| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Reproductive Biology Unit (J.-M.K., B.K.T.), Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa; and the Hormones, Growth and Development Unit, Loeb Health Research Institute (J.-M.K., B.K.T.), Ottawa, Ontario, Canada K1Y 4E9; and the Department of Biology (Y.-D.Y.), College of Natural Sciences, Hanyang University, Seoul 133–791, Korea
Address all correspondence and requests for reprints to: Dr. Benjamin K. Tsang, Reproductive Biology Unit, Department of Obstetrics and Gynecology, The Ottawa Hospital (Civic Site), 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9. E-mail: btsang{at}lri.ca
In the present study we have examined the presence of Fas, Fas ligand (FasL), and p53 in rat granulosa cells during follicular development and atresia, especially in relation to the granulosa cell cycle progression and the onset of granulosa cell apoptosis. Fas, FasL, and p53 proteins were immunolocalized, and their contents were determined by Western blotting. Granulosa cell apoptosis was assessed by DNA fragmentation analyses (DNA ladder) and in situ terminal deoxynucleotidyl transferase mediated deoxy-UTP-biotin nick end labeling (TUNEL) as well as by flow cytometry. Ovaries not exposed to gonadotropins (control) consisted predominantly of preantral and early (small) antral follicles, the latter of which were mostly atretic and demonstrated intense TUNEL staining in granulosa cells exhibiting positive immunoreactivities for FasL and Fas. Granulosa cells isolated from these follicles were apoptotic, as evident by clear ladder pattern of DNA fragmentation upon electrophoretic analysis and the high percentage (>10%) of the cell population in the A0 phase of the cell cycle. After gonadotropin treatment, these features completely disappeared during each of the 3 days of follicular growth to the medium to large antral stages. Cell cycle analysis showed significantly higher proportion of the cells in S and G2/M phases compared with controls, which was accompanied by marked decrease in immunoreactivities for Fas, FasL, and p53. By days 4 and 5, widespread atresia and extensive granulosa cell apoptosis were noted in large antral and preovulatory follicles and were coincidental to increased expression of p53 and Fas, but not of FasL, as well as an apparent arrest of granulosa cell G1/S progression, as evident by an increased cell population in G0/G1 and a decrease in the S and G2/M. Granulosa cells from equine CG-primed ovaries exhibited marked increases in p53 and Fas protein contents and apoptosis after adenoviral p53-sense complementary DNA infection in vitro and were more responsive to Fas activation by an agonistic Fas monoclonal antibody challenge. Taken together, these findings are consistent with the well accepted concept that gonadotropin plays a central role as a survival factor in the regulation of granulosa cell Fas/FasL and p53 expression during ovarian follicular development. In addition, the control of granulosa cell apoptosis may involve two consecutive cellular/molecular events: cell cycle arrest at G1/S and exit from G0 into A0 phase, via regulation of the p53 and Fas/FasL death pathways.
This article has been cited by other articles:
 |
|
 |
|
  A. M. Orimoto, K. Dumaresq-Doiron, J.-Y. Jiang, N. Tanphaichitr, B. K. Tsang, and E. Carmona Mammalian Hyaluronidase Induces Ovarian Granulosa Cell Apoptosis and Is Involved in Follicular Atresia Endocrinology, November 1, 2008; 149(11): 5835 - 5847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Parborell, D. Abramovich, and M. Tesone Intrabursal Administration of the Antiangiopoietin 1 Antibody Produces a Delay in Rat Follicular Development Associated with an Increase in Ovarian Apoptosis Mediated by Changes in the Expression of BCL2 Related Genes Biol Reprod, March 1, 2008; 78(3): 506 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Abramovich, F. Parborell, and M. Tesone Effect of a Vascular Endothelial Growth Factor (VEGF) Inhibitory Treatment on the Folliculogenesis and Ovarian Apoptosis in Gonadotropin-Treated Prepubertal Rats Biol Reprod, September 1, 2006; 75(3): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A Slot, M. Voorendt, M. de Boer-Brouwer, H. H van Vugt, and K. J Teerds Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary J. Endocrinol., February 1, 2006; 188(2): 179 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Hussein Apoptosis in the ovary: molecular mechanisms Hum. Reprod. Update, March 1, 2005; 11(2): 162 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chen, T. Yano, H. Matsumi, Y. Osuga, N. Yano, J. Xu, O. Wada, K. Koga, T. Fujiwara, K. Kugu, et al. Cross-Talk between Fas/Fas Ligand System and Nitric Oxide in the Pathway Subserving Granulosa Cell Apoptosis: A Possible Regulatory Mechanism for Ovarian Follicle Atresia Endocrinology, February 1, 2005; 146(2): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cherian-Shaw, R. Das, C. A. VandeVoort, and C. L. Chaffin Regulation of Steroidogenesis by p53 in Macaque Granulosa Cells and H295R Human Adrenocortical Cells Endocrinology, December 1, 2004; 145(12): 5734 - 5744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Laoag-Fernandez, H. Matsuo, H. Murakoshi, A. L. Hamada, B. K. Tsang, and T. Maruo 3,5,3'-Triiodothyronine Down-Regulates Fas and Fas Ligand Expression and Suppresses Caspase-3 and Poly (Adenosine 5'-Diphosphate-Ribose) Polymerase Cleavage and Apoptosis in Early Placental Extravillous Trophoblasts in Vitro J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4069 - 4077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Hamm, G. K. Bhat, W. E. Thompson, and D. R. Mann Folliculogenesis Is Impaired and Granulosa Cell Apoptosis Is Increased in Leptin-Deficient Mice Biol Reprod, July 1, 2004; 71(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Thompson, E. Asselin, A. Branch, J. K. Stiles, P. Sutovsky, L. Lai, G.-S. Im, R. S. Prather, S. C. Isom, E. Rucker III, et al. Regulation of Prohibitin Expression During Follicular Development and Atresia in the Mammalian Ovary Biol Reprod, July 1, 2004; 71(1): 282 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.T. Bridgham and A.L. Johnson Alternatively Spliced Variants of Gallus gallus TNFRSF23 Are Expressed in the Ovary and Differentially Regulated by Cell Signaling Pathways Biol Reprod, April 1, 2004; 70(4): 972 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Hu, R. G. Cowan, R. M. Harman, and S. M. Quirk Cell Cycle Progression and Activation of Akt Kinase Are Required for Insulin-Like Growth Factor I-Mediated Suppression of Apoptosis in Granulosa Cells Mol. Endocrinol., February 1, 2004; 18(2): 326 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Quirk, R. G. Cowan, R. M. Harman, C.-L. Hu, and D. A. Porter Ovarian follicular growth and atresia: The relationship between cell proliferation and survival J Anim Sci, January 1, 2004; 82(13_suppl): E40 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.M. Perks, P.V. Newcomb, M. Grohmann, R.J. Wright, H.D. Mason, and J.M.P. Holly Prolactin acts as a potent survival factor against C2-ceramide-induced apoptosis in human granulosa cells Hum. Reprod., December 1, 2003; 18(12): 2672 - 2677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Depalo, L. Nappi, G. Loverro, S. Bettocchi, M. L. Caruso, A. M. Valentini, and L. Selvaggi Evidence of apoptosis in human primordial and primary follicles Hum. Reprod., December 1, 2003; 18(12): 2678 - 2682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, P. U. Rippstein, and B. K. Tsang Role and Gonadotrophic Regulation of X-Linked Inhibitor of Apoptosis Protein Expression During Rat Ovarian Follicular Development In Vitro Biol Reprod, February 1, 2003; 68(2): 610 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sapi, W. D. Brown, S. Aschkenazi, C. Lim, A. Munoz, B. M. Kacinski, T. Rutherford, and G. Mor Regulation of Fas Ligand Expression By Estrogen in Normal Ovary Reproductive Sciences, July 1, 2002; 9(4): 243 - 250. [Abstract] [PDF]
|
|
|
|
|
|
Y. Wang, S. Chan, and B. K. Tsang Involvement of Inhibitory Nuclear Factor-{kappa}B (NF{kappa}B)-Independent NF{kappa}B Activation in the Gonadotropic Regulation of X-Linked Inhibitor of Apoptosis Expression during Ovarian Follicular Development in Vitro Endocrinology, July 1, 2002; 143(7): 2732 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Embree-Ku and K. Boekelheide Absence of p53 and FasL Has Sexually Dimorphic Effects on Both Development and Reproduction Experimental Biology and Medicine, July 1, 2002; 227(7): 545 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Manikkam, Y. Li, B. M. Mitchell, D. E. Mason, and L. C. Freeman Potassium Channel Antagonists Influence Porcine Granulosa Cell Proliferation, Differentiation, and Apoptosis Biol Reprod, July 1, 2002; 67(1): 88 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, E. Asselin, and B. K. Tsang Involvement of Transforming Growth Factor {alpha} in the Regulation of Rat Ovarian X-Linked Inhibitor of Apoptosis Protein Expression and Follicular Growth by Follicle-Stimulating Hormone Biol Reprod, June 1, 2002; 66(6): 1672 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Richards, S. C. Sharma, A. E. Falender, and Y. H. Lo Expression of FKHR, FKHRL1, and AFX Genes in the Rodent Ovary: Evidence for Regulation by IGF-I, Estrogen, and the Gonadotropins Mol. Endocrinol., March 1, 2002; 16(3): 580 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hasan, G. Hosseini, M. Princivalle, J.-C. Dong, D. Birsan, C. Cagide, and A. I. de Agostini Coordinate Expression of Anticoagulant Heparan Sulfate Proteoglycans and Serine Protease Inhibitors in the Rat Ovary: A Potent System of Proteolysis Control Biol Reprod, January 1, 2002; 66(1): 144 - 158. [Abstract] [Full Text]
|
|
|
|
|
|
A. Gruslin, Q. Qiu, and B. K. Tsang Influence of Maternal Smoking on Trophoblast Apoptosis Throughout Development: Possible Involvement of Xiap Regulation Biol Reprod, October 1, 2001; 65(4): 1164 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.T. Bridgham and A.L. Johnson Expression and Regulation of Fas Antigen and Tumor Necrosis Factor Receptor Type I in Hen Granulosa Cells Biol Reprod, September 1, 2001; 65(3): 733 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Hu, R. G. Cowan, R. M. Harman, D. A. Porter, and S. M. Quirk Apoptosis of Bovine Granulosa Cells After Serum Withdrawal Is Mediated by Fas Antigen (CD95) and Fas Ligand Biol Reprod, February 1, 2001; 64(2): 518 - 526. [Abstract] [Full Text]
|
|
|
|
|
|
A. L.L. Durlinger, P. Kramer, B. Karels, J.A. Grootegoed, J. Th.J. Uilenbroek, and A. P.N. Themmen Apoptotic and proliferative changes during induced atresia of pre-ovulatory follicles in the rat Hum. Reprod., December 1, 2000; 15(12): 2504 - 2511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.J. Devine, C.M. Payne, M.K. McCuskey, and P.B. Hoyer Ultrastructural Evaluation of Oocytes During Atresia in Rat Ovarian Follicles Biol Reprod, November 1, 2000; 63(5): 1245 - 1252. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Quirk, R. M. Harman, and R. G. Cowan Regulation of Fas Antigen (Fas, CD95)-Mediated Apoptosis of Bovine Granulosa Cells by Serum and Growth Factors Biol Reprod, November 1, 2000; 63(5): 1278 - 1284. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Sasaki, Y. Sheng, F. Kotsuji, and B. K. Tsang Down-Regulation of X-linked Inhibitor of Apoptosis Protein Induces Apoptosis in Chemoresistant Human Ovarian Cancer Cells Cancer Res., October 1, 2000; 60(20): 5659 - 5666. [Abstract] [Full Text]
|
|
|
|
|
|
A. Makrigiannakis, K. Amin, G. Coukos, J. L. Tilly, and C. Coutifaris Regulated Expression and Potential Roles of p53 and Wilms' Tumor Suppressor Gene (WT1) during Follicular Development in the Human Ovary J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 449 - 459. [Abstract] [Full Text]
|
|
| 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 |
