卵巢上皮细胞中的孕激素信号调节免疫反应,以支持植入前胚胎发育
Emily A McGlade1,2, Jiude Mao1, Kalli K Stephens3
1Department of Obstetrics, Gynecology and Women's Health, School of Medicine, University of Missouri-Columbia, Columbia, MO 65211 USA.
Science advances
|April 18, 2025
概括
卵管中的孕激素信号对于早期怀孕的成功至关重要. 阻断卵巢细胞中的孕激素受体 (Pgr) 会增加炎症并损害胚胎发育,但NSAIDs可以帮助.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 第一个三个月的怀孕流产是常见的,强调需要了解卵巢功能.
- 孕激素受体 (Pgr) 在生殖过程中起着关键作用,但其在怀孕早期卵巢上皮细胞中的特定功能尚未完全理解.
研究的目的:
- 为了研究在卵管在植入前发育过程中表皮质孕激素受体 (Pgr) 在卵管中的作用.
- 探索连接Pgr信号,炎症和胚胎活力的分子机制.
主要方法:
- 一个条件淘汰赛小鼠模型 (Pgrd/d) 的生成,在卵巢上皮细胞中对Pgr进行了切除.
- 单细胞RNA测序以分析Pgrd/d卵管中的基因表达变化.
- 使用非类固醇抗炎药物 (NSAIDs) 药理上抑制炎症,并评估胚胎发育.
主要成果:
- 卵巢上皮细胞中Pgr的条件切除导致40%的病例中胚胎无法生存或发育迟缓.
- 单细胞RNA测序显示,在Pgrd/d卵巢细胞中,促炎性基因的表达增加,例如介质蛋白-22 (IL-22).
- 无抗药物治疗降低了IL-22水平,并挽救了Pgrd/d小鼠的胚胎发育,而IL-22暴露损害了母细胞囊扩张.
结论:
- 皮质Pgr信号传递对于维持卵管内稳定和支持正常的植入前胚胎发育至关重要.
- 卵管中的孕信号调节炎症,失调有助于怀孕失败.
- 这些发现为预防早期流产的诊断和治疗策略提供了潜在的目标.
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