Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

Research output: Contribution to journalJournal article – Annual report year: 2011Researchpeer-review

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Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. / Kristensen, David Møbjerg; Hass, Ulla; Lesné, Laurianne; Lottrup, Grete; Jacobsen, Pernille Rosenskjold; Desdoits-Lethimonier, Christele; Boberg, Julie; Petersen, Jørgen Holm; Toppari, Jorma; Jensen, Tina Kold; Brunak, Søren; Skakkebæk, Niels E.; Nellemann, Christine Lydia; Main, Katharina M.; Jégou, Bernard; Leffers, Henrik.

In: Human Reproduction, Vol. 26, No. 1, 2011, p. 235-244.

Research output: Contribution to journalJournal article – Annual report year: 2011Researchpeer-review

Harvard

Kristensen, DM, Hass, U, Lesné, L, Lottrup, G, Jacobsen, PR, Desdoits-Lethimonier, C, Boberg, J, Petersen, JH, Toppari, J, Jensen, TK, Brunak, S, Skakkebæk, NE, Nellemann, CL, Main, KM, 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

APA

CBE

Kristensen DM, Hass U, Lesné L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C, Boberg J, Petersen JH, Toppari J, Jensen TK, Brunak S, Skakkebæk NE, Nellemann CL, Main KM, 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. 26(1):235-244. https://doi.org/10.1093/humrep/deq323

MLA

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Author

Kristensen, David Møbjerg ; Hass, Ulla ; Lesné, Laurianne ; Lottrup, Grete ; Jacobsen, Pernille Rosenskjold ; Desdoits-Lethimonier, Christele ; Boberg, Julie ; Petersen, Jørgen Holm ; Toppari, Jorma ; Jensen, Tina Kold ; Brunak, Søren ; Skakkebæk, Niels E. ; Nellemann, Christine Lydia ; Main, Katharina M. ; Jégou, Bernard ; Leffers, Henrik. / Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. In: Human Reproduction. 2011 ; Vol. 26, No. 1. pp. 235-244.

Bibtex

@article{ee85ee8563714252a87cdc1122d726e1,
title = "Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat",
abstract = "; 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.",
keywords = "Andrology, Testosterone, Testis, Environmental effects, Animal model",
author = "Kristensen, {David M{\o}bjerg} and Ulla Hass and Laurianne Lesn{\'e} and Grete Lottrup and Jacobsen, {Pernille Rosenskjold} and Christele Desdoits-Lethimonier and Julie Boberg and Petersen, {J{\o}rgen Holm} and Jorma Toppari and Jensen, {Tina Kold} and S{\o}ren Brunak and Skakkeb{\ae}k, {Niels E.} and Nellemann, {Christine Lydia} and Main, {Katharina M.} and Bernard J{\'e}gou and Henrik Leffers",
year = "2011",
doi = "10.1093/humrep/deq323",
language = "English",
volume = "26",
pages = "235--244",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

AU - Kristensen, David Møbjerg

AU - Hass, Ulla

AU - Lesné, Laurianne

AU - Lottrup, Grete

AU - Jacobsen, Pernille Rosenskjold

AU - Desdoits-Lethimonier, Christele

AU - Boberg, Julie

AU - Petersen, Jørgen Holm

AU - Toppari, Jorma

AU - Jensen, Tina Kold

AU - Brunak, Søren

AU - Skakkebæk, Niels E.

AU - Nellemann, Christine Lydia

AU - Main, Katharina M.

AU - Jégou, Bernard

AU - Leffers, Henrik

PY - 2011

Y1 - 2011

N2 - ; 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.

AB - ; 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.

KW - Andrology

KW - Testosterone

KW - Testis

KW - Environmental effects

KW - Animal model

U2 - 10.1093/humrep/deq323

DO - 10.1093/humrep/deq323

M3 - Journal article

VL - 26

SP - 235

EP - 244

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 1

ER -