Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

Niels E Skakkebaek, Ewa Rajpert-De Meyts, Germaine M Buck Louis, Jorma Toppari, Anna-Maria Andersson, Michael L Eisenberg, Tina Kold Jensen, Niels Jørgensen, Shanna H Swan, Katherine J Sapra, Søren Ziebe, Lærke Priskorn, Anders Juul

518 Citations (Scopus)


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.

Original languageEnglish
JournalPhysiological Reviews
Issue number1
Pages (from-to)55-97
Number of pages43
Publication statusPublished - Jan 2016


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