{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:20:05Z","timestamp":1790961605048,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Electronic cigarettes (e-cigarettes) have gained widespread diffusion as a perceived safer alternative to conventional smoking, particularly among women of reproductive age. The present systematic review provides an overview of the current literature on the effects of e-cigarette exposure on female reproductive function, embryonic development, and pregnancy outcomes, with a focus on underlying molecular mechanisms. A systematic literature search was conducted in PubMed, Web of Science, and Google Scholar, and the review was conducted in accordance with the PRISMA 2020 guidelines. A total of 11 studies met the eligibility criteria and were included in the qualitative synthesis, comprising six experimental and five clinical studies. Experimental studies suggest that e-cigarette exposure may impair ovarian function, leading to morphological alterations, disrupted folliculogenesis, and altered steroidogenesis, mainly through oxidative stress, apoptosis, mitochondrial dysfunction, and dysregulation of pathways such as Hippo signaling. Non-nicotine components, including propylene glycol (PG), vegetable glycerin (VG), and flavoring agents, appear to be key contributors. Adverse effects on implantation, embryo development, and placental growth have also been reported in experimental models, although further studies are needed. Clinical evidence remains scarce, suggesting possible associations between e-cigarette smoking and reduced ovarian reserve and fecundability in naturally conceiving women. No conclusive associations have been identified with in vitro fertilization outcomes. Overall, e-cigarette exposure may negatively affect female reproductive function, although the predominance of experimental data and the limited clinical evidence preclude definitive conclusions.<\/jats:p>","DOI":"10.3390\/ijms27146528","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"6528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electronic Cigarettes and Female Reproduction: A Systematic Review of Experimental and Clinical Evidence"],"prefix":"10.3390","volume":"27","author":[{"given":"Maria Cristina","family":"Budani","sequence":"first","affiliation":[{"name":"School of Medicine and Health Sciences, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-5230","authenticated-orcid":false,"given":"Gian Mario","family":"Tiboni","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via Dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2021). Vital Strategies. The Tobacco Atlas, American Cancer Society. [6th ed.]. Available online: https:\/\/tobaccoatlas.org."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/humupd\/dmq033","article-title":"Effects of cigarette smoking on reproduction","volume":"17","author":"Dechanet","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.reprotox.2017.06.184","article-title":"Ovotoxicity of cigarette smoke: A review of the literature","volume":"72","author":"Budani","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.reprotox.2018.06.001","article-title":"Cigarette smoking impairs clinical outcomes of assisted reproductive technologies: A meta-analysis of the literature","volume":"80","author":"Budani","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1017\/S0967199417000132","article-title":"Cigarette smoke is associated with altered expression of antioxidant enzymes in granulosa cells from women undergoing in vitro fertilization","volume":"25","author":"Budani","year":"2017","journal-title":"Zygote"},{"key":"ref_6","first-page":"30","article-title":"Effects of electronic cigarettes on health: A systematic review of the available evidence","volume":"111","author":"Amato","year":"2020","journal-title":"Recenti Prog. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ypmed.2014.10.009","article-title":"A systematic review of health effects of electronic cigarettes","volume":"69","author":"Pisinger","year":"2014","journal-title":"Prev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_9","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2026, July 02). The Newcastle\u2013Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analysis. Available online: http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00404-025-08066-8","article-title":"The impact of electronic cigarettes on pregnancy and childhood health outcomes: The ECHO study\u2014A protocol for a multicentre, prospective, observational cohort","volume":"312","author":"Healy","year":"2025","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ammar, L., Tindle, H.A., Miller, A.M., Adgent, M.A., Nian, H., Ryckman, K.K., Mogos, M., Piano, M.R., Xie, E., and Snyder, B.M. (2023). Electronic cigarette use during pregnancy and the risk of adverse birth outcomes: A cross-sectional surveillance study of the US Pregnancy Risk Assessment Monitoring System (PRAMS) population. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0287348"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1089\/jwh.2019.8075","article-title":"Biomarkers of toxicant exposure and inflammation among women of reproductive age who use electronic or conventional cigarettes","volume":"30","author":"Perez","year":"2021","journal-title":"J. Womens Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36","DOI":"10.18332\/tid\/146958","article-title":"Effect of e-cigarette refill liquid on follicular development and estrogen secretion in rats","volume":"20","author":"Chen","year":"2022","journal-title":"Tob. Induc. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.18332\/tid\/170631","article-title":"Ovarian toxicity of e-cigarette liquids: Effects of components and high and low nicotine concentration e-cigarette liquid In Vitro","volume":"21","author":"Chen","year":"2023","journal-title":"Tob. Induc. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ashour, A., Alhussain, H., Rashid, U.B., Abughazzah, L., Gupta, I., Malki, A., Vranic, S., and Al Moustafa, A.E. (2020). E-cigarette liquid provokes significant embryotoxicity and inhibits angiogenesis. Toxics, 8.","DOI":"10.3390\/toxics8020038"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kennedy, A.E., Kandalam, S., Olivares-Navarrete, R., and Dickinson, A.J.G. (2017). E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185729"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1210\/js.2019-00216","article-title":"E-cigarette exposure delays implantation and causes reduced weight gain in female offspring exposed in utero","volume":"3","author":"Wetendorf","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s43856-025-01094-0","article-title":"Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine","volume":"5","author":"Marbrey","year":"2025","journal-title":"Commun. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/aje\/kwaa067","article-title":"Electronic cigarettes and fecundability: Results from a prospective preconception cohort study","volume":"190","author":"Harlow","year":"2021","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wainwright, E., Dhonnabh\u00e1in, B.N., Vaz, S.R., Vasavan, T., Getreu, N., and O\u2019Neill, H.C. (2024). Vaping and smoking significantly reduce ovarian reserve markers: A retrospective cohort study of 21,102 women. Authorea, preprints.","DOI":"10.22541\/au.173115715.52177098\/v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9597","DOI":"10.1038\/s41598-024-60251-y","article-title":"Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment","volume":"14","author":"Trapphoff","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_22","first-page":"5190","article-title":"Impact of different typologies of smoking on ovarian reserve and oocyte quality in women performing ICSI cycles: An observational prospective study","volume":"27","author":"Galanti","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23714","DOI":"10.1038\/s41598-025-09495-w","article-title":"Impact of conventional cigarette and electronic cigarette use on sperm quality and IVF\/ICSI outcomes","volume":"15","author":"Kim","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1159\/000353253","article-title":"Electronic cigarettes: A short review","volume":"86","author":"Bertholon","year":"2013","journal-title":"Respiration"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Montjean, D., Godin Pag\u00e9, M.H., B\u00e9langer, M.C., Benkhalifa, M., and Miron, P. (2023). An overview of e-cigarette impact on reproductive health. Life, 13.","DOI":"10.3390\/life13030827"},{"key":"ref_26","first-page":"17","article-title":"Respiratory impact of electronic cigarettes and \u201clow-risk\u201d tobacco","volume":"71","author":"Zabert","year":"2019","journal-title":"Rev. Investig. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1093\/ntr\/ntu078","article-title":"Carbonyl compounds in electronic cigarette vapors: Effects of nicotine solvent and battery output voltage","volume":"16","author":"Kosmider","year":"2014","journal-title":"Nicotine Tob. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s00204-014-1294-7","article-title":"Chemical hazards present in liquids and vapors of electronic cigarettes","volume":"88","author":"Hutzler","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/ntr\/nts103","article-title":"Nicotine levels in electronic cigarettes","volume":"15","author":"Goniewicz","year":"2012","journal-title":"Nicotine Tob. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.chroma.2013.03.035","article-title":"Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography\u2013tandem mass spectrometry","volume":"1291","author":"Kim","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3109\/10408449109017917","article-title":"Nicotine-derived N-nitrosamines (TSNA) and their relevance in tobacco carcinogenesis","volume":"21","author":"Hoffmann","year":"1991","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1111\/add.12235","article-title":"Analysis of refill liquids for electronic cigarettes","volume":"108","author":"Etter","year":"2013","journal-title":"Addiction"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/ntr\/ntv189","article-title":"Levels of selected groups of compounds in refill solutions for electronic cigarettes","volume":"18","author":"Han","year":"2015","journal-title":"Nicotine Tob. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhu, M., Xu, M., Zhang, J., and Zheng, C. (2023). The role of Hippo pathway in ovarian development. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1198873"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17474","DOI":"10.1073\/pnas.1312830110","article-title":"Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment","volume":"110","author":"Kawamura","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.rbmo.2017.03.008","article-title":"Ovarian tissue cryopreservation in female-to-male transgender people: Insights into ovarian histology and physiology after prolonged androgen treatment","volume":"34","author":"Lierman","year":"2017","journal-title":"Reprod. Biomed. 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