Cryptorchidism or undescended testis is one of the most common anomalies encountered in paediatric urology and is estimated to affect 1 to 4 per cent of full term and upto 30 per cent of preterm male neonates. The associated problems of sub-fertility or infertility and malignant transformation have been recognized for long.
Over the last five decades, the concepts related to cryptorchidism have changed dramatically as knowledge about its effects has accrued from research conducted worldwide. The recommended age of orchidopexy has fallen progressively from adolescence to less than one year.
Germ cell development:
Primitive germ cells are present in the testes at the time of birth and are not in ‘suspended animation’ as thought previously. The testis-specific gene activation leads to a timed sequence of events which include regulated cell proliferation and differentiation of spermatogonia, meiosis and haploid differentiation or spermiogenesis.
Appearance of primordial germ cells (PGC) or gonocytes: The embryologic origin of the sperm can be traced back to the PGCs which are formed in the epiblast during the second week and move to the wall of the yolk sac.
These migrate towards the developing gonads by the end of the fifth week. Mitosis continues during and after migration resulting in proliferation. PGCs or the gonocytes act as foetal reservoir of stem cells.
Disappearance of gonocytes (foetal stem cell pool) and appearance of adult dark (Ad) spermatogonia (adult stem cell pool): This is the first major step in the maturation of the hypothalamic-pituitary-testicular axis and is accompanied by establishment of adult stem cell pool which replaces the foetal stem cell pool and a dramatic reduction in the total number of germ cells per tubule.
The Ad spermatogonia exhibit a characteristic dark (electron-dense) cytoplasm and a bright nuclear spot. The transformation starts at 2-3 months of age and is normally complete by six months.
The transformation is believed to be a consequence of a transient surge in the serum hormonal levels (follicular stimulating hormone or FSH, luteinizing hormone or LH and testosterone); this phase has been labelled as ‘mini-puberty’.
Almost simultaneous with the hormonal surge, there is an increase in the testicular weight and volume.
The Ad spermatogonia once formed persist for the rest of life. This process is sensitive to minor genetic aberrations and to adverse environmental conditions; consequently not all neonatal gonocytes are transformed into the Ad spermatogonia and the remaining gonocytes undergo apoptosis
Transient appearance of primary spermatocytes and the prophase of first meiotic division: This is the second crucial step in the maturation of the hypothalamic-pituitary-testicular axis and occurs at 4-5 yr of age.
It is characterized by the transient onset of meiosis and histological appearance of primary spermatocytes with a transient rise in both the germ cell count and Ad spermatogonia count.
Spermatogenesis arrests at this stage and resumes after the onset of puberty.
Why undescended testes cause infertility:
Short answer: Because failure of transformation of gonocytes into Ad spermatogonia
Long Answer: Hadziselimovic and colleagues have suggested that the disappearance of gonocytes (foetal stem cell pool) and appearance of Ad spermatogonia (adult stem cell pool) may be a prerequisite for the normal future spermiogenesis and fertility.
This transformation is delayed and ineffective in cryptorchidism and leads to delay in the establishment of the adult stem cell pool and prolonged persistence of the foetal stem cell pool.
Besides this, the reduction in the number of germ cells per tubule does not take place during this phase and the germ cell count continues to be high as late as the beginning of the second year of life giving a ‘false’ impression of histologically normal cryptorchid testis. Thereafter, the total number of germ cells falls below normal.