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Acute response of testicular interstitial tissue in rats to the cytotoxic drug ethane dimethanesulphonate

An ultrastructural and hormonal assay study

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Summary

The cytotoxic effects of ethane dimethanesulphonate upon rat Leydig cells were examined ultrastructurally up to 3 days after treatment and related to changes in serum levels of gonadotrophins and testosterone. Six hours after administration of ethane dimethanesulphonate the usual tubulo-vesicular morphology of Leydig-cell smooth endoplasmic reticulum was converted to small vesicles and the Golgi apparatus showed focal hypertrophy into anastomosing tubules. These changes became more marked by 12 h with many Leydig cells exhibiting karyopyknosis and hyperchromatism. Necrotic Leydig cells were often engulfed by macrophages, the latter containing pyknotic fragments of Leydig cells within their cytoplasm. One day after administration, advanced necrosis of Leydig cells occurred, many of which were phagocytosed by macrophages, and on day 3, destruction of Leydig cells was complete resulting in their elimination from the interstitial tissue, which contained only loose connective tissue and macrophages. Structural alterations to the Leydig cells from 6–24 h was reflected by a significant reduction in serum testosterone levels which further declined to the limits of detection accompanying the abolition of Leydig cells on day 3. These changes were paralleled by a significant elevation of serum LH and FSH levels suggesting diminished feedback regulation of pituitary gonadotrophin secretion. The results indicate that ethane dimethanesulphonate is a rapidly acting Leydig cell toxin which may be a useful experimental tool in further studies of spermatogenic function mediated via Sertoli cell-Leydig cell interaction.

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References

  • Aquilano DR, Dufau ML (1984) Functional and morphological studies on isolated Leydig cells: purification by centrifugal elutriation and metrizamide fractionation. Endocrinology 114:499–510

    Google Scholar 

  • Bergh A (1985) Effect of cryptorchidism on the morphology of testicular macrophages: evidence for a Leydig cell-macrophage interaction. Int J Androl 8:86–96

    Google Scholar 

  • Breucker H (1978) Macrophages, a normal component in seasonally involuting testes of the swan, Cygnus olor. Cell Tissue Res 193:463–471

    Google Scholar 

  • Bu'Lock DE, Jackson CM (1971) Suppression of testicular androgen synthesis in the rat by ethylene dimethane-sulphonate. Gynec Invest 2:305–308

    Google Scholar 

  • Bu'Lock DE, Jackson CM (1975) Suppression of testicular androgen synthesis in the rat by ethane 1,2, dimethanesulphonate. J Steroid Biochem 6:1181–1185

    Google Scholar 

  • Bu'Lock DE, Jones P (1976) Effect of ethane 1,2-dimethanesulphonate on the cyclic AMP response in rat testis to stimulation by HCG. J Reprod Fertil 47:151–153

    Google Scholar 

  • Christensen AK (1975) Leydig cells. In: Hamilton DW, Greep RO (eds) Handbook of physiology, Sect 7, Vol 5. Williams and Wilkins, Baltimore, pp 57–94

    Google Scholar 

  • Christensen AK, Gillim W (1969) The correlation of fine structure and function in steroid-secreting cells, with emphasis on those of the gonads. In: McKern KW (ed) The gonads. Appleton Century Crofts, New York, pp 415–488

    Google Scholar 

  • Cooke BA, Magee-Brown R, Golding M, Dix CJ (1981) The heterogeneity of Leydig cells from mouse and rat testes. Evidence for a, Leydig cell cycle? Int J Androl 4:355–366

    Google Scholar 

  • Cooper ERA, Jackson H (1970) Comparative effects of methylene, ethylene and propylene dimethanesulphonates on the male rat reproductive system. J Reprod Fertil 23:103–108

    Google Scholar 

  • de Kretser DM (1982) Sertoli cell-Leydig cell interaction in the regulation of testicular function. Int J Androl Supp 5:11–17

    Google Scholar 

  • de Kretser DM, Kerr JB (1983) The effect of testicular damage on Sertoli and Leydig cell function. In: de Kretser DM, Burger HG, Hudson B (eds) The pituitary and the testis. Clinical and experimental studies. Springer, Berlin, pp 133–154

    Google Scholar 

  • Fraser HM, Sandow J (1977) Gonadotrophin release by a highly active analog of luteinizing hormone releasing hormone in rats immunized against luteinizing hormone releasing hormone. J Endocrinol 74:291–296

    Google Scholar 

  • Gomes WR (1970) Chemical agents affecting testicular function and male fertility. In: Johnson Ad, Gomes WR, Vandemark NL (eds) The testis, vol 3, Academic Press, New York, pp 483–554

    Google Scholar 

  • Gunn SA, Gould TC (1970) Cadmium and other mineral elements. In: Johnson AD, Gomes WR, Vandermark NL (eds) The testis, vol 3, Academic Press, New York, pp 377–481

    Google Scholar 

  • Hay MF, Allen WR (1975) An ultrastructural and histochemical study of the interstitial cells in the gonads of the fetal horse. J Reprod Fertil Supp 23:557–561

    Google Scholar 

  • Holstein AF (1978) Spermatophagy in the seminiferous tubules and excurrent ducts of the testis in rhesus monkey and in man. Andrologia 10:331–352

    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 (1948) The biology of the interstitial cells of the testis. Rec Prog Horm Res 3:173–195

    Google Scholar 

  • Hooker CW (1970) The intertubular tissue of the testis. In: Johnson AD, Gomes WR, van de Mark NL (eds) The testis, vol 1, Academic Press, New York, pp 483–550

    Google Scholar 

  • Jackson CM, Jackson H (1984) Comparative protective actions of gonadotrophins and testosterone against the antispermatogenic action of ethane dimethanesulphonate. J Reprod Fertil 71:393–401

    Google Scholar 

  • Jackson CM, Morris ID (1977) Gonadotrophin levels in male rats following impairment of Leydig cell function by ethylene dimethanesulphonate. Andrologia 9:29–35

    Google Scholar 

  • Kaler LW, Neaves WB (1978) Attrition of the human Leydig cell population with advancing age. Anat Rec 192:513–518

    Google Scholar 

  • Kerr JB, Mayberry RA, Irby DC (1984) Morphometric studies on lipid inclusions in Sertoli cells during the spermatogenic cycle in the rat. Cell Tissue Res 236:699–709

    Google Scholar 

  • Kerr JB, Donachie K, Rommerts FFG (1985a) Selective destruction and regeneration of rat Leydig cells in vivo. A new method for the study of seminiferous tubular-interstitial tissue interaction. Cell Tissue Res 242:145–156

    Google Scholar 

  • Kerr JB, Robertson DM, de Kretser DM (1985b) Morphological and functional characterisation of interstitial cells from mouse testes fractionated on Percoll density gradients. Endocrinology 116:1030–1043

    Google Scholar 

  • Lording DW, de Kretser DM (1972) Comparative ultrastructural and histochemical studies of the interstitial cells of the rat testis during fetal and postnatal development. J Reprod Fertil 29:261–269

    Google Scholar 

  • Miller SC, Bowman BM, Rowland HG (1983) Structure, cytochemistry, endocytic activity, and immunoglobulin (Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anat 168:1–13

    Google Scholar 

  • Morris ID (1985) Leydig cell resistance to the cytotoxic effect of ethylene dimethanesulphonate in the adult rat testis. J Endocrinol 105:311–316

    Google Scholar 

  • Morris ID, Jackson CM (1978) Gonadotrophin response after castration and selective destruction of the testicular interstitium in the normal and aspermatogenic rat. Acta Endocrinol 88:38–47

    Google Scholar 

  • Morris ID, McCluckie JA (1979) Temporal changes in serum androgen after temporary impairment of Leydig cell function by ethane-1,2-dimethane sulphonate. J Steroid Biochem 10:467–469

    Google Scholar 

  • Parvinen M (1982) Regulation of the seminiferous epithelium. Endocrine Rev 3:404–417

    Google Scholar 

  • Payne AH, Downing JR, Wong KL (1980) Luteinizing hormone receptors and testosterone synthesis in two distinct populations of Leydig cells. Endocrinology 106:1424–1429

    Google Scholar 

  • Rommerts FFG, Grootenhuis AJ, Hoogerbrugge JW, van der Molen HJ (1985) Ethane dimethanesulphonate (EDS) specifically inhibits LH stimulated steroidogenesis in Leydig cells isolated from mature rats but not in cells from immature rats. Molec Cell Endocrinol 42:105–111

    Google Scholar 

  • Roosen-Runge EG, Anderson D (1959) The development of the interstitial cells in the testis of the albino rat. Acta Anat 37:125–137

    Google Scholar 

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

    Google Scholar 

  • Sharpe RM (1982) The hormonal regulation of the Leydig cell. In: Finn CA (ed) Oxford reviews of reproductive biology, vol 4, Oxford, University Press, pp 241–317

    Google Scholar 

  • Sharpe RM (1983) Local control of testicular function. Quart J Exp Physiol 68:265–287

    Google Scholar 

  • Sharpe RM (1984) Intratesticular factors controlling testicular function. Biol Reprod 30:29–49

    Google Scholar 

  • Sharpe RM, Bartlett JMS (1985) Intratesticular distribution of testosterone in rats and the relationship to the concentrations of a peptide that stimulates testosterone secretion. J Reprod Fertil 73:223–236

    Google Scholar 

  • Tapanainen J, Kuopio T, Pelliniemi LJ, Huhtaniemi I (1984) Rat testicular endogenous steroids and number of Leydig cells between the fetal period and sexual maturity. Biol Reprod 31:1027–1035

    Google Scholar 

  • Vermeulen A (1982) Effects of drugs on Leydig cell function. Int J Andrology Supp 5:163–182

    Google Scholar 

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Authors and Affiliations

  1. MRC Reproductive Biology Unit Centre for Reproductive Biology, Edinburgh, Scotland

    Jeffrey Kerr, J. M. S. Bartlett & K. Donachie

  2. Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, Edinburgh, Scotland

    K. Donachie

Authors
  1. Jeffrey Kerr
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  2. J. M. S. Bartlett
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  3. K. Donachie
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Kerr, J., Bartlett, J.M.S. & Donachie, K. Acute response of testicular interstitial tissue in rats to the cytotoxic drug ethane dimethanesulphonate. Cell Tissue Res. 243, 405–414 (1986). https://doi.org/10.1007/BF00251057

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  • DOI: https://doi.org/10.1007/BF00251057

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