The Effects of Ethylene Dimethane Suiphonate (EDS) on Rat Leydig Cells: Evidence to Support a Connective Tissue Origin of Leydig Cells1

Abstract

Ethylene dimethane sulphonate (DS) administered to adult male rats in a single dose of 75 mg/kg body weight results in a rapid destruction of Leydig cells which, in turn, is associated with a marked decline in levels of serum testosterone. For 24-72 h after treatment with EDS (post-EDS) the Leydig cells undergo degenerative changes consisting of chromatin condensation and cytoplasmic vacuolation, and testicular macrophages progressively remove Leydig cells from the intertubular tissue by phagocytosis. This results in the total absence of Leydig cells on Days 7-14 and the absence of any detectable specific 125I-hCG binding to testis homogenates. Associated with the low levels of serum testosterone, levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum rise, LH to levels found in castrate rats. Morphometric and 125I-hCG binding studies indicate that a new generation of Leydig cells develop from Day 21 and reach control levels by Day 49. Morphologic observations suggest that the Leydig cells arise by differentiation from a pool of connective tissue cells that includes fibroblasts, lymphatic endothelial cells and pericytes. The new Leydig cells, which appear around Day 21 post-EDS, have the features of fetal Leydig cells. The latter appear to transform into Leydig cells typical of normal adult rats between 35-49 days post-EDS. The differentiation of new Leydig cells is associated with a reestablishment of normal levels of testosterone 21 days post-EDS. Serum LH and FSH return to normal at 28 days and 49 days respectively.

Proliferative and Nonproliferative Lesions of the Rat and Mouse Male Reproductive System

“…40, No. 6S, 2012 LESIONS OF THE MALE REPRODUCTIVE SYSTEM 49S atrophy of the male mammary gland (Creasy 2008 (Bartlett, Kerr, and Sharpe 1986;Jackson et al 1986;Molenaar et al 1985). response.…”

Turnover Time of Leydig Cells and Other Interstitial Cells in Testes of Adult Rats

“…Peritubular cells and perivascular cells may be the stem cells or precursor cells of the Leydig cells [2,8,9,15,161. This assumption is supported by the fact that, after the destruction of the existing population of Leydig cells by EDS or daily hCG treatment (when the proliferative activity of intersti-tial cells is greatly enhanced), most labeled interstitial cells are located peritubularly and perivascularly [16].…”

Mitotic activity in monkey and rat Leydig cells

“…The concept of Leydig cell precursors has recently received morphological and functional support (Kerr et a/., 1985a,b ;Morris et al, 1986 ;Jackson et al, 1986 ;Risbridger et al, 1987). It is also believed that Leydig cells are able to divide (Christensen, 1975).…”

“…A number of experimental models have been developed in rats, inducing either Leydig cell hyperplasia (Chemes et al, 1976 ;Aoki and Fawcett, 1978 ;Kerr et al, 1979 ;Christensen and Peacock, 1980) or destruction followed by extensive regeneration (Kerr et al, 1985b ;Morris et al, 1986 ;Jackson et al, 1986 ;Risbridger et al, 1987 (Orth, 1982) …”