Ultrastructural Abnormalities of Epididymal Tissues in XXSXR Pseudomale (Sex-Reversed) Mice

Abstract

Sex reversed (Sxr), a duplication of the Y chromosomal testis-determining factor in mice, causes testis development in XXSxr animals. No effects of Sxr on nongonadal organs are expected. However, we have previously shown that the epididymis of XXSxr pseudomale (sex-reversed) mice lacks the Initial Segment. In the present study we examined the ultrastructure of the head of the epididymis of adult and 21-day old XXSxr pseudomale mice. Epithelial cells of both adult and juvenile XXSxr animals contain numerous vesicles, some within mitochondria. The basal lamina is thickened and infolded. The periepithelial layer is abnormally thick, with distorted smooth muscle cells and fibrocytes that also contain lysosomelike vesicles, often in mitochondria, and excessively wide intercellular spaces. Normal collagen fibrils are infrequent; they are in part replaced by wisps of nondiscrete material, possibly immature collagen. Sxr is known to affect spermatogenesis and Sertoli cells. The abnormal conjugation of sex-determining genes in XXSxr appears also to subvert mesenchymal-epithelial development in both epididymis and testis. We believe the most likely explanation of our data is that the X X S x r genotype is not testis specific but also influences the epididymis directly.

Development of the normal XY male and sex‐reversed XXSxr pseudomale mouse epididymis

“…Various other possible explanations do exist (LeBarr and and are under study. Data from electron microscopic studies of the XXSxr pseudomale reveal abnormalities of both epithelium and connective tissue in the epididymis (Wilkinson et al, 1988), and similar connective tissue abnormalities in the testis (Sweeny et al, 1986). These findings, like the other data now available, suggest that systemic effects, or factors reaching the epididymal duct lumen via testicular fluid, are less likely explanations of the epididymal abnormalities than are intrinsic genotypic effects.…”

Aberrant anogenital distance in XXSxv (‘sex‐reversed’) pseudomale mice

“…In addition, at least some secondary sexual development in eutherian mammals may be partially dependent on chromosomal sex. For example, although the pseudomale mouse is fully androgenized, its epididymis is abnormal (Le Le Barr, Blecher & Moger, 1986;Wilkinson et al, 1988;Le Barr et a/., 1991), and androgen treatment fails to normalize the development, though other organs d o react to the extrinsic androgen (Le Barr et u/., 1986). A further example is the Klinefelter syndrome in humans (for which the XXSxr mouse is in some respects a model).…”

“…The mice used were from an Sxr-congenic line of the inbred strain DCH (Kirkeby & Blecher, 1981;Wilkinson et a/., 1988;Le Barr, Blecher & Moger, 1991). The animals were housed according to guidelines…”

“…Because these X X S w 'sex-reversed males' have female chromosomal constitution they are, by definition, pseudohermaphrodites (Nora & Fraser, 1989). Furthermore, they diverge in several traits from the normal male phenotype (Le Wilkinson, Sweeny & Blecher, 1988). We refer to these 'sex-reversed' X X S x r mice as pseudomales because, although they are by and large male in phenotype, and have thus clearly followed a mainly male developmental pathway, they are chromosomally and genetically not true males.…”

Extracellular matrix abnormalities in testis and epididymis of XXSxr(“sex‐reversed”) mice

“…The epididymal head is also much less vascularized in the pseudomale than in the normal male (LeBarr and Blecher, 1987). Electron microscopic studies revealed ultrastructural abnormalities in both the pseudomale testis and epididymis (Wilkinson et al, 1988). Instead of normal, organized collagen fibres, thin, "wispy" material was detected, reflecting perhaps immature or poorly formed collagen molecules.…”