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Response of the human testis to long-term estrogen treatment: Morphology of Sertoli cells, Leydig cells and spermatogonial stem cells

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Summary

The present investigation is concerned with the morphological changes observed in human testicular tissue following prolonged estrogen administration. Testicular material obtained from 11 transsexual patients who had been submitted to long-term estrogen treatment prior to sex-reversal surgery was studied by means of light- and electron microscopy.

The testes of all patients examined present a more or less uniform appearance: There are narrow seminiferous cords surrounded by an extensively thickened lamina propria. They contain Sertoli cells and spermatogonia exclusively. There is no evidence of typical Leydig cells.

The persisting spermatogonia show the characteristic features of pale type-A spermatogonia, whereas dark type-A spermatogonia are almost completely eliminated from the epithelium. In view of the fact that spermatogonia that survived radiotherapy and treatment with various noxious agents have recently been regarded as the stem cells of the human testis, it is suggested that also the majority of those spermatogonial types that are less sensitive to disturbances of the endocrine balance may consist of stem cells. The present results, therefore, corroborate the concept that the stem cells of the human testis may be derived from pale type-A spermatogonia or the variants of this cell type.

Sertoli cells display two types of ovoid nuclei. In contrast to untreated material the nuclei lie adjacent to the basal lamina, and organelles and telolysosomes are confined to the apical cytoplasm. The apico-basal differentiation of mature cells, therefore, is not observed. Moreover, typical organelles and inclusions of mature cells are absent, as are the junctional specializations. Thus, Sertoli cells have transformed into immature cells, resembling precursors prior to puberty.

Fibroblast-like cells in the interstitial tissue, which display strongly lobulated nuclei, a well-developed smooth endoplasmic reticulum, lipid droplets, and numerous inclusions are assumed to represent dedifferentiated Leydig cells.

Since after estrogen treatment serum testosterone and gonadotropin levels are known to be reduced, it appears that the morphological changes correlate well with the endocrine status.

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References

  • Aumüller G, Schiller A, Schenck B, Berswordt-Wallrabe RV (1978) Fine structure of Sertoli cells in rat testis after hypophysectomy, testosterone treatment and rcinvolution. Cytobiologie 17:453–463

    PubMed  Google Scholar 

  • Balze de la FA, Mancini RE, Bun GE, Irazu J (1954) Morphologic and histologic changes produced by estrogens on adult human testes. Fertil Steril 5:421–436

    PubMed  Google Scholar 

  • Balze de la FA, Mancini RE, Arrilaga F, Andrada JA, Vilar O, Gurtman AI, Davidson OW (1960) Puberal maturation of the normal human testis. A histologic study. J Clin Endocrinol Metab 20:266–284

    PubMed  Google Scholar 

  • Balze de la FA, Gurtmann AI, Janches M, Arrilaga F, Alvarez AS, Segal L (1962) Effects of estrogens on the adult human testis with special reference to the germinal epithelium. A histologic study. J Clin Endocrinol Metab 22:1251–1261

    PubMed  Google Scholar 

  • Chemes HE, Dym M, Fawcett DW, Javadpour N, Sherins RJ (1977) Patho-physiological observations of Sertoli cells in patients with germinal aplasia or severe germ cell depletion. Ultrastructural findings and hormone levels. Biol Reprod 17:108–123

    PubMed  Google Scholar 

  • Chowdhury AK, Steinberger A, Steinberger E (1975) A quantitative study of spermatogonial population in organ culture of human testis. Andrologia 7:297–307

    Google Scholar 

  • Christensen AK (1975) Leydig cells. In: Hamilton DW, Creep RO (eds) Handbook of Physiology, Section 7: Endocrinology Vol V: Male Reproductive System. Am Phys Soc, Washington DC, pp 57–94

    Google Scholar 

  • Clermont Y (1966) Renewal of spermatogonia in man. Am J Anat 188:509–524

    Google Scholar 

  • Dünn CW (1941) Stilbestrol induced testicular degeneration in hypersexual males. J Clin Endocrinol 1:643–648

    Google Scholar 

  • Dym M, Fawcett DW (1970) The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol Reprod 3:308–326

    PubMed  Google Scholar 

  • Fawcett DW, Burgos MH (1960) Studies on the fine structure of the mammalian testis. II. The human interstitial tissue. Am J Anat 107:245–269

    Google Scholar 

  • Fukuda T, Hedinger Chr, Groscurth P (1975) Ultrastructure of developing germ cells in the fetal human testis. Cell Tissue Res 161:55–70

    PubMed  Google Scholar 

  • Hadziselimović F, Seguchi H (1974) Ultramikroskopische Untersuchungen am Tubulus seminiferus bei Kindern von der Geburt bis zur Pubertät. II. Entwicklung und Morphologie der Sertolizellen. Verh Anat Ges 68:149–161

    PubMed  Google Scholar 

  • Hagenäs L, Plöen L, Ekwall H (1978) Blood-testis barrier: evidence for intact inter-Sertoli cell junctions after hypophysectomy in the adult rat. J Endocrinol 76:87–91

    PubMed  Google Scholar 

  • Halley IBM (1963) The growth of Sertoli cell tumors: a possible index of differential gonadotrophin activity in the male. J Urol 90:220–229

    PubMed  Google Scholar 

  • Holstein AF, Roosen-Runge EC (1981) Atlas of human spermatogenesis. Grosse, Berlin

    Google Scholar 

  • Holstein AF, Wartenberg H, Vossmeyer J (1971) Zur Cytologie der pränatalen Gonadenentwicklung beim Menschen. III. Die Entwicklung der Leydigzellen im Hoden von Embryonen und Feten. Z Anat Entwickl Gesch 135:43–66

    Google Scholar 

  • Hooker CW (1970) The intertubular tissue of the testis. In: Johnson AD, Gomes WR, VanDemark NL (eds) The Testis Vol I. Academic Press, New York, pp 483–550

    Google Scholar 

  • Howard RP, Sniffen RC, Simmons FA, Albright F (1950) Testicular deficiency: a clinical and pathological study. J Clin Endocrinol 10:121–186

    Google Scholar 

  • Huber R, Weber E, Hedinger Chr (1968) Zur mikroskopischen Anatomie der sog. hhypoplastischen Zonen des normal descendierten Hodens. Virchows Arch A (Pathol Anat) 344:47–53

    Google Scholar 

  • Huckins C (1978) Behavior of stem cell spermatogonia in the adult rat irradiated testis. Biol Reprod 19:747–760

    PubMed  Google Scholar 

  • Huckins C, Oakberg EF (1978) Morphological and quantitative analysis of spermatogonia in mouse testes using whole mounted seminiferous tubules. II. The irradiated testis. Anat Rec 192:529–542

    PubMed  Google Scholar 

  • Jackson AE, O'Leary PC, Ayers MM, de Kretser DM (1986) The effects of ethylene dimethane sulphonate (EDS) on rat Leydig cells: Evidence to support a connective tissue origin of Leydig cells. Biol Reprod 35:425–437

    PubMed  Google Scholar 

  • Kerr JB, Donachie K, Rommerts FFG (1985) Selective destruction and regeneration of rat Leydig cells in vivo. Cell Tissue Res 242:145–156

    PubMed  Google Scholar 

  • Kretser de DM (1967) The fine structure of the testicular interstitial cells in men of normal androgenic status. Z Zellforsch 80:594–609

    PubMed  Google Scholar 

  • Kretser de DM (1968) The fine structure of the immature human testis in hypogonadotropic hypogonadism. Virchows Arch A (Pathol Anat) 1:283–296

    Google Scholar 

  • Kretser de DM, Burger HG (1971) Ultrastructural studies of the human Sertoli cell in normal men and males with hypogonadotropic hypogonadism before and after gonadotropic treatment. In: Saxena BB, Beling CG, Gandy HM (eds) Gonadotropins. Wiley Insurance, New York, pp 640–656

    Google Scholar 

  • Leeson CR (1966) An electron microscopic study of cryptorchid and scrotal human testes, with special reference to pubertal maturation. Invest Urol 3:498–511

    PubMed  Google Scholar 

  • Leinonen P, Ruokonen A, Kontturi M, Vihko R (1981) Effects of estrogen treatment on human testicular unconjugated steroid and steroid sulfate production in vivo. J Clin Endocrinol Metab 53:569–573

    PubMed  Google Scholar 

  • Lu CC, Steinberger A (1978) Effects of estrogen on human seminiferous tubules: light and electron microscopic analysis. Am J Anat 153:1–14

    PubMed  Google Scholar 

  • Mancini RE, Nolazco J, Baize de la FA (1952) Histochemical study of normal adult human testis. Anat Rec 114:127–148

    PubMed  Google Scholar 

  • Mancini RE, Narbaitz R, Lavieri JC (1960) Origin and development of the germinative epithelium and Sertoli cells in the human testis: cytological, cytochemical and quantitative study. Anat Rec 136:477–489

    PubMed  Google Scholar 

  • Mancini RE, Vilar O, Lavieri JC, Andrada JA, Heinrich JJ (1963) Development of Leydig cells in the human testis. A cytological, cytochemical and quantitative study. Am J Anat 112:203–214

    Google Scholar 

  • Oakberg EF (1971) A new concept of spermatogonial stem-cell renewal in the mouse and its relationship to genetic effects. Mutat Res 11:1–7

    PubMed  Google Scholar 

  • Oakberg EF (1975) Effects of radiation on the testis. In: Hamilton DW, Greep RO (eds) Handbook of Physiology, Section 7: Endocrinology Vol V: Male Reproductive System. Am Phys Soc, Washington DC, pp 233–243

    Google Scholar 

  • Oshima H, Sarada T, Ochiai K, Tamaoki B (1974) Effects of a synthetic estrogen upon steroid bioconversion in vitro in testes of patients with prostatic cancer. Invest Urol 12:43–49

    PubMed  Google Scholar 

  • Payer AF, Meyer WJ, Walker PA (1979) The ultrastructural response of human Leydig cells to exogenous estrogens. Andrologia 11:423–436

    PubMed  Google Scholar 

  • Pelliniemi LJ, Niemi M (1969) Fine structure of the human foetal testis. I. The interstitial tissue. Z Zellforsch 99:507–522

    PubMed  Google Scholar 

  • Plattner D (1962) Hypoplastische und keimepithelfreie Zonen in beidseits deszendierten Hoden als Zeichen einer partiellen Dysgenesie. Virchows Arch A (Pathol Anat) 335:598–616

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J Cell Biol 17:208–212

    PubMed  Google Scholar 

  • Rodriguez-Rigau LJ, Tcholakian RK, Smith KD, Steinberger E (1977) In vitro steroid metabolic studies in human testes. I. Effects of estrogen on progesterone metabolism. Steroids 29:771–787

    PubMed  Google Scholar 

  • Schulze C (1979) Morphological characteristics of the spermatogonial stem cells in man. Cell Tissue Res 198:191–199

    PubMed  Google Scholar 

  • Schulze C (1981) Survival of human spermatogonial stem cells in various clinical conditions. In: Holstein AF, Schirren C (eds) Advances in Andrology Vol 7: Föhringer Symposium: Stem cells in spermatogenesis. Grosse, Berlin, pp 58–68

    Google Scholar 

  • Schulze C (1984) Sertoli cells and Leydig cells in man. Adv Anat Embryol Cell Biol 88:1–104

    PubMed  Google Scholar 

  • Schulze C, Holstein AF, Schirren C, Körner F (1976) On the morphology of the human Sertoli cells under normal conditions and in patients with impaired fertility. Andrologia 8:167–178

    PubMed  Google Scholar 

  • Schulze W (1978) Lichtund elektronenmikroskopische Studien an den A-Spermatogonien von Männern mit intakter Spermatogenese und bei Patienten nach Behandlung mit Antiandrogenen. Andrologia 10:307–320

    PubMed  Google Scholar 

  • Slaunwhite WR, Sandberg AA, Jackson JE, Staubitz WJ (1962) Effects of estrogen and HCG on androgen synthesis by human testes. J Clin Endocrinol Metab 22:992–995

    PubMed  Google Scholar 

  • Sniffen RC (1950) The testis. I. The normal testis. Arch Pathol 50:259–284

    Google Scholar 

  • Sohval AR (1956) Testicular dysgenesis in relation to neoplasm of the testicle. J Urol 75:285–291

    PubMed  Google Scholar 

  • Vilar O (1970) Histology of the human testis from neonatal period to adolescence. In: Rosemberg E, Paulsen CA (eds) The Human Testis. Plenum Press, New York, pp 95–108

    Google Scholar 

  • Vitale R, Fawcett DW, Dym M (1973) Normal development of the blood-testis barrier and the effects of clomiphene and estrogen treatment. Anat Rec 176:333–344

    Google Scholar 

  • Wartenberg H, Holstein AF, Vossmeyer J (1971) Zur Cytologie der pränatalen Gonadenentwicklung beim Menschen. II. Elektronenmikroskopische Untersuchungen über die Cytogenese von Gonozyten und fetalen Spermatogonien im Hoden. Z Anat Entw Gesch 134:165–185

    Google Scholar 

  • Welch WJ, Suhan JP (1985) Morphological study of the mammalian stress response: Characterization of changes in cytoplasmic organelles, cytoskeleton, and nucleoli, and appearance of intranuclear actin filaments in rat fibroblasts after heat-shock treatment. J Cell Biol 101:1198–1211

    PubMed  Google Scholar 

  • Withers HR, Hunter N, Barkley HT, Reid BO (1974) Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis. Radiat Res 57:88–103

    PubMed  Google Scholar 

  • Yanaihara T, Troen P (1972) Studies of the human testis. III. Effects of estrogen on testosterone formation in human testis in vitro. J Clin Endocrinol Metab 34:968–973

    PubMed  Google Scholar 

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  1. Abteilung für Funktionelle Anatomie am Anatomischen Institut der Universität Hamburg, Hamburg, Bundesrepublik Deutschland

    Cornelia Schulze

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Schulze, C. Response of the human testis to long-term estrogen treatment: Morphology of Sertoli cells, Leydig cells and spermatogonial stem cells. Cell Tissue Res. 251, 31–43 (1988). https://doi.org/10.1007/BF00215444

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