Role of Hormones, Genes, and Environment in Human Cryptorchidism
Carlo Foresta,
Daniela Zuccarello,
Andrea Garolla and
Alberto Ferlin
University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology, and Centre for Male Gamete Cryopreservation, 35121 Padova, Italy
Correspondence: Address all correspondence and requests for reprints to: Prof. Carlo Foresta, University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova, Italy. E-mail: carlo.foresta{at}unipd.it
Cryptorchidism is the most frequent congenital birth defectin male children (2–4% in full-term male births), andit has the potential to impact the health of the human male.In fact, although it is often considered a mild malformation,it represents the best-characterized risk factor for reducedfertility and testicular cancer. Furthermore, some reports havehighlighted a significant increase in the prevalence of cryptorchidismover the last few decades. Etiology of cryptorchidism remainsfor the most part unknown, and cryptorchidism itself might beconsidered a complex disease. Major regulators of testiculardescent from intraabdominal location into the bottom of thescrotum are the Leydig-cell-derived hormones testosterone andinsulin-like factor 3. Research on possible genetic causes ofcryptorchidism has increased recently. Abundant animal evidencesupports a genetic cause, whereas the genetic contribution tohuman cryptorchidism is being elucidated only recently. Mutationsin the gene for insulin-like factor 3 and its receptor and inthe androgen receptor gene have been recognized as causes ofcryptorchidism in some cases, but some chromosomal alterations,above all the Klinefelter syndrome, are also frequently involved.Environmental factors acting as endocrine disruptors of testiculardescent might also contribute to the etiology of cryptorchidismand its increased incidence in recent years. Furthermore, polymorphismsin different genes have recently been investigated as contributingrisk factors for cryptorchidism, alone or by influencing susceptibilityto endocrine disruptors. Obviously, the interaction of environmentaland genetic factors is fundamental, and many aspects have beenclarified only recently.
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