Taking control of the female fertile lifespan: a key role for Bcl-2 family proteins
Seng H. Liew A , Kavitha Vaithiyanathan A B and Karla J. Hutt A B C
+ Author Affiliations
- Author Affiliations
A MIMR-PHI Institute of Medical Research, Clayton, Vic. 3168, Australia.
B Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic. 3800, Australia.
C Corresponding author. Email: karla.hutt@mimr-phi.org
Reproduction, Fertility and Development 28(7) 864-871 https://doi.org/10.1071/RD14326
Submitted: 2 September 2014 Accepted: 27 October 2014 Published: 26 November 2014
Abstract
Precisely how the length of the female fertile lifespan is regulated is poorly understood and it is likely to involve complex factors, one of which is follicle number. Indeed, the duration of female fertility appears to be intimately linked to the number of available oocytes, which are stored in the ovary as primordial follicles. There is mounting evidence implicating the intrinsic apoptosis pathway, which is controlled by members of the B-cell lymphoma-2 (BCL-2) family, as a key regulator of the number of primordial follicles established in the ovary at birth and maintained throughout reproductive life. Consequently, the pro- and anti-apoptotic BCL-2 family proteins are emerging as key determinants of the length of the female fertile lifespan. This review discusses the relationship between the intrinsic apoptosis pathway, follicle number and length of the female fertile lifespan.
Additional keywords: apoptosis, BCL2- family proteins, BH3-only proteins, fertility, follicles, ovary, primordial follicles.
References
Adams, J. M., and Cory, S. (1998). The Bcl-2 protein family: arbiters of cell survival. Science 281, 1322–1326.| The Bcl-2 protein family: arbiters of cell survival.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXlvVegsb8%3D&md5=7a7d19ed2df2b9edf9451529a396e643CAS | 9735050PubMed |
Adams, J. M., and Cory, S. (2007). The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26, 1324–1337.
| The Bcl-2 apoptotic switch in cancer development and therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitVKhsL8%3D&md5=b174db188591cdd0cbdf5d98a8aa0470CAS | 17322918PubMed |
Adrain, C., and Martin, S. J. (2001). The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem. Sci. 26, 390–397.
| The mitochondrial apoptosome: a killer unleashed by the cytochrome seas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXkt1Kht7o%3D&md5=9c28443d600f5c654de77aedc240ccd8CAS | 11406413PubMed |
Albamonte, M. S., Willis, M. A., Albamonte, M. I., Jensen, F., Espinosa, M. B., and Vitullo, A. D. (2008). The developing human ovary: immunohistochemical analysis of germ-cell-specific VASA protein, BCL-2/BAX expression balance and apoptosis. Hum. Reprod. 23, 1895–1901.
| The developing human ovary: immunohistochemical analysis of germ-cell-specific VASA protein, BCL-2/BAX expression balance and apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXoslGqurc%3D&md5=f2599ca6144f6b16ec46582f12aa0791CAS | 18534994PubMed |
Alton, M., and Taketo, T. (2007). Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries. J. Cell Sci. 120, 417–424.
| Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtlSkurk%3D&md5=a9c507a609ac9d29f4128d103f37c914CAS | 17213335PubMed |
Baker, T. G. (1971). Radiosensitivity of mammalian oocytes with particular reference to the human female. Am. J. Obstet. Gynecol. 110, 746–761.
| 1:STN:280:DyaE3M3mtl2gtA%3D%3D&md5=009fb119d0d75080e647e071d21cd0d9CAS | 4935165PubMed |
Bergeron, L., Perez, G. I., Macdonald, G., Shi, L., Sun, Y., Jurisicova, A., Varmuza, S., Latham, K. E., Flaws, J. A., Salter, J. C., Hara, H., Moskowitz, M. A., Li, E., Greenberg, A., Tilly, J. L., and Yuan, J. (1998). Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev. 12, 1304–1314.
| Defects in regulation of apoptosis in caspase-2-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjtVejsrc%3D&md5=76f0e62f8202003cc51fc33572679521CAS | 9573047PubMed |
Bristol-Gould, S. K., Kreeger, P. K., Selkirk, C. G., Kilen, S. M., Cook, R. W., Kipp, J. L., Shea, L. D., Mayo, K. E., and Woodruff, T. K. (2006). Postnatal regulation of germ cells by activin: the establishment of the initial follicle pool. Dev. Biol. 298, 132–148.
| Postnatal regulation of germ cells by activin: the establishment of the initial follicle pool.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpvFeksL4%3D&md5=aad640cf5c3749fc4d67e9f227deec32CAS | 16930587PubMed |
Byskov, A. G., Faddy, M. J., Lemmen, J. G., and Andersen, C. Y. (2005). Eggs forever? Differentiation 73, 438–446.
| Eggs forever?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtleksL3M&md5=28c5ef18555dee7ab8ced873c9d3f299CAS | 16351687PubMed |
Chun, S. Y., Billig, H., Tilly, J. L., Furuta, I., Tsafriri, A., and Hsueh, A. J. (1994). Gonadotropin suppression of apoptosis in cultured preovulatory follicles: mediatory role of endogenous insulin-like growth factor I. Endocrinology 135, 1845–1853.
| 1:CAS:528:DyaK2cXmvFeksbw%3D&md5=f52d0b1868dee2133a5af929667cb39eCAS | 7525255PubMed |
Cragg, M. S., Harris, C., Strasser, A., and Scott, C. L. (2009). Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat. Rev. Cancer 9, 321–326.
| Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjvF2gtLY%3D&md5=a05647f0b57b819b2c47957608fe157dCAS | 19343035PubMed |
De Felici, M., Di Carlo, A., Pesce, M., Iona, S., Farrace, M. G., and Piacentini, M. (1999). Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo. Cell Death Differ. 6, 908–915.
| Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXnt1CrtLw%3D&md5=317694e5835a565417212757a081c5e1CAS |
De Felici, M., Lobascio, A. M., and Klinger, F. G. (2008). Cell death in fetal oocytes: many players for multiple pathways. Autophagy 4, 240–242.
| Cell death in fetal oocytes: many players for multiple pathways.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXksFGru7o%3D&md5=b55e1741f8689719e672256d01f7ae17CAS | 18094606PubMed |
De Pol, A., Vaccina, F., Forabosco, A., Cavazzuti, E., and Marzona, L. (1997). Apoptosis of germ cells during human prenatal oogenesis. Hum. Reprod. 12, 2235–2241.
| Apoptosis of germ cells during human prenatal oogenesis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c%2Fmtlykuw%3D%3D&md5=a6d04dd49b6d411a3aed83771e926fe9CAS | 9402287PubMed |
Ene, A. C., Park, S., Edelmann, W., and Taketo, T. (2013). Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression. Dev. Biol. 377, 213–223.
| Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXjtl2jsLg%3D&md5=2bd4241e56bfc28b16bade8c8106f359CAS | 23384561PubMed |
Faddy, M. J. (2000). Follicle dynamics during ovarian ageing. Mol. Cell. Endocrinol. 163, 43–48.
| Follicle dynamics during ovarian ageing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXlvV2msro%3D&md5=a98935020e78749523323a2da8e1a82aCAS | 10963872PubMed |
Flaws, J. A., Hirshfield, A. N., Hewitt, J. A., Babus, J. K., and Furth, P. A. (2001). Effect of bcl-2 on the primordial follicle endowment in the mouse ovary. Biol. Reprod. 64, 1153–1159.
| Effect of bcl-2 on the primordial follicle endowment in the mouse ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXit1aru7w%3D&md5=5ff7727e2825370974e79d7f1762bea3CAS | 11259262PubMed |
Flaws, J. A., Marion, S. L., Miller, K. P., Christian, P. J., Babus, J. K., and Hoyer, P. B. (2006). Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4-vinylcyclohexene. Toxicol. Appl. Pharmacol. 215, 51–56.
| Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4-vinylcyclohexene.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xns1Glu78%3D&md5=a9571634935f7bbd8aaa17d21261fcd5CAS | 16631218PubMed |
Ghafari, F., Gutierrez, C. G., and Hartshorne, G. M. (2007). Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one. BMC Dev. Biol. 7, 87.
| Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one.Crossref | GoogleScholarGoogle Scholar | 17650311PubMed |
Gougeon, A. (1996). Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr. Rev. 17, 121–155.
| Regulation of ovarian follicular development in primates: facts and hypotheses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XislGisbc%3D&md5=48e5aec163c8db3e749674cb7a224530CAS | 8706629PubMed |
Greenfeld, C. R., Babus, J. K., Furth, P. A., Marion, S., Hoyer, P. B., and Flaws, J. A. (2007a). BAX is involved in regulating follicular growth, but is dispensable for follicle atresia in adult mouse ovaries. Reproduction 133, 107–116.
| BAX is involved in regulating follicular growth, but is dispensable for follicle atresia in adult mouse ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjs1aju70%3D&md5=0acf9e07b0b28150a50bdeb97b292e42CAS | 17244737PubMed |
Greenfeld, C. R., Pepling, M. E., Babus, J. K., Furth, P. A., and Flaws, J. A. (2007b). BAX regulates follicular endowment in mice. Reproduction 133, 865–876.
| BAX regulates follicular endowment in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotlGnurY%3D&md5=f077ac24ea8b8c71a7eba703dafc04b5CAS | 17616717PubMed |
Greenlee, R. T., Murray, T., Bolden, S., and Wingo, P. A. (2000). Cancer statistics, 2000. CA Cancer J. Clin. 50, 7–33.
| Cancer statistics, 2000.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7pvFWrug%3D%3D&md5=8f1de2c45f03e68406fbfff4f9d915ceCAS | 10735013PubMed |
Guigon, C. J., and Magre, S. (2006). Contribution of germ cells to the differentiation and maturation of the ovary: insights from models of germ cell depletion. Biol. Reprod. 74, 450–458.
| Contribution of germ cells to the differentiation and maturation of the ovary: insights from models of germ cell depletion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xhslejsrc%3D&md5=bddd80df6e791df0cc3b34b1a3141a53CAS | 16339043PubMed |
Hanoux, V., Pairault, C., Bakalska, M., Habert, R., and Livera, G. (2007). Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary. Cell Death Differ. 14, 671–681.
| Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjt1Sku7w%3D&md5=0bac8fe35b6978ef89ce3e59f12b9eaeCAS | 17082817PubMed |
Hirshfield, A. N. (1991). Development of follicles in the mammalian ovary. Int. Rev. Cytol. 124, 43–101.
| Development of follicles in the mammalian ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXlsFSmsr4%3D&md5=49fa99adfdb8340d2a0224e991383b6cCAS | 2001918PubMed |
Hotchkiss, R. S., Strasser, A., McDunn, J. E., and Swanson, P. E. (2009). Cell death. N. Engl. J. Med. 361, 1570–1583.
| Cell death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1OrurzP&md5=4d8fdf60ee5c82d5972b4a05ab461a17CAS | 19828534PubMed |
Hsu, S. Y., and Hsueh, A. J. (1998). Intracellular mechanisms of ovarian cell apoptosis. Mol. Cell. Endocrinol. 145, 21–25.
| Intracellular mechanisms of ovarian cell apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnt1eitrg%3D&md5=67aba93ee83f17c68ec318d7c719a472CAS | 9922095PubMed |
Hsu, S. Y., and Hsueh, A. J. (2000). Tissue-specific Bcl-2 protein partners in apoptosis: an ovarian paradigm. Physiol. Rev. 80, 593–614.
| 1:CAS:528:DC%2BD3cXisFShu7k%3D&md5=655c6230a67bf2b579192b430922fb11CAS | 10747202PubMed |
Hsu, S. Y., Lai, R. J., Finegold, M., and Hsueh, A. J. (1996). Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis. Endocrinology 137, 4837–4843.
| 1:CAS:528:DyaK28Xms1GjtLY%3D&md5=7e03dd812a5a88a05c7db456000388eaCAS | 8895354PubMed |
Hughes, F. M., and Gorospe, W. C. (1991). Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia. Endocrinology 129, 2415–2422.
| Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXmslOjs7c%3D&md5=5db1c09f9466e22b6b0de097e062711bCAS | 1935775PubMed |
Jablonka-Shariff, A., Reynolds, L. P., and Redmer, D. A. (1996). Effects of gonadotropin treatment and withdrawal on follicular growth, cell proliferation, and atresia in ewes. Biol. Reprod. 55, 693–702.
| Effects of gonadotropin treatment and withdrawal on follicular growth, cell proliferation, and atresia in ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XltlKgur8%3D&md5=a0b4d69a1714173d13739200ad4eccbeCAS | 8862789PubMed |
Jurisicova, A., Taniuchi, A., Li, H., Shang, Y., Antenos, M., Detmar, J., Xu, J., Matikainen, T., Benito Hernandez, A., Nunez, G., and Casper, R. F. (2007). Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri. J. Clin. Invest. 117, 3971–3978.
| 1:CAS:528:DC%2BD2sXhsValsLzI&md5=0debfa1617a3ba00557118fc14b71256CAS | 18037991PubMed |
Ke, F., Bouillet, P., Kaufmann, T., Strasser, A., Kerr, J., and Voss, A. K. (2013). Consequences of the combined loss of BOK and BAK or BOK and BAX. Cell Death Dis. 4, e650.
| Consequences of the combined loss of BOK and BAK or BOK and BAX.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtVykt7bK&md5=223bada3a2172cf13cd5048ac86228a6CAS | 23744350PubMed |
Kerr, J. B., Hutt, K. J., Michalak, E. M., Cook, M., Vandenberg, C. J., Liew, S. H., Bouillet, P., Mills, A., Scott, C. L., Findlay, J. K., and Strasser, A. (2012). DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa. Mol. Cell 48, 343–352.
| DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtl2kt7nJ&md5=99ea856b7351a88f91aea7f97f3fe776CAS | 23000175PubMed |
Kim, M. R., and Tilly, J. L. (2004). Current concepts in Bcl-2 family member regulation of female germ cell development and survival. Biochim. Biophys. Acta 1644, 205–210.
| Current concepts in Bcl-2 family member regulation of female germ cell development and survival.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhslWnsrs%3D&md5=4014ae6de439b709f152b9c291980caeCAS | 14996504PubMed |
Knudson, C. M., Tung, K. S., Tourtellotte, W. G., Brown, G. A., and Korsmeyer, S. J. (1995). Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270, 96–99.
| Bax-deficient mice with lymphoid hyperplasia and male germ cell death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXosFOmsb4%3D&md5=3916f236fbdcea20dd9979f468a81b95CAS | 7569956PubMed |
Liew, S. H., Vaithiyanathan, K., Cook, M., Bouillet, P., Scott, C. L., Kerr, J. B., Strasser, A., Findlay, J. K., and Hutt, K. J. (2014). Loss of the proapoptotic BH3-only protein BCL-2 modifying factor prolongs the fertile life span in female mice. Biol. Reprod. 90, 77.
| Loss of the proapoptotic BH3-only protein BCL-2 modifying factor prolongs the fertile life span in female mice.Crossref | GoogleScholarGoogle Scholar | 24571986PubMed |
Livera, G., Petre-Lazar, B., Guerquin, M. J., Trautmann, E., Coffigny, H., and Habert, R. (2008). p63 null mutation protects mouse oocytes from radio-induced apoptosis. Reproduction 135, 3–12.
| p63 null mutation protects mouse oocytes from radio-induced apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhs1CksL4%3D&md5=e4eda9687eb8089ffb89f2c5c5d65076CAS | 18159078PubMed |
Lobascio, A. M., Klinger, F. G., Scaldaferri, M. L., Farini, D., and De Felici, M. (2007). Analysis of programmed cell death in mouse fetal oocytes. Reproduction 134, 241–252.
| Analysis of programmed cell death in mouse fetal oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVKlsrfJ&md5=71c9b3f83361eac363398b897a9d6c41CAS | 17660234PubMed |
Matikainen, T., Perez, G. I., Zheng, T. S., Kluzak, T. R., Rueda, B. R., Flavell, R. A., and Tilly, J. L. (2001). Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology 142, 2468–2480.
| 1:CAS:528:DC%2BD3MXjvFGns70%3D&md5=c9e69039f473aafeec430565ab6b79b2CAS | 11356696PubMed |
McGee, E. A., Hsu, S. Y., Kaipia, A., and Hsueh, A. J. (1998). Cell death and survival during ovarian follicle development. Mol. Cell. Endocrinol. 140, 15–18.
| Cell death and survival during ovarian follicle development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXks1OgtLg%3D&md5=6b052176efb76ef3e3c4284bbb060c35CAS | 9722162PubMed |
Michalak, E. M., Jansen, E. S., Happo, L., Cragg, M. S., Tai, L., Smyth, G. K., Strasser, A., Adams, J. M., and Scott, C. L. (2009). Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ. 16, 684–696.
| Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXks1ygsLc%3D&md5=f2b43d3cc13e6de9b1298388bb11e7fcCAS | 19148184PubMed |
Morita, Y., and Tilly, J. L. (1999). Oocyte apoptosis: like sand through an hourglass. Dev. Biol. 213, 1–17.
| Oocyte apoptosis: like sand through an hourglass.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXlt1Wrsr0%3D&md5=0a78d7298a461bc520090553ef74cde4CAS | 10452843PubMed |
Morita, Y., Perez, G. I., Maravei, D. V., Tilly, K. I., and Tilly, J. L. (1999). Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro. Mol. Endocrinol. 13, 841–850.
| Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXjs1ynsr0%3D&md5=594ece51629b7e3cfe647e35211d1b3fCAS | 10379884PubMed |
Morita, Y., Maravei, D. V., Bergeron, L., Wang, S., Perez, G. I., Tsutsumi, O., Taketani, Y., Asano, M., Horai, R., Korsmeyer, S. J., Iwakura, Y., Yuan, J., and Tilly, J. L. (2001). Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function. Cell Death Differ. 8, 614–620.
| Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXltFarurk%3D&md5=0818075ac3e9379f6ea486c4042b8446CAS | 11536012PubMed |
Motoyama, N., Wang, F., Roth, K. A., Sawa, H., Nakayama, K., Negishi, I., Senju, S., Zhang, Q., Fujii, S., and Loh, D. Y. (1995). Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267, 1506–1510.
| Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXktlCltLk%3D&md5=59723558656cd974d3a724c49f6b721eCAS | 7878471PubMed |
Motta, P. M., Nottola, S. A., and Makabe, S. (1997). Natural history of the female germ cell from its origin to full maturation through prenatal ovarian development. Eur. J. Obstet. Gynecol. Reprod. Biol. 75, 5–10.
| Natural history of the female germ cell from its origin to full maturation through prenatal ovarian development.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c7gvVKjsg%3D%3D&md5=51a2f48d29f4393f1993a91c28852478CAS | 9447340PubMed |
Myers, M., Morgan, F. H., Liew, S. H., Zerafa, N., Gamage, T. U., Sarraj, M., Cook, M., Kapic, I., Sutherland, A., Scott, C. L., Strasser, A., Findlay, J. K., Kerr, J. B., and Hutt, K. J. (2014). PUMA regulates germ cell loss and primordial follicle endowment in mice. Reproduction 148, 211–219.
| PUMA regulates germ cell loss and primordial follicle endowment in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXht1GgurvO&md5=8246259d1a6b43d6d485ade5b9d1ca4fCAS | 24859845PubMed |
Pepling, M. E., and Spradling, A. C. (2001). Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev. Biol. 234, 339–351.
| Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktFKjur8%3D&md5=c0d5c8d8f74645291921b5f67454d03dCAS | 11397004PubMed |
Perez, G. I., Knudson, C. M., Leykin, L., Korsmeyer, S. J., and Tilly, J. L. (1997). Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction. Nat. Med. 3, 1228–1232.
| Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXntFantbg%3D&md5=68e38cadde8406b0e5b843d2b8ef3837CAS | 9359697PubMed |
Perez, G. I., Robles, R., Knudson, C. M., Flaws, J. A., Korsmeyer, S. J., and Tilly, J. L. (1999). Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat. Genet. 21, 200–203.
| Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXpsVCktw%3D%3D&md5=fb171b2599d02ff44451ab06c19bc76dCAS | 9988273PubMed |
Perez, G. I., Jurisicova, A., Wise, L., Lipina, T., Kanisek, M., Bechard, A., Takai, Y., Hunt, P., Roder, J., Grynpas, M., and Tilly, J. L. (2007). Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice. Proc. Natl Acad. Sci. USA 104, 5229–5234.
| Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjvFCguro%3D&md5=f094bb7f269451d7c1ab5c742458686fCAS | 17360389PubMed |
Pesce, M., and De Felici, M. (1994). Apoptosis in mouse primordial germ cells: a study by transmission and scanning electron microscope. Anat. Embryol. (Berl.) 189, 435–440.
| Apoptosis in mouse primordial germ cells: a study by transmission and scanning electron microscope.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2cznvFChtQ%3D%3D&md5=7da31ebc7ecbaff4eeafcc4bdf4f3217CAS | 8092494PubMed |
Pru, J. K., and Tilly, J. L. (2001). Programmed cell death in the ovary: insights and future prospects using genetic technologies. Mol. Endocrinol. 15, 845–853.
| Programmed cell death in the ovary: insights and future prospects using genetic technologies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjvFKjs7w%3D&md5=d6fc41ac87a5ae15ab3d9d3a0b37973bCAS | 11376105PubMed |
Ratts, V. S., Flaws, J. A., Kolp, R., Sorenson, C. M., and Tilly, J. L. (1995). Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology 136, 3665–3668.
| 1:CAS:528:DyaK2MXntFKntbc%3D&md5=0e421c3f6f66aa12162a64c65291f7e7CAS | 7628407PubMed |
Ried, H. L., and Jaffe, N. (1994). Radiation-induced changes in long-term survivors of childhood cancer after treatment with radiation therapy. Semin. Roentgenol. 29, 6–14.
| Radiation-induced changes in long-term survivors of childhood cancer after treatment with radiation therapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c7nsVehtQ%3D%3D&md5=c1783c91083006d6c4c479bd8bd36e73CAS | 7510420PubMed |
Riedlinger, G., Okagaki, R., Wagner, K. U., Rucker, E. B., Oka, T., Miyoshi, K., Flaws, J. A., and Hennighausen, L. (2002). Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary. Biol. Reprod. 66, 438–444.
| Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XotVSktw%3D%3D&md5=c1e3c84b1ea9ca1ae4d5b230e48a8592CAS | 11804960PubMed |
Rolaki, A., Drakakis, P., Millingos, S., Loutradis, D., and Makrigiannakis, A. (2005). Novel trends in follicular development, atresia and corpus luteum regression: a role for apoptosis. Reprod. Biomed. Online 11, 93–103.
| Novel trends in follicular development, atresia and corpus luteum regression: a role for apoptosis.Crossref | GoogleScholarGoogle Scholar | 16102296PubMed |
Rucker, E. B., Dierisseau, P., Wagner, K. U., Garrett, L., Wynshaw-Boris, A., Flaws, J. A., and Hennighausen, L. (2000). Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol. Endocrinol. 14, 1038–1052.
| Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXlt1WgurY%3D&md5=03c19dc3eecbbaf57ad47c967de031a5CAS | 10894153PubMed |
Sai, T., Goto, Y., Yoshioka, R., Maeda, A., Matsuda, F., Sugimoto, M., Wongpanit, K., Jin, H. Z., Li, J. Y., and Manabe, N. (2011). Bid and Bax are involved in granulosa cell apoptosis during follicular atresia in porcine ovaries. J. Reprod. Dev. 57, 421–427.
| Bid and Bax are involved in granulosa cell apoptosis during follicular atresia in porcine ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXpslOhs7w%3D&md5=74f862576a946a3b8eccba3136a4fe45CAS | 21441714PubMed |
Skaznik-Wikiel, M., Tilly, J. C., Lee, H. J., Niikura, Y., Kaneko-Tarui, T., Johnson, J., and Tilly, J. L. (2007). Serious doubts over ‘Eggs forever?’. Differentiation 75, 93–99.
| Serious doubts over ‘Eggs forever?’.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjsVSltbs%3D&md5=263c43e6888766bff85cabde6a8d4a1fCAS | 17316379PubMed |
Stallock, J., Molyneaux, K., Schaible, K., Knudson, C. M., and Wylie, C. (2003). The pro-apoptotic gene Bax is required for the death of ectopic primordial germ cells during their migration in the mouse embryo. Development 130, 6589–6597.
| The pro-apoptotic gene Bax is required for the death of ectopic primordial germ cells during their migration in the mouse embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXitlCiuw%3D%3D&md5=bacf261c12174e6d9372482df15e0fa7CAS | 14660547PubMed |
Strasser, A., Harris, A. W., Huang, D. C., Krammer, P. H., and Cory, S. (1995). Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 14, 6136–6147.
| 1:CAS:528:DyaK28XjtVKisg%3D%3D&md5=cf2e7b9d934b73137cb88ffe423ab61fCAS | 8557033PubMed |
Strasser, A., Cory, S., and Adams, J. M. (2011). Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 30, 3667–3683.
| Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVKit77M&md5=3efae18b6da3b9b651d41934e74a706dCAS | 21863020PubMed |
Suh, E. K., Yang, A., Kettenbach, A., Bamberger, C., Michaelis, A. H., Zhu, Z., Elvin, J. A., Bronson, R. T., Crum, C. P., and McKeon, F. (2006). p63 protects the female germ line during meiotic arrest. Nature 444, 624–628.
| p63 protects the female germ line during meiotic arrest.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1KjurnM&md5=8e55a73afac3cd8b29b1b56cf36af497CAS | 17122775PubMed |
Tilly, J. L. (2001). Commuting the death sentence: how oocytes strive to survive. Nat. Rev. Mol. Cell Biol. 2, 838–848.
| Commuting the death sentence: how oocytes strive to survive.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXotlartLk%3D&md5=632ab0c8abc2f6e0984590be7a546657CAS | 11715050PubMed |
Tingen, C., Kim, A., and Woodruff, T. K. (2009). The primordial pool of follicles and nest breakdown in mammalian ovaries. Mol. Hum. Reprod. 15, 795–803.
| The primordial pool of follicles and nest breakdown in mammalian ovaries.Crossref | GoogleScholarGoogle Scholar | 19710243PubMed |
Vaskivuo, T. E., Anttonen, M., Herva, R., Billig, H., Dorland, M., te Velde, E. R., Stenback, F., Heikinheimo, M., and Tapanainen, J. S. (2001). Survival of human ovarian follicles from fetal to adult life: apoptosis, apoptosis-related proteins, and transcription factor GATA-4. J. Clin. Endocrinol. Metab. 86, 3421–3429.
| 1:CAS:528:DC%2BD3MXlt1Gju78%3D&md5=f04d53a637d5d8f23bd19e662921137cCAS | 11443219PubMed |
Watanabe, M., Shirayoshi, Y., Koshimizu, U., Hashimoto, S., Yonehara, S., Eguchi, Y., Tsujimoto, Y., and Nakatsuji, N. (1997). Gene transfection of mouse primordial germ cells in vitro and analysis of their survival and growth control. Exp. Cell Res. 230, 76–83.
| Gene transfection of mouse primordial germ cells in vitro and analysis of their survival and growth control.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkvF2jtQ%3D%3D&md5=adbf9b16598e85ddcf139231376c806fCAS | 9013709PubMed |
Waxman, J. (1983). Chemotherapy and the adult gonad: a review. J. R. Soc. Med. 76, 144–148.
| 1:STN:280:DyaL3s7jvVKhsw%3D%3D&md5=ea22570d68b2d1e170b5e27f167ed89fCAS | 6338232PubMed |
Yang, A., Kaghad, M., Wang, Y., Gillett, E., Fleming, M. D., Dotsch, V., Andrews, N. C., Caput, D., and McKeon, F. (1998). p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol. Cell 2, 305–316.
| p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmsVyqt7c%3D&md5=cb9172fd9d730d3216db7c15e7601392CAS | 9774969PubMed |
Youle, R. J., and Strasser, A. (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9, 47–59.
| The BCL-2 protein family: opposing activities that mediate cell death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVKrsrrP&md5=8a54314ed20481654dfa0794babc72cdCAS | 18097445PubMed |
Yuan, W., and Giudice, L. C. (1997). Programmed cell death in human ovary is a function of follicle and corpus luteum status. J. Clin. Endocrinol. Metab. 82, 3148–3155.
| 1:CAS:528:DyaK2sXlvFemurw%3D&md5=9f294448751508b26d372900da3acd54CAS | 9284760PubMed |
Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997). Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90, 405–413.
| Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlsVKrsrk%3D&md5=b7068cec357c5d8abfca35a7c769d27cCAS | 9267021PubMed |
