Environmental oestrogens disrupt testicular descent and damage male reproductive health: Mechanistic insight

Abstract

Environmental oestrogens (EEs) as environmental pollutants have been paid much attention due to their impact on congenital malformation of male genitourinary system. Exposure to EEs for prolonged time could hinder testicular descent and cause testicular dysgenesis syndrome. Therefore, it is urgent to understand the mechanisms by which EEs exposure disrupt testicular descent. In this review, we summarize recent advances in our understanding of the process of testicular descent, which is regulated by intricate cellular and molecular networks. Increasing numbers of the components of these networks such as CSL and INSL3 are being identified, highlighting that testicular descent is a highly orchestrated process that is essential to human reproduction and survival. The exposure to EEs would lead to the imbalanced regulation of the networks and cause testicular dysgenesis syndrome such as cryptorchidism, hypospadias, hypogonadism, poor semen quality and testicular cancer. Fortunately, the identification of the components of these networks provides us the opportunity to prevent and treat EEs induced male reproductive dysfunction. The pathways that play an important role in the regulation of testicular descent are promising targets for the treatment of testicular dysgenesis syndrome.

Keywords: INSL3; androgen; environmental oestrogen; infertility; testicular dysgenesis syndrome; undescended testes.

FIGURE 1

The development of testicular descent. The primitive gonad is located around the kidney, held by the cranial suspensory ligament (CSL) and the gubernaculum testis. During transabdominal phase, androgen‐mediated dissolution of the CSL and insulin‐like factor 3 (INSL3) mediated swelling of the gubernaculum would bring the testis down to the inguinal canal. Next, during inguinoscrotal phase, the testis would passe the inguinal canal into the scrotum dependent on the action of testosterone. Adapted from Ref.

FIGURE 2

Proposed mechanisms by which EEs disrupt testicular descent and damage male reproductive health. The exposure to EEs during pregnancy causes damage to the gubernaculum, Leydig cells and Sertoli cells in the foetal gonad, and disrupt the metabolism of testosterone. Consequently, the foetus will develop testicular dysgenesis syndrome such as cryptorchidism, hypospadias, hypogonadism, poor semen quality and testicular cancer.