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Impaired spermatogenesis and associated endocrine effects of azole fungicides in peripubertal Xenopus tropicalis
Stockholm University, Faculty of Science, Department of Environmental Science.ORCID iD: 0000-0003-2795-9193
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Number of Authors: 62024 (English)In: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 270, article id 115876Article in journal (Refereed) Published
Abstract [en]

Early life exposure to endocrine disrupting chemicals (EDCs) has been suggested to adversely affect reproductive health in humans and wildlife. Here, we characterize endocrine and adverse effects on the reproductive system after juvenile exposure to propiconazole (PROP) or imazalil (IMZ), two common azole fungicides with complex endocrine modes of action. Using the frog Xenopus tropicalis, two short-term (2-weeks) studies were conducted. I: Juveniles (2 weeks post metamorphosis (PM)) were exposed to 0, 17 or 178 µg PROP/L. II: Juveniles (6 weeks PM) were exposed to 0, 1, 12 or 154 µg IMZ/L. Histological analysis of the gonads revealed an increase in the number of dark spermatogonial stem cells (SSCs)/testis area, and in the ratio secondary spermatogonia: dark SSCs were increased in all IMZ groups compared to control. Key genes in gametogenesis, retinoic acid and sex steroid pathways were also analysed in the gonads. Testicular levels of 3β-hsd, ddx4 were increased and cyp19 and id4 levels were decreased in the IMZ groups. In PROP exposed males, increased testicular aldh1a2 levels were detected, but no histological effects observed. Although no effects on ovarian histology were detected, ovarian levels of esr1, rsbn1 were increased in PROP groups, and esr1 levels were decreased in IMZ groups. In conclusion, juvenile azole exposure disrupted testicular expression of key genes in retinoic acid (PROP) and sex steroid pathways and in gametogenesis (IMZ). Our results further show that exposure to environmental concentrations of IMZ disrupted spermatogenesis in the juvenile testis, which is a cause for concern as it may lead to impaired fertility. Testicular levels of id4, ddx4 and the id4:ddx4 ratio were associated with the number of dark SSCs and secondary spermatogonia suggesting that they may serve as a molecular markers for disrupted spermatogenesis.

Place, publisher, year, edition, pages
2024. Vol. 270, article id 115876
Keywords [en]
Endocrine disruption, Spermatogenesis, Peripubertal, Azoles, Amphibians
National Category
Environmental Sciences Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:su:diva-227694DOI: 10.1016/j.ecoenv.2023.115876ISI: 001165780400001PubMedID: 38154155Scopus ID: 2-s2.0-85181734775OAI: oai:DiVA.org:su-227694DiVA, id: diva2:1849185
Available from: 2024-04-05 Created: 2024-04-05 Last updated: 2024-04-05Bibliographically approved

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Roza, MauricioKarlsson, Oskar

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