HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 71/5/1614    most recent biolreprod.104.029678v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feki, A. Articles by Irminger-Finger, I. Search for Related Content PubMed PubMed Citation Articles by Feki, A. Articles by Irminger-Finger, I. Agricola Articles by Feki, A. Articles by Irminger-Finger, I.

BARD1 Expression During Spermatogenesis Is Associated with Apoptosis and Hormonally Regulated¹

Biology of Aging Laboratory,³ Department of Geriatrics, Department of Gynecology and Obstetrics,⁴ University Hospitals, CH-12225 Geneva, Switzerland INSERM-INRA U 418,⁵ Hôpital Debrousse, Lyon, 69322 Cedex 05, France Institut de Biologie,⁶ INSERM, U419 Nantes, France

The BRCA1-binding RING-finger domain protein BARD1 may act conjointly with BRCA1 in DNA repair and in ubiquitination, but it may also induce apoptosis in a BRCA1-independent manner. In this study, we have investigated BARD1 expression during spermatogenesis. In contrast with BRCA1, which is expressed only in meiotic spermatocytes and early round spermatids, BARD1 is expressed during all stages of spermatogenesis. However, while spermatogonia expressed full-length BARD1 mRNA, later stages of spermatocyte precursors express predominantly a novel, shorter splice form BARD1ß. BARD1ß lacks the BRCA1-interacting RING finger but maintains its proapoptotic activity. Consistently, BRCA1 can counteract the proapoptotic activity of full-length BARD1 but not of BARD1ß. Several lines of evidence suggest that BARD1 is involved in proapoptotic signaling in testis: i) both BARD1 isoforms are mostly found in cells that stain positive for TUNEL, Bax, and activated caspase 3; ii) BARD1ß, capable of inducing apoptosis even in the presence of BRCA1, is specifically expressed in BRCA1-positive later stages of spermatogenesis; iii) antiapoptotic hormonal stimulation leads to BARD1 downregulation; and iv) BARD1 expression is associated with human pathologies causing sterility due to increased germ cell death. Our data suggest that full-length BARD1 might be involved in apoptotic control in spermatogonia and primary spermatocytes, while a switch to the BRCA1-independent BARD1ß might be necessary to induce apoptosis in BRCA1-expressing meiotic spermatocytes and early round spermatids.

¹ Supported by focused giving grant from Johnson and Johnson and Swiss National Science Foundation grant to I.I.F.

² Correspondence: Irmgard Irminger-Finger, Biology of Aging Laboratory, Department of Geriatrics, University of Geneva, 2 ch. Petit-Bel-Air, 1225 Chene-Bourg/Geneva, Switzerland. FAX: 41 22 305 5455; irmgard.irminger{at}medecine.unige.ch

This article has been cited by other articles:

				K. A. Thasni, S. Rakesh, G. Rojini, T. Ratheeshkumar, G. Srinivas, and S. Priya Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents Ann. Onc., April 1, 2008; 19(4): 696 - 705. [Abstract] [Full Text] [PDF]

				L. Li, S. Ryser, E. Dizin, D. Pils, M. Krainer, C. E. Jefford, F. Bertoni, R. Zeillinger, and I. Irminger-Finger Oncogenic BARD1 Isoforms Expressed in Gynecological Cancers Cancer Res., December 15, 2007; 67(24): 11876 - 11885. [Abstract] [Full Text] [PDF]

				A. E. Falender, R. N. Freiman, K. G. Geles, K. C. Lo, K. Hwang, D. J. Lamb, P. L. Morris, R. Tjian, and J. S. Richards Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID Genes & Dev., April 1, 2005; 19(7): 794 - 803. [Abstract] [Full Text] [PDF]