TY - JOUR

T1 - Possible fetal determinants of male infertility

AU - Juul, Anders

AU - Almstrup, Kristian

AU - Andersson, Anna-Maria

AU - Jensen, Tina K

AU - Jørgensen, Niels

AU - Main, Katharina M

AU - Rajpert-De Meyts, Ewa

AU - Toppari, Jorma

AU - Skakkebæk, Niels E

PY - 2014/9

Y1 - 2014/9

N2 - 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.

AB - 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.

KW - Animals

KW - Disorders of Sex Development

KW - Endocrine Disruptors

KW - Female

KW - Fetal Growth Retardation

KW - Humans

KW - Infertility, Male

KW - Klinefelter Syndrome

KW - Male

KW - Mothers

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Smoking

KW - Testicular Neoplasms

KW - Testis

KW - Testosterone

U2 - 10.1038/nrendo.2014.97

DO - 10.1038/nrendo.2014.97

M3 - Review

C2 - 24935122

VL - 10

SP - 553

EP - 562

JO - Nature Reviews Endocrinology

JF - Nature Reviews Endocrinology

SN - 1759-5029

IS - 9

ER -