title: Possible fetal determinants of male infertility.
abstract: Although common reproductive problems, such as male infertility and testicular cancer, present in adult life, strong evidence exists that these reproductive disorders might have a fetal origin. The evidence is derived not only from large epidemiological studies that show birth-cohort effects with regard to testicular cancer, levels of testosterone and semen quality, but also from histopathological observations. Many infertile men have histological signs of testicular dysgenesis, including Sertoli-cell-only tubules, immature undifferentiated Sertoli cells, microliths and Leydig cell nodules. The most severe gonadal symptoms occur in patients with disorders of sexual development (DSDs) who have genetic mutations, in whom even sex reversal of individuals with a 46,XY DSD can occur. However, patients with severe DSDs might represent only a small proportion of DSD cases, with milder forms of testicular dysgenesis potentially induced by exposure to environmental and lifestyle factors. Interestingly, maternal smoking during pregnancy has a stronger effect on spermatogenesis than a man's own smoking. Other lifestyle factors such as alcohol consumption and obesity might also have a role. However, increasing indirect evidence exists that exposure to ubiquitous endocrine disrupting chemicals, present at measurable concentrations in individuals, might affect development of human fetal testis. If confirmed, health policies to prevent male reproductive problems should not only target adult men, but also pregnant women and their children.
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Almstrup
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Andersson
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Tina K
authors.initials: TK
authors.lastname: Jensen
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jørgensen
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Niels E
authors.initials: NE
authors.lastname: Skakkebæk
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development / Q000150:complications; D052244:Endocrine Disruptors / Q000009:adverse effects; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D006801:Humans; D007248:Infertility, Male / Q000209:etiology*; D007713:Klinefelter Syndrome / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking / Q000009:adverse effects; D013736:Testicular Neoplasms / Q000196:embryology; D013737:Testis / Q000002:abnormalities / Q000196:embryology; D013739:Testosterone / Q000097:blood
chemical_list: D052244:Endocrine Disruptors; D013739:Testosterone