Toxic effects of prenatal azithromycin exposure on fetal adrenal gland in mice: The role of stage, dose and course of treatment

IF 3.4 3区医学 Q2 PHARMACOLOGY & PHARMACY Toxicology and applied pharmacology Pub Date : 2025-01-29 DOI:10.1016/j.taap.2025.117244

Xiaomin Li , Ying Xiong , Aihemaitijiang Ailikaiti , Ying Ao , Hao Kou , Hui Wang

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Abstract

Azithromycin is widely used in treating bacterial infections during pregnancy. Previous studies suggest prenatal exposure (PAzE) induces embryonic developmental toxicity. However, the influence of PAzE on fetal adrenal gland development is unknown. Pregnant mice received azithromycin in varying ways: different stages (mid- and late-pregnancy), doses (50, 100, and 200 mg/kg d), and courses (single- and multi-course). Adrenal gland morphology, cell proliferation, apoptosis, steroid synthesis, and expression of key transcriptional factors were examined. PAzE predominantly affected fetal adrenal gland development in males, characterized by obvious pathological changes (irregular arrangement and decreased density of adrenocortical cells, aggravated cytoplasmic vacuolization), weakened cell proliferation (decreased Pcna but increased Caspase3 expression), and inhibited steroidogenesis (reduced expression of Star, 3β-hsd, P450c21, and P450c11). The most significant damage occurred with multi-course high-dose (clinical dose) azithromycin treatment in late-pregnancy, possibly linked to inhibited Cited2 expression. This study delineated the sex-specific toxic effects of PAzE on fetal adrenal gland development, influenced by various stages, doses, and courses of azithromycin treatment. These findings contribute to a better understanding of azithromycin's safe use during pregnancy and offer a crucial theoretical and experimental foundation for future research.

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产前阿奇霉素暴露对小鼠胎儿肾上腺的毒性作用：治疗阶段、剂量和疗程的作用。

阿奇霉素广泛用于治疗妊娠期细菌感染。先前的研究表明，产前暴露（PAzE）可诱导胚胎发育毒性。然而，PAzE对胎儿肾上腺发育的影响尚不清楚。妊娠小鼠以不同方式接受阿奇霉素：不同阶段（妊娠中期和妊娠晚期）、剂量（50、100和200 mg/kg d）和疗程（单疗程和多疗程）。检测肾上腺形态、细胞增殖、凋亡、类固醇合成和关键转录因子的表达。PAzE主要影响雄性胎儿肾上腺发育，表现为明显的病理改变（肾上腺皮质细胞排列不规则，密度降低，细胞质空泡化加剧），细胞增殖减弱（Pcna减少，Caspase3表达增加），抑制甾体生成（Star、3β-hsd、P450c21、P450c11表达减少）。最显著的损伤发生在妊娠后期多疗程高剂量（临床剂量）阿奇霉素治疗中，可能与抑制Cited2表达有关。这项研究描述了PAzE对胎儿肾上腺发育的性别特异性毒性作用，受阿奇霉素治疗的不同阶段、剂量和疗程的影响。这些发现有助于更好地了解阿奇霉素在妊娠期间的安全使用，并为今后的研究提供重要的理论和实验基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.