Cryptorchidism

Abstract

Cryptorchidism is a very common anomaly of the male genitalia, affecting 2%-4% of male infants and is more common in premature infants. There are two separate stages of testicular descent. The first stage occurs at 8-15 weeks' gestation in the human fetus and is characterized by enlargement of the genito-inguinal ligament, or gubernaculum, and regression of the cranial suspensory ligament. The testis remains close to the future inguinal region as the fetal abdomen grows. Leydig cells in the testis produce insulin-like hormone 3, which stimulates the caudal gubernaculum to grow and become thicker. Mullerian inhibiting substance may have a role in the first phase of descent by stimulating the swelling reaction in the gubernaculum. The second phase of testicular descent requires migration of the gubernaculum and testis from the inguinal region to the scrotum, between 25 and 35 weeks' gestation. The genitofemoral nerve releases calcitonin gene-related peptide, a neurotransmitter that provides a chemotactic gradient to guide migration. The exact cause of cyrptorchidism remains elusive. Information is mainly derived from animal studies (especially in rodents), which may not extrapolate to the human setting. These findings, however, do have some similarities among mammalian species. The current recommended timing for orchidopexy is between 6 and 12 months of life in an effort to preserve the spermatogonia--the stem cells for subsequent spermatogenesis. Despite surgical treatment by orchidopexy, the long-term outcome still remains problematic and controversial. Impaired fertility (33% in unilateral cases and 66% in bilateral undescended testes) and a cancer risk 5-10 times greater than normal is observed over time. Further research into the cause and management of undescended testes is necessary.

Reinke´s Crystals in Perivascular and Peritubular Leydig Cells

“…It has been well established that scrotal sac maintains a temperature even 3-5 ºC lower than that within the abdominal cavity or the human body in general. [25][26][27][28] It can be postulated that a prolonged exposure of the testis to higher temperature stimulated enzymes involved in the accumulation of microfilaments and formation of the crystal. Control group of testes were harboured within the scrotal sac and, therefore, exposed to the normal (lower) temperature which could slow down the activity of enzymes engaged in the crystal formation.…”

“…In humans, the final stages of the descent occur at the end of the pregnancy (month [8][9] and are controlled by insulin-like 3 (INSL3), members of the HOX gene family, testosterone and Müllerian inhibitory substance (MIS). [25][26][27][28] It is thought that these hormones induce a shortening of the gubernaculum testis, a ligament that is attached to the lower pole of each testis. The shortening of the gubernaculum enables the descent of the testis into the scrotal sac, and the development of spermatogenesis at the start of puberty.…”

“…The shortening of the gubernaculum enables the descent of the testis into the scrotal sac, and the development of spermatogenesis at the start of puberty. [25][26][27][28] If the testis has not descended in a regular way, an individual is diagnosed with cryptorchidism. Cryptorchidism is the most frequent disturbance during the development of the male reproductive system in newborns, aborted foetuses, among boys in puberty and in adults.…”

The importance of the gubernaculum in testicular migration during the human fetal period

“…One of the factors involved in cryptorchidism is the failure of the gubernaculum to migrate all the way to the scrotum (38). Structural studies conducted in patients with cryptorchidism reveal significant changes in the gubernaculum's structure, with a higher quantity of fibrous tissue and lower concentration of collagen than in the fetal gubernaculum (39).…”

Spermatogenesis in Cryptorchidism

“…receptor expression, or cell signaling can affect testis position ( 3,4 ) . Candidate gene association analysis of mutant alleles and cryptorchidism in human populations has indicated a possible link between the presence of gene mutations and testicular maldescent; however, the frequency of such associations is rather low and in most cases, the etiology for cryptorchidism remains unknown ( 2,5 ) .…”