阿奇霉素,一种常用的大环内酯类抗生素,用于治疗怀孕期间的衣原体感染,引发了对其对后代发育的潜在影响的研究。尽管有这些询问,产前阿奇霉素暴露(PAzE)对后代卵巢发育的具体影响以及确切的“效应窗口”仍存在不确定性。怀孕的老鼠,遵循阿奇霉素给药的临床指南,在不同的妊娠阶段口服阿奇霉素[(妊娠日,GD)10-12或GD15-17],剂量(50、100或200mg/kg·d),和课程(单个或多个)。在GD18上,我们收集了后代的血液和卵巢,以检查胎儿血清雌二醇(E2)水平的变化,胎儿卵巢形态学,前颗粒细胞功能,和卵母细胞发育。PAzE的多个疗程导致胎儿卵巢形态发育异常,杂乱无章的生殖细胞巢,增强卵巢细胞增殖,减少细胞凋亡。同时,多个疗程的PAZE显着增加胎儿血清E2水平,卵巢类固醇生成功能升高(由Star表示,3β-hsd,和Cyp19表达式),卵母细胞发育中断(由图1α和Nobox表达表示),并导致胎儿卵巢中MAPK信号通路的改变,特别是在高剂量治疗组中。相比之下,单疗程PAZE减少胎儿卵巢细胞增殖,类固醇生成功能降低,抑制卵母细胞发育,特别是通过下调MAPK信号通路中Mek2的表达。这些发现表明PAzE可以影响胎儿小鼠卵巢细胞发育的各个方面。多疗程增强前颗粒细胞雌激素合成功能,促进生殖细胞发育,而单一的终末妊娠剂量抑制生殖细胞发育。这些差异效应可能与MAPK信号通路的变化有关。
Azithromycin, a commonly used macrolide antibiotic for treating chlamydial infections during pregnancy, has sparked investigations into its potential effects on offspring development. Despite these inquiries, there remains uncertainty about the specific impact of prenatal azithromycin exposure (PAzE) on offspring ovarian development and the precise \"effect window\". Pregnant mice, following clinical guidelines for azithromycin dosing, were orally administered azithromycin at different gestational stages [(gestational day, GD) 10-12 or GD 15-17], doses (50, 100, or 200 mg/kg·d), and courses (single or multiple). On GD 18, we collected offspring blood and ovaries to examine changes in fetal serum estradiol (E2) levels, fetal ovarian morphology, pre-granulosa cell function, and oocyte development. Multiple courses of PAzE resulted in abnormal fetal ovarian morphological development, disorganized germ cell nests, enhanced ovarian cell proliferation, and reduced apoptosis. Simultaneously, multiple courses of PAzE significantly increased fetal serum E2 levels, elevated ovarian steroidogenic function (indicated by Star, 3β-hsd, and Cyp19 expression), disrupted oocyte development (indicated by Figlα and Nobox expression), and led to alterations in the MAPK signal pathway in fetal ovaries, particularly in the high-dose treatment group. In contrast, a single course of PAzE reduced fetal ovarian cell proliferation, decreased steroidogenic function, and inhibited oocyte development, particularly through the downregulation of Mek2 expression in the MAPK signal pathway. These findings suggest that PAzE can influence various aspects of fetal mouse ovarian cell development. Multiple courses enhance pre-granulosa cell estrogen synthesis function and advance germ cell development, while a single terminal gestation dose inhibits germ cell development. These differential effects may be associated with changes in the MAPK signal pathway.