PMID- 37995777 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20240102 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 387 DP - 2024 Jan 5 TI - A "toxic window" study on the hippocampal development of mice offspring exposed to azithromycin at different doses, courses, and time during pregnancy. PG - 110814 LID - S0009-2797(23)00481-7 [pii] LID - 10.1016/j.cbi.2023.110814 [doi] AB - BACKGROUND: Azithromycin, one of the new-generation macrolides, is an effective medicine for the treatment of mycoplasma infection during pregnancy. Epidemiological studies have reported adverse pregnancy outcomes with prenatal azithromycin exposure (PAzE). However, the effect of PAzE on fetal hippocampal development is unclear. This study aimed to explore the effects and potential mechanism of PAzE-induced fetal hippocampal development at different doses, courses, and time. METHOD: Pregnant mice were administered azithromycin by gavage at different doses (50, 100 or 200 mg/kg.d), different courses (gestational day (GD)15-17 for three consecutive days, or GD17 once a day) and different time (GD10-12, GD15-17). RESULTS: Compared with the control group, morphological development damage of the fetal hippocampus was observed in the PAzE group, with a dysbalance in neuronal proliferation and apoptosis, decreased expression of the neuronal-specific marker Snap25, NeuN, PSD95 and Map2, increased expression of the glial-specific marker Iba1, GFAP, and S-100beta, and decreased expression of P2ry12. The PAzE-induced hippocampal developmental deficiency varied based on different doses, courses, and time, and the developmental toxicity was most significant in the late pregnancy, high dose, multi-course group (AZHT). The significant reduction of SOX2 and Wnt, which were related to regulation of neural progenitor cells (NPCs) proliferation in PAzE fetus compared with the control group indicated that the SOX2/Wnt signaling may be involved in PAzE-induced hippocampal developmental toxicity. CONCLUSION: In this study, PAzE was associated with hippocampal developmental toxicity in a variety of nerve cells. Hippocampal developmental toxicity due to azithromycin was most significant in the late pregnancy, high-dose (equivalent to maximum clinical dose) and multi-course group (AZHT). The findings provide an experimental and theoretical foundation for guiding the sensible use of medications during pregnancy and effectively assessing the risk of fetal hippocampal developmental toxicity. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Wei, Liyi AU - Wei L AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Wang, Tingting AU - Wang T AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Luo, Mingcui AU - Luo M AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Zhang, Shuai AU - Zhang S AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Lu, Mengxi AU - Lu M AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Zhou, Xinli AU - Zhou X AD - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Cheng, Xuelei AU - Cheng X AD - Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China. FAU - Wang, Hui AU - Wang H AD - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Xu, Dan AU - Xu D AD - Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. Electronic address: xuyidan70188@whu.edu.cn. LA - eng PT - Journal Article DEP - 20231121 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 83905-01-5 (Azithromycin) SB - IM MH - Female MH - Humans MH - Pregnancy MH - Animals MH - Mice MH - *Prenatal Exposure Delayed Effects/chemically induced MH - Azithromycin/toxicity MH - Fetus MH - Neurons MH - Hippocampus OTO - NOTNLM OT - Azithromycin OT - Hippocampus OT - Medication during pregnancy OT - Neurodevelopment OT - Toxicity COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/24 00:42 MHDA- 2023/12/25 06:42 CRDT- 2023/11/23 19:26 PHST- 2023/03/21 00:00 [received] PHST- 2023/11/07 00:00 [revised] PHST- 2023/11/15 00:00 [accepted] PHST- 2023/12/25 06:42 [medline] PHST- 2023/11/24 00:42 [pubmed] PHST- 2023/11/23 19:26 [entrez] AID - S0009-2797(23)00481-7 [pii] AID - 10.1016/j.cbi.2023.110814 [doi] PST - ppublish SO - Chem Biol Interact. 2024 Jan 5;387:110814. doi: 10.1016/j.cbi.2023.110814. Epub 2023 Nov 21.