-06424-3.
Preterm birth (PTB) is a major cause of neonatal morbidity and mortality worldwide, with infection and inflammation being the most common triggers. However, many cases of preterm labor have unknown causes. The maternal decidua is a highly dynamic and heterogeneous region, serving as the nexus at the maternal-fetal interface, connecting the mother and the fetus. Increasing evidence suggests that the maternal decidua plays a crucial role in the initiation of labor. Nerve growth factor (NGF), is an important member of the neurotrophin family and is identified to play a crucial role in initiating the decidual response.
To investigate whether NGF contributes to preterm birth via lipid peroxidation-dependent pathways, we selected both NGF and erastin (a pharmacological lipid peroxidation inducer) for parallel experimental treatments to examine how these pathways mediate the initiation of parturition. Mice were administered intraperitoneal injections of NGF and erastin. Gestational durations less than 19.5 days were classified as preterm birth. This study employed biological technologies and experimental methods to explore the initiation of delivery and the associated signaling pathways.
Elevated NGF levels in late-stage pregnancy increased the incidence of preterm birth in mice, independent of decidual senescence, placenta abnormal structure and ovarian dysfunction. Instead, NGF treatment activated lipid peroxidation and upregulated inflammatory markers in maternal decidua, particularly cyclooxygenase enzymes, which are critical for labor initiation. Notably, administration of erastin corroborated these findings, leading to similar outcomes in preterm labor.
This study reveals the pivotal role of NGF signaling in promoting excessive lipid peroxidation to disrupt decidual homeostasis and ultimately triggering preterm labor in mice.
早产是全球新生儿发病和死亡的主要原因，感染和炎症是最常见的诱因。然而，许多早产病例病因不明。母体蜕膜是一个高度动态且异质性的区域，是母胎界面的枢纽，连接着母亲和胎儿。越来越多的证据表明，母体蜕膜在分娩发动中起关键作用。神经生长因子（NGF）是神经营养因子家族的重要成员，被认为在启动蜕膜反应中起关键作用。
为了研究NGF是否通过脂质过氧化依赖性途径导致早产，我们选择NGF和艾拉司亭（一种药理学上的脂质过氧化诱导剂）进行平行实验处理，以研究这些途径如何介导分娩发动。给小鼠腹腔注射NGF和艾拉司亭。妊娠期少于19.5天被归类为早产。本研究采用生物技术和实验方法来探索分娩发动及相关信号通路。
妊娠晚期NGF水平升高增加了小鼠早产的发生率，与蜕膜衰老、胎盘结构异常和卵巢功能障碍无关。相反，NGF处理激活了脂质过氧化，并上调了母体蜕膜中的炎症标志物，特别是环氧化酶，这些酶对分娩发动至关重要。值得注意的是，给予艾拉司亭证实了这些发现，导致早产方面有类似结果。
本研究揭示了NGF信号在促进过度脂质过氧化以破坏蜕膜稳态并最终引发小鼠早产中的关键作用。
