Combined developmental exposure to estrogenic endocrine disruptor and nutritional imbalance induces long term adult prostate inflammation through inflammasome activation.

Autor: Gharieb K; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Doumandji N; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Bensalem W; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Bellon RP; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Inoubli L; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Siddeek B; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Traverse-Glehen A; Université Lyon 1, UFR Médecine Lyon Sud, Lyon F-69921, France; Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d'Anatomie et de Cytologie Pathologiques, Pierre-Bénite F-69495, France., Decaussin-Petrucci M; Université Lyon 1, UFR Médecine Lyon Sud, Lyon F-69921, France; Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d'Anatomie et de Cytologie Pathologiques, Pierre-Bénite F-69495, France., Trabucchi M; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Benahmed M; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France., Mauduit C; Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France; Université Lyon 1, UFR Médecine Lyon Sud, Lyon F-69921, France; Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d'Anatomie et de Cytologie Pathologiques, Pierre-Bénite F-69495, France. Electronic address: claire.mauduit@univ-lyon1.fr.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2024 Dec; Vol. 402, pp. 1-14. Date of Electronic Publication: 2024 Oct 03.
DOI: 10.1016/j.toxlet.2024.10.001
Abstrakt: Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1-5, or to a combination of both. EB and EB+HFD exposures induced decreased prostate weight in adult rats along with inflammatory status. A white blood cell infiltrate was observed after EB exposure and more dramatic lesions were observed with the combined exposure, along with a gland destruction. The lesions, following EB or EB+HFD exposure, are associated with elevated mRNA levels for TNFa, IL6 and CCL2/MCP1 pro-inflammatory cytokines while the levels of the anti-inflammatory IL10 cytokine remained unchanged. This activation of NLRP3 and elevated levels of CASP1 were observed following EB or EB+HFD exposures associated with elevated mRNA levels for IL1b, substrates for the NLRP3 complex. HFD exposure alone has mild if not pro-inflammatory effects in adult prostate. In conclusion, we showed that developmental combined exposure to EB and HFD programmed prostate inflammatory lesions in adult prostate. Since proliferative inflammatory atrophy and chronic inflammation of prostate may drive cell to become cancer cells, our model might be useful for study onset of PCa.
Competing Interests: Declaration of Competing Interest The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BASF Agro (CIFRE doctoral grant), CEFIC-LRI and BASF Agro (fellowships).
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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