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
SN - 1759-5029
VL - 10
SP - 553
EP - 562
JO - Nature Reviews Endocrinology
JF - Nature Reviews Endocrinology
IS - 9
ER -
