Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

David Møbjerg Kristensen; Christèle Desdoits-Lethimonier; Abigail L Mackey; Marlene Danner Dalgaard; Federico De Masi; Cecilie Hurup Munkbøl; Bjarne Styrishave; Jean-Philippe Antignac; Bruno Le Bizec; Christian Platel; Anders Hay-Schmidt; Tina Kold Jensen; Laurianne Lesné; Séverine Mazaud-Guittot; Karsten Kristiansen; Søren Brunak; Michael Kjaer; Anders Juul; Bernard Jégou

doi:10.1073/pnas.1715035115

Lifestyle and Environment · Environmental Exposures

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

Kristensen DM, Desdoits-Lethimonier C, Mackey AL, Dalgaard MD, De Masi F, Munkbøl CH, Styrishave B, Antignac JP, Le Bizec B, Platel C, Hay-Schmidt A, Jensen TK, Lesné L, Mazaud-Guittot S, Kristiansen K, Brunak S, Kjaer M, Juul A, Jégou B

Published January 23, 2018 Proceedings of the National Academy of Sciences of the United States of America, 115(4), E715-E724

DOI 10.1073/pnas.1715035115 PMID 29311296 PMC PMC5789927

Abstract

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

Topics

Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals · Male Fertility › Male Endocrine and Genetic Factors › Male Hormonal Axis

David Møbjerg Kristensen, Christèle Desdoits-Lethimonier, Abigail L Mackey, Marlene Danner Dalgaard, Federico De Masi, Cecilie Hurup Munkbøl, Bjarne Styrishave, Jean-Philippe Antignac, Bruno Le Bizec, Christian Platel, Anders Hay-Schmidt, Tina Kold Jensen, Laurianne Lesné, Séverine Mazaud-Guittot, Karsten Kristiansen, Søren Brunak, Michael Kjaer, Anders Juul, Bernard Jégou

Dave Kristensen, D Kristensen, C Desdoits-Lethimonier, Abby Mackey, A Mackey, M Dalgaard, F Masi, C Munkbøl, B Styrishave, J Antignac, B Bizec, C Platel, A Hay-Schmidt, T Jensen, L Lesné, S Mazaud-Guittot, K Kristiansen, S Brunak, Mike Kjaer, M Kjaer, A Juul, B Jégou

PMID 29311296 29311296 DOI 10.1073/pnas.1715035115 10.1073/pnas.1715035115 Kristensen et al. 2018, Kristensen 2018

Keywords

Adult, Analgesics, Non-Narcotic/adverse Effects/blood, Cell Line, Gene Expression/drug Effects, Humans, Hypogonadism/blood/chemically Induced, Ibuprofen/adverse Effects/blood, In Vitro Techniques, Leydig Cells/drug Effects/metabolism, Luteinizing Hormone/blood, Male, Middle Aged, Prostaglandins/biosynthesis, Sertoli Cells/drug Effects, Testosterone/blood, Analgesics, Non-Narcotic, Prostaglandins, Testosterone, Luteinizing Hormone, Ibuprofen, Endocrine Disruption, Endocrinology, Hypogonadism, Ibuprofen, Reproduction

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

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