Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat
| Autor: | Pernille Rosenskjold Jacobsen, Niels E. Skakkebæk, Christine Nellemann, David Møbjerg Kristensen, Jorma Toppari, Jørgen Holm Petersen, Ulla Hass, Tina Kold Jensen, Henrik Leffers, Bernard Jégou, Katharina M. Main, Julie Boberg, Laurianne Lesné, Christèle Desdoits-Lethimonier, Grete Lottrup, Søren Brunak |
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| Přispěvatelé: | Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Department of Environmental Medicine, University of Southern Denmark (SDU)-Institute of Public Health, the European Commission (EU-F7 grant # 212844 and 212502), the Villum Kann Rasmussen Foundation, the Novo Nordisk Foundation, Inserm (Institut National de la Santé et de la Recherche Médicale), Ministère de l'Enseignement Supérieur et de la Recherche, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
MESH: Analgesics Environmental effects environmental effects Ibuprofen andrology Male infertility Cohort Studies 0302 clinical medicine MESH: Pregnancy Pregnancy Risk Factors MESH: Risk Factors Testis Cryptorchidism Testosterone MESH: Animals Andrology MESH: Cohort Studies 0303 health sciences Analgesics 030219 obstetrics & reproductive medicine Obstetrics Rehabilitation Anogenital distance Obstetrics and Gynecology MESH: Ibuprofen 3. Good health Prenatal Exposure Delayed Effects Gestation Female Cohort study Infertility medicine.medical_specialty MESH: Rats MESH: Acetaminophen testis MESH: Infertility Male MESH: Prenatal Exposure Delayed Effects 03 medical and health sciences MESH: Cryptorchidism medicine Endocrine system Animals Humans Animal model Risk factor MESH: Aspirin Infertility Male 030304 developmental biology Acetaminophen Gynecology MESH: Humans Aspirin business.industry animal model [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology medicine.disease MESH: Male Rats Reproductive Medicine testosterone business MESH: Female |
| Zdroj: | Human Reproduction Human Reproduction, Oxford University Press (OUP), 2011, 26 (1), pp.235-44. ⟨10.1093/humrep/deq323⟩ Kristensen, D M B, Hass, U, Lesné, L, Lottrup, G, Jacobsen, P R, Desdoits-Lethimonier, C, Boberg, J, Petersen, J H, Toppari, J, Jensen, T K, Brunak, S, Skakkebaek, N E, Nellemann, C L, Main, K M, Jégou, B & Leffers, H 2011, ' Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat ', Human Reproduction, vol. 26, no. 1, pp. 235-44 . https://doi.org/10.1093/humrep/deq323 Human Reproduction, 2011, 26 (1), pp.235-44. ⟨10.1093/humrep/deq323⟩ Kristensen, D M, Hass, U, Lesné, L, Lottrup, G, Jacobsen, P R, Desdoits-Lethimonier, C, Boberg, J, Petersen, J H, Toppari, J, Jensen, T K, Brunak, S, Skakkebæk, N E, Nellemann, C L, Main, K M, Jégou, B & Leffers, H 2011, ' Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat ', Human Reproduction, vol. 26, no. 1, pp. 235-244 . https://doi.org/10.1093/humrep/deq323 |
| ISSN: | 0268-1161 1460-2350 |
| DOI: | 10.1093/humrep/deq323⟩ |
| Popis: | International audience; BACKGROUND: More than half of pregnant women in the Western world report intake of mild analgesics, and some of these drugs have been associated with anti-androgenic effects in animal experiments. Intrauterine exposure to anti-androgens is suspected to contribute to the recent increase in male reproductive problems, and many of the anti-androgenic compounds are like the mild analgesics potent inhibitors of prostaglandin synthesis. Therefore, it appears imperative to further investigate the potential endocrine disrupting properties of mild analgesics. METHODS: In a prospective birth cohort study, 2297 Danish and Finnish pregnant women completed a questionnaire and 491 of the Danish mothers participated in a telephone interview, reporting on their use of mild analgesics during pregnancy. The testicular position of newborns was assessed by trained paediatricians. In rats, the impact of mild analgesics on anogenital distance (AGD) after intrauterine exposure was examined together with the effect on ex vivo gestational day 14.5 testes. RESULTS: In the Danish birth cohort, the use of mild analgesics was dose-dependently associated with congenital cryptorchidism. In particular, use during the second trimester increased the risk. This risk was further increased after the simultaneous use of different analgesics. The association was not found in the Finnish birth cohort. Intrauterine exposure of rats to paracetamol led to a reduction in the AGD and mild analgesics accordingly reduced testosterone production in ex vivo fetal rat testes. CONCLUSION: There was an association between the timing and the duration of mild analgesic use during pregnancy and the risk of cryptorchidism. These findings were supported by anti-androgenic effects in rat models leading to impaired masculinization. Our results suggest that intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders. |
| Databáze: | OpenAIRE |
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