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Background: The crucial involvement of estradiol in the etiology of experimental cryptorchidism has been well established since 1938. Estradiol injected into pregnant rodents induced either uni- or bilateral cryptorchidism in 75-100% of the male offspring, while concomitantly lowering significantly testicular testosterone and causing atrophy of Leydig cells due to an impaired gonadotropin secretion. An impaired secretion of gonadotropin was found also in cryptorchid boys. This had an impact on the development of Leydig cells resulting in insufficient testosterone secretion. It has been argued convincingly that the increasing incidence of reproductive abnormalities in the human male may be related to increased estrogen exposure in utero Consumption of estrogen by mothers during the first four months of pregnancy has been implicated in cryptorchidism. In the present study, we document the expression of estradiol in the syncytial trophoblast of boys born with cryptorchidism compared to the placentas of boys and girls born with normal genitalia. Methods: Biopsies of the newborn placenta were fixed in glutaraldehyde and embedded in Epon for immunohistological procedures. The genitalia of the newborn were examined immediately after birth. Those boys with either unilateral or bilateral cryptorchidism were reexamined after one year and followed until treatment. Seven boys in this study had cryptorchidism: six unilateral, one bilateral. Semi-thin histological sections of placental biopsies of these seven boys together with seven randomly selected normal male and seven female placentas were analyzed immunohistochemically with a polyclonal anti-estradiol-17/[Beta] antibody, identified with a second antibody conjugated with peroxidase. Results: The placental villi in all seven cryptorchid boys had a normal microscopic anatomical structure. The weak expression of the estradiol in the placentas of both the normal males and females was localized predominately as the basal part of the syncytiotrophoblast in the terminal placental villi. In contrast, all of the placentas of the cryptorchid boys had a strong expression of estradiol at the basal portion of the syncytiotrophoblast. Conclusion: Our findings of an increased expression of estradiol as a result of an abnormal function of syncytiotrophoblast seemingly have an impact on testicular descent. This hypothesis may explain the nature of hypogonadotropic-hypogonadism found frequently in cryptorchid boys., F. Hadziselimovic, M.D., FAAP; R. Geneto, L.R. Emmons, Ph.D. University Clinics, Children's Hospital, Basel; Kinder Tages Klinik, Liestal, [...]