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Objective To characterize lysosomes and histochemical function of granular Sertoli cells in developmental alterations. Design Prospective and retrospective study. Setting University hospital and research centers. Patient(s) Nineteen infantile and pubertal patients undergoing testicular biopsy; four rat testes for lysosomal study. Intervention(s) CD-68, α-1-antitrypsin, vimentin, inhibin α subunit, and anti-mullerian hormone antibodies were evaluated. Morphometric measures in seminiferous tubules with and without granular Sertoli cells were obtained. Ultrastructural data of lysosomes in human and rat Sertoli cells were compared. Main Outcome Measure(s) Quantification of mean diameter of seminiferous tubules, tubular fertility index, and germ and Sertoli cell indexes were obtained in human testis. Result(s) Granular changes in Sertoli cells are due to the accumulation of large amounts of lysosomes. Vimentin immunoexpression in infantile and pubertal granular Sertoli cells was lower than in adjacent nongranular Sertoli cells. Inhibin was negative in granular cells. Anti-mullerian hormone–positive and -negative granular Sertoli cells were present within the same tubules. Conclusion(s) The presence of early granular changes in Sertoli cells in childhood and pubertal cryptorchidic patients, associated with other developmental alterations, suggests an intense and irreversible dysfunction of phagocytosis in the granular Sertoli cells. These alterations might be considered primary and irreversible anomalies of Sertoli cells, which might be contributing factors in the infertility seen in these patients.

A hormonal and quantitative light microscopy study of one man with macro-orchidism associated with mental retardation and fragile X chromosome (case no. 1) and three men with idiopathic macro-orchidism (cases no. 2 to 4) is reported. Hormonal study revealed slightly increased follicle-stimulating hormone serum levels in cases no. 1 to 3. The testes from cases no. 1 (orchidoepididymoectomy specimen) and 2 (testicular biopsy) presented interstitial edema and three different tubular patterns that were arranged in a mosaic-like manner. Type I tubules had an increased diameter (less than 220 microns), dilated lumen, and thin seminiferous epithelium usually consisting of Sertoli cells, spermatogonia, primary spermatocytes, and sometimes a few spermatids. Type II tubules had a normal diameter (180 to 220 microns) and germ cell development varied between complete spermatogenesis and Sertoli-cell-only tubules. Type III tubules had decreased diameter (less than 180 microns), atrophic seminiferous epithelium, and thickened tunica propria. The appearance of the nuclei of the Sertoli cells in the three types of tubules could be either mature or immature. Some of the mature Sertoli cells presented a granular cytoplasm. A few of these granular cells grouped together, forming nests that protruded into the tubular lumen. The testicular biopsies from cases no. 3 and 4 only presented type II tubules that contained both mature and immature Sertoli cells. Quantitative study revealed that the large testicular size was principally due to an increased tubular length in all four cases. Although the seminiferous tubule lesions and interstitial edema suggest an obstructive process, the testicular excretory ducts (studied in case no. 1) appeared normal or only slightly dilated. It is possible that the seminiferous tubule lesions (dilated lumen and germ cell depletion) might be secondary to the Sertoli cell lesions (granular cytoplasm and nuclear immature-like pattern.