Abnormal Germ Cell Development in Cryptorchidism

Abstract

Background: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2–3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4–5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. Patients: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. Materials and Methods: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. Results: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2–3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4–5 years of age indicating a defect in the onset of meiosis. Conclusion: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2–3 months of age and fail to establish adequate meiosis which normally occurs at 4–5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.

Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue

“…At a recent examination at an average age of 19 years (95% CI [18][19][20][21][22], all males were in a healthy condition. They all had Tanner V stage of sexual development and normal erectile function.…”

“…This insufficient testosterone secretion is responsible for impaired transformation of gonocytes into Ad spermatogonia (4,5,11,(15)(16)(17). Additional rationale for LH-RHa treatment was based on the histological analyses of undescended testes in infancy (4,5,11,(15)(16)(17)(18)(19)(20). ment of impaired mini-puberty should be performed before this age.…”

Effects of human chorionic gonadotropin on the normal testicular tissue of rats

“…Treatment timing has been based on the knowledge that delay and defect in the pre-pubertal maturation of germ cells is associated with a reduction in the number of germ cells in cryptorchidism 23 . Pre-pubertal treatment with hormones could, theoretically, achieve a normal maturation and proliferation of germ cells by increasing the total number of these cells and improving the fertility rates 24 .…”

Hydroxysteroid Dehydrogenases – Localization, Function and Regulation in the Testis

“…Other evidences collected over the years have indicated that increased testicular temperature negatively influences the development and differentiation of Leydig cells causing impairments in sex hormones biosynthesis (Huff et al, 2001;Kotula-Balak et al, 2001;Pinart et al, 2000).…”