Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): Environmental connection

Abstract

Cryptorchidism and hypospadias are common genital birth defects that affect 2-9% and 0.2-1% of male newborns, respectively. The incidence of both defects shows large geographic variation, and in several countries increasing trends have been reported. The conditions share many risk factors, and they are also interlinked to the risk of testis cancer and poor semen quality. Testicular Dysgenesis Syndrome (TDS) may underlie many cases of all these male reproductive health problems. Genetic defects in androgen production or action can cause both cryptorchidism and hypospadias, but these are not common. A monogenic reason for cryptorchidism or hypospadias has been identified only in a small proportion of all cases. Environmental effects appear to play a major role in TDS. Exposure to several persistent chemicals has been found to be associated with the risk of cryptorchidism, and exposure to anti-androgenic phthalates has been shown to be associated with hormonal changes predisposing to male reproductive problems. Despite progress in identification of endocrine-disrupting substances, we are still far from knowing all the risk factors for these birth defects, and advice for prevention must be based on precautionary principles.

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

“…49 It is important to emphasize the marked geographical differences in the last secular trend in male reproductive function. [50][51][52] The explanation for this regional trend is not known. Giwercman and LundgergGiwercman 46 argue that the population may genetically differ, but that probably environmental or life style related factors are operating.…”

Teasing out the role of aromatase in the healthy and diseased testis

“…More recently, exposure to environmental estrogens has been interlinked to poor semen quality and many male reproductive tract disorders including cryptorchidism, hypospadias and testicular cancer. [7][8][9] From this, many questions have arisen regarding the specific contribution of aromatase to testicular development and disease. Aromatase mRNA has been identified in all somatic cells, germ cells and spermatids within the testis and moreover spermatozoa in the epididymis across species (reviewed in ref.…”

Falling sperm counts twenty years on: where are we now?

“…19 In addition, environmental estrogens acting during pregnancy were proposed to be responsible for a spectrum of additional, related male reproductive tract disorders including hypospadias and cryptorchidism, known collectively as the testicular dysgenesis syndrome (TDS). 20 There is good evidence to suggest that environmental estrogens are contaminating our waterways and having an impact on the sexual differentiation of aquatic organisms. 21 Furthermore, the evidence that such compounds are affecting human reproductive health is less compelling.…”