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Expression of c-KIT and its ligand, stem cell factor, in normal and subfertile human testicular tissue
J I Sandlow1, H L Feng, M B Cohen
1Department of Urology, University of Iowa, Iowa City 52242-1089, USA.
Abstract:
The c-KIT proto-oncogene encodes for a transmembrane receptor and is associated with maturation of several cell types, including germ cells. The ligand of the receptor has been identified as stem cell factor (SCF). Loss or alteration of the expression of either of these factors leads to anemia, albinism, and/or sterility in mice. We examined the expression of c-KIT and SCF by immunohistochemistry in specimens from normal and infertile human testis. All specimens were obtained in the evaluation of male subfertility. We were able to demonstrate staining for c-KIT in Leydig cells in all specimens. Normal testis stained for c-KIT in the cytoplasm of early spermatogenic cells, as well as the acrosomal granules of the round spermatids and the acrosome of testicular spermatozoa. However, staining in testis demonstrating maturation arrest failed to demonstrate acrosomal staining, and Sertoli-only specimens demonstrated staining for c-KIT in Leydig cells only. The results for SCF demonstrated an overall uniform staining of Leydig cells in all specimens. The intensity of staining of Sertoli cells increased from normal to maturation arrest to Sertoli-only specimens. Germ cell staining was consistently negative. We hypothesize that these staining patterns for SCF are due to either lack of staining of the receptor-ligand complex or overexpression of the kit ligand in tissue that does not express the kit receptor. It appears that the c-kit receptor is expressed in the acrosome of developing germ cells, as well as in Leydig cells and early spermatogenic cells, suggesting a role in the acrosome reaction, as well as germ cell maturation and differentiation.
Insights
The c-KIT receptor and stem cell factor (SCF) are crucial for male fertility. Their altered expression in the human testis is linked to infertility, particularly affecting germ cell maturation and acrosome development.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cell Biology
Background:
- The c-KIT proto-oncogene encodes a transmembrane receptor crucial for the maturation of various cell types, including germ cells.
- Stem cell factor (SCF) is the identified ligand for the c-KIT receptor.
- Alterations in c-KIT or SCF expression are associated with phenotypes such as anemia, albinism, and sterility in mice.
Purpose of the Study:
- To investigate the expression patterns of c-KIT and SCF in normal and infertile human testes.
- To correlate c-KIT and SCF expression with specific conditions of male subfertility, including maturation arrest and Sertoli-only syndromes.
Main Methods:
- Immunohistochemistry was employed to detect c-KIT and SCF expression in testicular specimens.
- Specimens included normal testes and testes from patients evaluated for male subfertility.
Main Results:
- c-KIT was detected in Leydig cells of all specimens, early spermatogenic cells, and the acrosomal components of round spermatids and spermatozoa in normal testes.
- Acrosomal staining for c-KIT was absent in cases of maturation arrest; Sertoli-only specimens showed c-KIT in Leydig cells only.
- SCF exhibited uniform staining in Leydig cells across all specimens, with increased staining intensity in Sertoli cells from normal to maturation arrest to Sertoli-only conditions. Germ cell staining for SCF was consistently negative.
Conclusions:
- The c-KIT receptor appears to play a role in the acrosome reaction, germ cell maturation, and differentiation, with its expression localized in the acrosome of developing germ cells, Leydig cells, and early spermatogenic cells.
- Observed SCF staining patterns may result from either a lack of receptor-ligand complex staining or overexpression of SCF in tissues lacking the c-KIT receptor.
- Aberrant expression patterns of c-KIT and SCF in the human testis are associated with male infertility, particularly impacting germ cell development and maturation.