Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China.
Life Sci. 2023 Sep 15;329:121985. doi: 10.1016/j.lfs.2023.121985. Epub 2023 Jul 27.
Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an "emerging pollutant", is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE.
We focused on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice at different doses (50/200 mg/kg·d) during late pregnancy or at 200 mg/kg·d during different stages (mid-/late-pregnancy) and courses (single-/multi-course).
The results showed PAzE increased the rate of the absorbed fetus during mid-pregnancy and increased the intrauterine growth retardation rate (IUGR) during late pregnancy. PAzE caused multiple blood phenotypic changes in maternal and fetal mice, among which the number and degree of changes in fetal blood indicators were more significant. Moreover, PAzE inhibited long bone/cartilage development and adrenal steroid synthesis, promoting hepatic lipid production and ovarian steroid synthesis in varying degrees. The order of severity might be bone/cartilage > liver > gonads > other organs. PAzE-induced multi-organ alterations differed in stages, courses doses and fetal sex. The most apparent changes might be in high-dose, mid-pregnancy, multi-course, and female, while there was no typical rule for a dose-response relationship.
This study confirmed PAzE could cause fetal developmental abnormalities and multi-organ functional alterations, which deepens the comprehensive understanding of azithromycin's fetal developmental toxicity.
阿奇霉素在临床实践中被广泛用于治疗孕妇感染。同时，由于阿奇霉素的使用量迅速增加（尤其是在 COVID-19 之后），作为一种“新兴污染物”，它对环境的污染也越来越严重。先前的研究表明，产前接触阿奇霉素（PAzE）可能存在致畸风险，但它对胎儿多器官发育的影响尚不清楚。本研究旨在探讨 PAzE 的潜在影响。
我们重点研究了不同剂量（50/200mg/kg·d）在妊娠晚期或 200mg/kg·d 在不同阶段（中-晚期）和疗程（单次/多次）时对妊娠结局、母胎血清表型和胎儿多器官发育的影响。
结果表明，PAzE 增加了中孕期胎儿吸收率，并增加了晚孕期宫内生长迟缓率（IUGR）。PAzE 导致母鼠和胎鼠的多种血液表型发生变化，其中胎鼠血液指标的数量和变化程度更为显著。此外，PAzE 抑制长骨/软骨发育和肾上腺类固醇合成，在不同程度上促进肝脂生成和卵巢类固醇合成。严重程度的顺序可能是骨/软骨>肝>性腺>其他器官。PAzE 引起的多器官改变在阶段、疗程、剂量和胎儿性别上存在差异。最明显的变化可能发生在高剂量、中孕期、多次疗程和雌性中，而剂量反应关系没有典型规律。
本研究证实 PAzE 可导致胎儿发育异常和多器官功能改变，加深了对阿奇霉素胎儿发育毒性的全面认识。
