TY - JOUR

T1 - Male Reproductive Disorders and Fertility Trends

T2 - Influences of Environment and Genetic Susceptibility

AU - Skakkebaek, Niels E

AU - Rajpert-De Meyts, Ewa

AU - Buck Louis, Germaine M

AU - Toppari, Jorma

AU - Andersson, Anna-Maria

AU - Eisenberg, Michael L

AU - Jensen, Tina Kold

AU - Jørgensen, Niels

AU - Swan, Shanna H

AU - Sapra, Katherine J

AU - Ziebe, Søren

AU - Priskorn, Lærke

AU - Juul, Anders

N1 - Copyright © 2016 the American Physiological Society.

PY - 2016/1

Y1 - 2016/1

N2 - It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

AB - It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

KW - Environmental Exposure

KW - Fertility

KW - Gene-Environment Interaction

KW - Genetic Predisposition to Disease

KW - Humans

KW - Incidence

KW - Infertility, Male

KW - Life Style

KW - Male

KW - Phenotype

KW - Population Dynamics

KW - Risk Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1152/physrev.00017.2015

DO - 10.1152/physrev.00017.2015

M3 - Review

C2 - 26582516

VL - 96

SP - 55

EP - 97

JO - Physiological Reviews

JF - Physiological Reviews

SN - 0031-9333

IS - 1

ER -