产前接触地塞米松后，小鼠胎儿卵巢发育受到阶段、剂量和病程依赖性破坏
Stage-, dose- and course-dependent disruption of mice fetal ovarian development following prenatal dexamethasone exposure.
摘要(中文译文)
地塞米松是一种合成糖皮质激素，广泛用于孕期预防早产儿呼吸窘迫综合征。尽管我们前期工作已证实，产前多次地塞米松暴露（PDE）会损害子代卵巢功能并具有跨代效应，但暴露阶段、剂量和疗程的具体影响仍不明确。妊娠昆明小鼠于妊娠中晚期（GD14-15）或妊娠晚期（GD16-17）接受低/中/高剂量地塞米松处理，采用单疗程或连续两疗程给药。于GD18收集胎鼠卵巢，评估形态学、细胞增殖/凋亡、类固醇生成标志物及卵母细胞发育相关基因；并采用网络毒理学推断候选通路。PDE扰乱胎鼠卵巢形态发生，表现为生殖细胞巢提前破裂、增殖减少和凋亡增加。不同阶段、剂量和疗程的PDE均可增加卵巢类固醇合成（SF1、StAR、CYP11A1、Hsd3b、CYP19A1），同时抑制卵母细胞及卵泡发生相关基因（NOBOX、Figlα、Sohlh2、Bmp15、Gdf9）。这些效应具有阶段、剂量和疗程依赖性，其中妊娠中晚期暴露、高剂量及单疗程所致毒性最为明显。网络毒理学和qPCR揭示NR3C1-MAPK14-IL6轴：IL6与增殖及卵母细胞发育标志物呈正相关，而NR3C1/MAPK14与凋亡及类固醇生成相关。本研究为指导临床“精准医学”及有效评估胎鼠卵巢发育毒性风险提供了实验依据。
Abstract
Dexamethasone, a synthetic glucocorticoid, is widely used during pregnancy to prevent preterm infant respiratory distress syndrome. While our prior work established that multiple courses of prenatal dexamethasone exposure (PDE) impair offspring ovarian function with transgenerational effects, the specific impacts of exposure stages, doses, and courses remain poorly defined. Pregnant Kunming mice were treated with dexamethasone during mid-late gestation (GD14-15) or late gestation (GD16-17) with low/moderate/high doses, either as a single course or as two consecutive courses. Fetal ovaries were collected at GD18 to assess morphology, cell proliferation/apoptosis, steroidogenic markers, and oocyte-development genes; network toxicology was used to infer candidate pathways. PDE disrupted fetal ovarian morphogenesis, characterized by premature germ-cell nest breakdown, reduced proliferation and increased apoptosis. PDE at different stages, doses and courses can increase ovarian steroid synthesis (SF1\StAR\CYP11A1\Hsd3b\CYP19A1) while suppressing oocyte and folliculogenesis genes (NOBOX\Figlα\Sohlh2\Bmp15\Gdf9). These effects are stage-, dose- and course-dependent, with the most obvious toxicity resulting from exposure in the mid-late stages of pregnancy, at high doses and in a single course. Network toxicology and qPCR revealed the NR3C1-MAPK14-IL6 axis: IL6 was positively correlated with proliferation and oocyte development markers, while NR3C1/MAPK14 was associated with apoptosis and steroidogenesis. This study provides experimental evidence for guiding clinical "precision medicine" and effectively assessing the risk of fetal ovarian developmental toxicity.
如何引用
AMA
Lu Chen, Shan Jin, Zhaojun Wang, Abudukade Subinu, Fan Mo, Jing Huang, et al. Stage-, dose- and course-dependent disruption of mice fetal ovarian development following prenatal dexamethasone exposure.. Journal of ovarian research. 2026; doi:10.1186/s13048-026-02158-y.
APA
Lu Chen, Shan Jin, Zhaojun Wang, Abudukade Subinu, Fan Mo, Jing Huang, et al (2026). Stage-, dose- and course-dependent disruption of mice fetal ovarian development following prenatal dexamethasone exposure.. Journal of ovarian research. https://doi.org/10.1186/s13048-026-02158-y
GB/T 7714
Lu Chen, Shan Jin, Zhaojun Wang, Abudukade Subinu, Fan Mo, Jing Huang, et al. Stage-, dose- and course-dependent disruption of mice fetal ovarian development following prenatal dexamethasone exposure.[J]. Journal of ovarian research, 2026 doi:10.1186/s13048-026-02158-y.
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