Regulatory role of p27(kip1) in the mouse and human testis

Tim L. Beumer*, Hiroaki Kiyokawa, Hermien L. Roepers-Gajadien, Linda A C Van Den Bos, Tycho M T W Lock, Iris S. Gademan, Derk H. Rutgers, Andrew Koff, Dirk G. De Rooij

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

p27(kip1) is a cyclin-dependent kinase inhibitor that regulates the G'1/S transition of the cell cycle. Immunohistochemical analysis showed that during mouse testicular development p27(kip1) is induced when the fetal germ cells, gonocytes, become quiescent on day 16 postcoitum, suggesting that p27(kip1) is an important factor for the G1/G0 arrest in gonocytes. In the adult mouse and human testis, in general, spermatogonia are proliferating actively, except for undifferentiated spermatogonia that also go through a long G1/G0 arrest. However, none of the different types of germ cells immunohistochemically stained for p27(kip1). During development, Sertoli cells are proliferating actively and only occasionally were lightly p27(kip1) stained Sertoli cells observed. In contrast, in the adult testis the terminally differentiated Sertoli cells heavily stain for p27(kip1). Twenty to 30% of both fetal and adult type Leydig cells lightly stained for p27(kip1), possibly indicating the proportion of terminally differentiated cells in the Leydig cell population. In p27(kip1) knockout mice, aberrations in the spermatogenic process were observed. First, an increase in the numbers of A spermatogonia was found, and second, abnormal (pre)leptotene spermatocytes were observed, some of which seemingly tried to enter a mitotic division instead of entering the meiotic prophase. These observations indicate that p27(kip1) has a role in the regulation of spermatogonial proliferation, or apoptosis, and the onset of the meiotic prophase in preleptotene spermatocytes. However, as p27(kip1) is only expressed in Sertoli cells, the role of p27(kip1) in both spermatogonia and preleptotene spermatocytes must be indirect. Hence, part of the supportive and/or regulatory role of Sertoli cells in the spermatogenic process depends on the expression of p27(kip1) in these cells. Finally, we show that the expression of p27(kip1) transiently increases by a factor of 3 after irradiation in whole testicular lysates. Hence, p27(kip1) seems to be involved in the cellular response after DNA damage.

Original languageEnglish (US)
Pages (from-to)1834-1840
Number of pages7
JournalEndocrinology
Volume140
Issue number4
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Endocrinology

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