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Molecular Human Reproduction, Vol. 6, No. 11, 967-972, November 2000
© 2000 European Society of Human Reproduction and Embryology


Testis and spermatogenesis

CREM activator and repressor isoforms in human testis: sequence variations and inaccurate splicing during impaired spermatogenesis

R. Behr1 and G.F. Weinbauer2,3

Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Münster, Germany

Abstract

cAMP responsive element modulator (CREM) activators are specifically expressed in haploid germ cells prior to cell elongation and are essential for spermatid development in mice. Recent studies indicate that CREM activators are also involved in the process of spermatid maturation in men. Unlike the activators, CREM repressors were suggested to be absent from adult mouse and dog testes. The present work investigates CREM transcripts in human testis with normal (n = 4) and impaired spermatogenesis (n = 2). Two activator transcripts could be identified corresponding to the {tau}2 isoform with and without exon {gamma}. Interestingly, four CREM repressors could be isolated from specimens with complete spermatogenesis. These were {gamma}-repressor (exons B, E, F, H, Ib), CREM {Delta}C-F, ß (exons B, G, H, Ib), CREM {Delta}C-G, ß (exons B, H, Ib), and CREM {Delta}C-G, {alpha} (exons B, H, Ia, Ib). These isoforms were also present in cynomolgus monkey testes. A novel CREM splice variant (CREM {Delta}C-H) was detected in a specimen with spermatid maturation defect. Beyond that, inaccurate CREM splicing, giving rise to inactive transcripts, was encountered in a specimen with impaired spermatogenesis. In conclusion, several CREM repressor transcripts are present in adult human testes, and altered transcript splicing is associated with impaired spermatogenesis.

CREM/human/infertility/spermatogenesis/splicing

Notes

1 Present addresses: University of Pennsylvania School of Medicine, Department of Genetics, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104-6145, USA,

2 Covance Laboratories GmbH, Kesselfeld 29, D-48163 Münster, Germany

3 To whom correspondence should be addressed. E-mail: gerhard.weinbauer{at}covance.com


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