Disorders of testicular development (gonadal dysgenesis) from fetal life to the adulthood

Abstract

Disorders of testicular development (gonadal dysgenesis) in fetal life are associated with disorders of their hormonal and gametogenic activity in the adulthood. The lack or reduction of testosterone secretion by the fetal Leydig cells lead to disorders in the differentiation of male internal and external genital organs as well as disturbances in the determination of the psychic sex. Abnormal secretion of anti-Müllerian hormone (AMH) by Sertoli cells is associated with the survival of Müllerian ducts and the presence of female internal genitalia in individuals with a male genetic sex. A further clinical consequence of organogenesis disturbances is the development of hypergonadotrophic hypogonadism during the period of expected puberty and lack of fertility. However, in addition to the classic gonadal dysgenesis, which reveals the reverse of sexual characteristics, there are probably its incomplete, latent forms. There are no disorders of sexual differentiation, but "milder" disorders such as cryptorchidism, decreased fertility and increased risk of testicular germ cell tumours (GCT). All of these disorders probably have a common etiology, thus it was proposed to create one clinical syndrome called the testicular dysgenesis syndrome (TDS).

In the last 60 years, there has been a progressive increase in the incidence of disorders belonging to the TDS syndrome. It is believed that they may be caused by pollution of the natural environment as a result of the development of modern civilization. Adverse effects on the male sexual system are primarily caused by the so-called xenoestrogens. They have a variable chemical structure and occur among synthetic substances of industrial, agricultural and medical use. They can bind to the estrogen receptor and mimic the action of estrogens, and can also act as antiandrogens. Some xenoestrogens accumulate in the food network, and thus become potentially harmful not only to living organisms, but also to future generations. Notable involvement in the male fertility disorder is also attributed to environmental factors such as elevated temperature, electromagnetic radiation, chronic stress, obesity, sedentary lifestyle, as well as smoking and alcohol abuse. The consequence of most of these factors is oxidative stress, which is caused by the imbalance between the production of so-called reactive oxygen species (ROS) and the protective antioxidant system responsible for their neutralization and elimination. ROS leads to a reduction in sperm count, impaired function, decreased motility and abnormal morphology and DNA damage, and ultimately impaired fertilization or embryo development. Most environmental factors associated with lifestyle are modifiable. Improvement in the quality of semen and fertility parameters can also be achieved in some cases by using antioxidant substances.