Testicular cAMP responsive element modulator (CREM) protein is expressed in round spermatids but is absent or reduced in men with round spermatid maturation arrest.
Mice lacking the functional cAMP responsive element modulator (CREM) gene, a component of cAMP-mediated signal transduction, exhibit a specific arrest of round spermatid development although follicle stimulating hormone (FSH) and androgen secretion are not impaired. We studied testicular expression of CREM protein by immunocytochemistry in four patients with complete spermatogenesis (obstructive azoospermia), in 20 infertile patients with round spermatid maturation arrest (n = 10) or mixed atrophy (n = 10) and in six prostate cancer patients undergoing orchidectomy. Concentrations of testosterone were below normal in three patients. Concentrations of luteinizing hormone (LH) were lowered in two patients and elevated in one patient. FSH concentrations were above normal in ten patients. During normal spermatogenesis, CREM was expressed in nuclei of round spermatids in stages I-III of spermatogenesis but not in elongating spermatids. Western blot analysis of testes from prostate cancer patients indicated a major CREM band of approximately 35 kDa. Among patients with predominant round spermatid maturation arrest, CREM expression was significantly reduced (P < 0.05) or undetectable as revealed by quantitative image analysis. CREM-negative spermatids failed to progress beyond stage III of spermatogenesis. Our observations suggest a role for CREM in human spermatid development and raise the possibility that altered CREM expression could be associated with spermatid maturation defects in some cases of idiopathic male infertility.
Weinbauer
G F
GF
Institute of Reproductive Medicine of the University, Münster, Germany.
Behr
R
R
Bergmann
M
M
Nieschlag
E
E
D000293:Adolescent; D000328:Adult; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000032:analysis*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000378:metabolism*; D012097:Repressor Proteins; D013087:Spermatids / Q000737:chemistry*; D013091:Spermatogenesis; D013737:Testis / Q000737:chemistry
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator