help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rucker, E. B.
Right arrow Articles by Hennighausen, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rucker, E. B., III
Right arrow Articles by Hennighausen, L.
Molecular Endocrinology 14 (7):1038
Copyright © 2000 by The Endocrine Society

Bcl-x and Bax Regulate Mouse Primordial Germ Cell Survival and Apoptosis during Embryogenesis

Edmund B. Rucker, III, Patricia Dierisseau, Kay-Uwe Wagner, Lisa Garrett, Anthony Wynshaw-Boris1, Jodi A. Flaws and Lothar Hennighausen

Laboratory of Genetics and Physiology (E.B.R., P.D., K.-U.W., L.H.) National Institute of Diabetes, Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland 20892
Genetic Disease Research Branch (L.G., A.W.-B.) National Human Genome Research Institute National Institutes of Health Bethesda, Maryland 20892
Department of Epidemiology and Preventive Medicine (J.A.F.) University of Maryland School of Medicine Baltimore, Maryland 21201

Restricted germ cell loss through apoptosis is initiated in the fetal gonad around embryonic day 13.5 (E13.5) as part of normal germ cell development. The mechanism of this germ cell attrition is unknown. We show that Bcl-x plays a crucial role in maintaining the survival of mouse germ cells during gonadogenesis. A bcl-x hypomorphic mouse was generated through the introduction of a neomycin (neo) gene into the promoter of the bcl-x gene by homologous recombination. Mice that contained two copies of the hypomorphic allele had severe reproductive defects attributed to compromised germ cell development. Males with two mutant alleles lacked spermatogonia and were sterile; females showed a severely reduced population of primordial and primary follicles and exhibited greatly impaired fertility. Primordial germ cells (PGCs) in bcl-x hypomorph mice migrated to the genital ridge by E12.5 but were depleted by E15.5, a time when Bcl-x and Bax were present. Two additional bcl-x transcripts were identified in fetal germ cells more than 300 bp upstream of previously reported start sites. Insertion of a neo cassette led to a down-regulation of the bcl-x gene at E12.5 in the hypomorph. Bax was detected by immunohistochemistry in germ cells from bcl-x hypomorph and control testes at E12.5 and E13.5. Bcl-x function was restored, and animals of both genders were fertile after removal of the neo selection cassette using Cre-mediated recombination. Alternatively, the loss of Bcl-x function in the hypomorph was corrected by the deletion of both copies of the bax gene, resulting in a restoration of germ cell survival. These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis.




This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
H. Kim, T. Nakajima, S. Hayashi, P. Chambon, H. Watanabe, T. Iguchi, and T. Sato
Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries
Biol Reprod, November 1, 2009; 81(5): 1002 - 1009.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. A. Edson, A. K. Nagaraja, and M. M. Matzuk
The Mammalian Ovary from Genesis to Revelation
Endocr. Rev., October 1, 2009; 30(6): 624 - 712.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
E. M. Carrington, M. D. McKenzie, E. Jansen, M. Myers, S. Fynch, C. Kos, A. Strasser, T. W. Kay, C. L. Scott, and J. Allison
Islet {beta}-Cells Deficient in Bcl-xL Develop but Are Abnormally Sensitive to Apoptotic Stimuli
Diabetes, October 1, 2009; 58(10): 2316 - 2323.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. M. Tingen, S. K. Bristol-Gould, S. E. Kiesewetter, J. T. Wellington, L. Shea, and T. K. Woodruff
Prepubertal Primordial Follicle Loss in Mice Is Not Due to Classical Apoptotic Pathways
Biol Reprod, July 1, 2009; 81(1): 16 - 25.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. Ge, M. Yu, J. N. Petitte, and C. Zhang
Epidermal Growth Factor-Induced Proliferation of Chicken Primordial Germ Cells: Involvement of Calcium/Protein Kinase C and NFKB1
Biol Reprod, March 1, 2009; 80(3): 528 - 536.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
R. S. Akhtar, B. J. Klocke, A. Strasser, and K. A. Roth
Loss of BH3-only Protein Bim Inhibits Apoptosis of Hemopoietic Cells in the Fetal Liver and Male Germ Cells but Not Neuronal Cells in Bcl-x-deficient Mice
J. Histochem. Cytochem., October 1, 2008; 56(10): 921 - 927.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Oshima, T. Akiyama, A. Hikita, M. Iwasawa, Y. Nagase, M. Nakamura, H. Wakeyama, N. Kawamura, T. Ikeda, U.-i. Chung, et al.
Pivotal Role of Bcl-2 Family Proteins in the Regulation of Chondrocyte Apoptosis
J. Biol. Chem., September 26, 2008; 283(39): 26499 - 26508.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Y. Choi, D. J. Ballow, Y. Xin, and A. Rajkovic
Lim Homeobox Gene, Lhx8, Is Essential for Mouse Oocyte Differentiation and Survival
Biol Reprod, September 1, 2008; 79(3): 442 - 449.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. G. Harb, B. I. Chyla, and C. S. Huettner
Loss of Bcl-x in Ph+ B-ALL increases cellular proliferation and does not inhibit leukemogenesis
Blood, April 1, 2008; 111(7): 3760 - 3769.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y.-Z. Le, W. Zheng, P.-C. Rao, L. Zheng, R. E. Anderson, N. Esumi, D. J. Zack, and M. Zhu
Inducible Expression of Cre Recombinase in the Retinal Pigmented Epithelium
Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1248 - 1253.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
A M Lobascio, F G Klinger, M L Scaldaferri, D Farini, and M De Felici
Analysis of programmed cell death in mouse fetal oocytes
Reproduction, August 1, 2007; 134(2): 241 - 252.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
C. R Greenfeld, M. E Pepling, J. K Babus, P. A Furth, and J. A Flaws
BAX regulates follicular endowment in mice
Reproduction, May 1, 2007; 133(5): 865 - 876.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Alton and T. Taketo
Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries
J. Cell Sci., February 1, 2007; 120(3): 417 - 424.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. Runyan, K. Schaible, K. Molyneaux, Z. Wang, L. Levin, and C. Wylie
Steel factor controls midline cell death of primordial germ cells and is essential for their normal proliferation and migration
Development, December 15, 2006; 133(24): 4861 - 4869.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Zheng, R. E. Anderson, M.-P. Agbaga, E. B. Rucker III, and Y.-Z. Le
Loss of BCL-XL in Rod Photoreceptors: Increased Susceptibility to Bright Light Stress
Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5583 - 5589.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws
Ovarian follicle development and transgenic mouse models
Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. F. Vitiello, R. J. Staversky, S. C. Gehen, C. J. Johnston, J. N. Finkelstein, T. W. Wright, and M. A. O'Reilly
p21Cip1 Protection against Hyperoxia Requires Bcl-XL and Is Uncoupled from Its Ability to Suppress Growth
Am. J. Pathol., June 1, 2006; 168(6): 1838 - 1847.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
R G Lea, L P Andrade, M T Rae, L T Hannah, C E Kyle, J F Murray, S M Rhind, and D W Miller
Effects of maternal undernutrition during early pregnancy on apoptosis regulators in the ovine fetal ovary
Reproduction, January 1, 2006; 131(1): 113 - 124.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
D. Baron, R. Houlgatte, A. Fostier, and Y. Guiguen
Large-Scale Temporal Gene Expression Profiling During Gonadal Differentiation and Early Gametogenesis in Rainbow Trout
Biol Reprod, November 1, 2005; 73(5): 959 - 966.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
H. S. Kok, K. M. van Asselt, Y. T. van der Schouw, P. H.M. Peeters, and C. Wijmenga
Genetic studies to identify genes underlying menopausal age
Hum. Reprod. Update, September 1, 2005; 11(5): 483 - 493.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. M. Savitt, S. S. Jang, W. Mu, V. L. Dawson, and T. M. Dawson
Bcl-x Is Required for Proper Development of the Mouse Substantia Nigra
J. Neurosci., July 20, 2005; 25(29): 6721 - 6728.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Zhang, Y.-b. Chen, J. M. Hardwick, M. I. Miller, C. Plachez, L. J. Richards, P. Yarowsky, P. van Zijl, and S. Mori
Magnetic Resonance Diffusion Tensor Microimaging Reveals a Role for Bcl-x in Brain Development and Homeostasis
J. Neurosci., February 23, 2005; 25(8): 1881 - 1888.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Hon, E. B. Rucker III, L. Hennighausen, and J. Jacob
bcl-xL Is Critical for Dendritic Cell Survival In Vivo
J. Immunol., October 1, 2004; 173(7): 4425 - 4432.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. Tomic, K. P. Miller, H. A. Kenny, T. K. Woodruff, P. Hoyer, and J. A. Flaws
Ovarian Follicle Development Requires Smad3
Mol. Endocrinol., September 1, 2004; 18(9): 2224 - 2240.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
M Myers, K L Britt, N G M Wreford, F J P Ebling, and J B Kerr
Methods for quantifying follicular numbers within the mouse ovary
Reproduction, May 1, 2004; 127(5): 569 - 580.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
S. Cayli, D. Sakkas, L. Vigue, R. Demir, and G. Huszar
Cellular maturity and apoptosis in human sperm: creatine kinase, caspase-3 and Bcl-XL levels in mature and diminished maturity sperm
Mol. Hum. Reprod., May 1, 2004; 10(5): 365 - 372.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Stallock, K. Molyneaux, K. Schaible, C. M. Knudson, and C. Wylie
The pro-apoptotic gene Bax is required for the death of ectopic primordial germ cells during their migration in the mouse embryo
Development, December 29, 2003; 130(26): 6589 - 6597.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. H. Burns, G. E. Owens, S. C. Ogbonna, J. H. Nilson, and M. M. Matzuk
Expression Profiling Analyses of Gonadotropin Responses and Tumor Development in the Absence of Inhibins
Endocrinology, October 1, 2003; 144(10): 4492 - 4507.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
W. Yan, J.-X. Huang, A.-S. Lax, L. Pelliniemi, E. Salminen, M. Poutanen, and J. Toppari
Overexpression of Bcl-w in the Testis Disrupts Spermatogenesis: Revelation of a Role of BCL-W in Male Germ Cell Cycle Control
Mol. Endocrinol., September 1, 2003; 17(9): 1868 - 1879.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
D.N. Modi, S. Sane, and D. Bhartiya
Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads
Mol. Hum. Reprod., April 1, 2003; 9(4): 219 - 225.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Takai, J. Canning, G. I. Perez, J. K. Pru, J. J. Schlezinger, D. H. Sherr, R. N. Kolesnick, J. Yuan, R. A. Flavell, S. J. Korsmeyer, et al.
Bax, Caspase-2, and Caspase-3 Are Required for Ovarian Follicle Loss Caused by 4-Vinylcyclohexene Diepoxide Exposure of Female Mice in Vivo
Endocrinology, January 1, 2003; 144(1): 69 - 74.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. E. Orwig, B.-Y. Ryu, M. R. Avarbock, and R. L. Brinster
Male germ-line stem cell potential is predicted by morphology of cells in neonatal rat testes
PNAS, September 3, 2002; 99(18): 11706 - 11711.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
L. D. Russell, H. Chiarini-Garcia, S. J. Korsmeyer, and C. M. Knudson
Bax-Dependent Spermatogonia Apoptosis Is Required for Testicular Development and Spermatogenesis
Biol Reprod, April 1, 2002; 66(4): 950 - 958.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. M. Matikainen, T. Moriyama, Y. Morita, G. I. Perez, S. J. Korsmeyer, D. H. Sherr, and J. L. Tilly
Ligand Activation of the Aromatic Hydrocarbon Receptor Transcription Factor Drives Bax-Dependent Apoptosis in Developing Fetal Ovarian Germ Cells
Endocrinology, February 1, 2002; 143(2): 615 - 620.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
G. Riedlinger, R. Okagaki, K.-U. Wagner, E. B. Rucker III, T. Oka, K. Miyoshi, J. A. Flaws, and L. Hennighausen
Bcl-x Is Not Required for Maintenance of Follicles and Corpus Luteum in the Postnatal Mouse Ovary
Biol Reprod, February 1, 2002; 66(2): 438 - 444.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. K. Pru and J. L. Tilly
Programmed Cell Death in the Ovary: Insights and Future Prospects Using Genetic Technologies
Mol. Endocrinol., June 1, 2001; 15(6): 845 - 853.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. S. Richards
Perspective: The Ovarian Follicle--A Perspective in 2001
Endocrinology, June 1, 2001; 142(6): 2184 - 2193.
[Full Text] [PDF]

Home page
 DevelopmentHome page
K. Wagner, E Claudio, E. Rucker, G Riedlinger, C Broussard, P. Schwartzberg, U Siebenlist, and L Hennighausen
Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly
Development, January 11, 2000; 127(22): 4949 - 4958.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society