Premature ovarian failure (POF) is defined as cessation of menstruation and associated elevation of gonadotropin levels (FSH >40 IU/l) as a result of decreased ovarian function prior to the age of 40. An estimated 1% of the population is affected before age 40, with 0.1% affected prior to age 30. Although the causes for POF are many, the majority of POF cases have idiopathic etiologies. In an effort to investigate potential mechanisms of the disease, genetic determinants of POF have received particular attention in recent years. Transgenic mouse models have been instrumental in the discovery of novel genetic determinants of gonadal development and failure and have informed research identifying mutations in women with POF. Here, we review recent developments in identifying genetic determinants of POF.

1.
Ackert CL, Gittens JE, O’brien MJ, Eppig JJ, Kidder GM: Intercellular communication via Connexin43 gap junctions is required for ovarian folliculogenesis in the mouse. Dev Biol 233:258–270 (2001).
2.
Agoulnik LY, Cho Y, Niederberger C, Kieback DG, Cooney AJ: Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF. FEBS Lett 424:73–78 (1998).
3.
Aittomäki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, et al: Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82:959–968 (1995).
4.
Allen EG, Sullivan AK, Marcus M, Small C, Dominguez C, et al: Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod 22:2142–2152 (2007).
5.
Allen LA, Achermann JC, Pakarinen P, Kotlar TJ, Huhtaniemi IT, et al: A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotropic hypogonadism: clinical and molecular characteristics. Hum Reprod 18:251–256 (2003).
6.
Anasti JN: Premature ovarian failure: an update. Fertil Steril 70:1–15 (1998).
7.
Anasti JN, Kalantaridou SN, Kimzey LM, Defensor RA, Nelson LM: Bone loss in young women with karyotypically normal spontaneous premature ovarian failure. Obstet Gynecol 91:12–15 (1998).
8.
Anderson RA, Fulton N, Cowan G, Coutts S, Saunders PT: Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis. BMC Dev Biol 18:136 (2007).
9.
Anttonen M, Ketola I, Parviainen H, Pusa AK, Heikinheimo M: FOG-2 and GATA-4 are coexpressed in the mouse ovary and can modulate mullerian-inhibiting substance expression. Biol Reprod 68:1333–1340 (2003).
10.
Bayne RA, Martins da Silva SJ, Anderson RA: Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Mol Hum Reprod 10:373–381 (2004).
11.
Beau I, Touraine P, Meduri G, Gougeon A, Desroches A, et al: A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest 102:1352–1359 (1998).
12.
Bione S, Rizzolio F, Sala C, Ricotti R, Goegan M, et al: Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B. Hum Reprod 19:2759–2766 (2004).
13.
Bodega B, Porta C, Crosignani PG, Ginelli E, Marozzi A: Mutations in the coding region of the FOXL2 gene are not a major cause of idiopathic premature ovarian failure. Mol Hum Reprod 10:555–557 (2004).
14.
Bodega B, Bione S, Dalpra L, Toniolo D, Ornaghi F, et al: Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation. Hum Reprod 21:952–957 (2006).
15.
Braw-Tal R, McNatty KP, Smith P, Heath DA, Hudson NL, et al: Ovaries of ewes homozygous for the X-linked Inverdale gene (FecXI) are devoid of secondary and tertiary follicles but contain many abnormal structures. Biol Reprod 49:895–907 (1993).
16.
Bretherick KL, Fluker MR, Robinson WP: FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure. Hum Genet 117:376–382 (2005).
17.
Bullejos M, Koopman P: Germ cells enter meiosis in a rostrocaudal wave during development of the mouse ovary. Mol Reprod Dev 68:422–428 (2004).
18.
Cantley LC: The phosphoinositide 3-kinase pathway. Science 296:1655–1657 (2002).
19.
Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF: Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol 204:373–384 (1998).
20.
Castrillon DH, Quade BJ, Wang TY, Quigley C, Crum CP: The human VASA gene is specifically expressed in the germ cell lineage. Proc Natl Acad Sci USA 97:9585–9590 (2000).
21.
Castrillon DH, Miao L, Kollipara R, Homer JW, DePinho RA: Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 301:215–218 (2003).
22.
Chatterjee S, Modi D, Maitra A, Kadam S, Patel Z, et al: Screening for FOXL2 gene mutations in women with premature ovarian failure: an Indian experience. Reprod Biomed Online 15:554–560 (2007).
23.
Chen F, Cooney AJ, Wang Y, Law SW, O’Malley BW: Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol 8:1434–1444 (1994).
24.
Choi Y, Rajkovic A: Genetics of early mammalian folliculogenesis. Cell Mol Life Sci 63:579–590 (2006a).
25.
Choi Y, Rajkovic A: Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters. J Biol Chem 281:35747–35756 (2006b).
26.
Conway GS, Payne NN, Webb J, Murray A, Jacobs PA: Fragile X premutation screening in women with premature ovarian failure. Hum Reprod 13:1184–1187 (1998).
27.
Cooke HJ, Lee M, Kerr S, Ruggiu M: A murine homologue of the human DAZ gene is autosomal and expressed only in male and female gonads. Hum Mol Genet 5:513–516 (1996).
28.
Coulam CB, Adamson SC, Annegers JF: Incidence of premature ovarian failure. Obstet Gynecol 67:604–606 (1986).
29.
Cremers FP, van de Pol DJ, Diergaarde PJ, Wieringa B, Nussbaum RL, et al: Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. Genomics 4:41–46 (1989).
30.
Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, et al: The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 27:159–166 (2001).
31.
Cutler WB, Genovese-Stone E: Wellness in women after 40 years of age: the role of sex hormones and pheromones. Dis Mon 44:421–546 (1998).
32.
De Baere E, Lemercier B, Christin-Maitre S, Durval D, Messiaen L, et al: FOXL2 mutation screening in a large panel of POF patients and XX males. J Med Genet 39:e43 (2002).
33.
Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP: Pten is essential for embryonic development and tumour suppression. Nat Genet 19:348–355(1998).
34.
Di Pasquale E, Beck-Peccoz P, Persani L: Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 75:106–111 (2004).
35.
Di Pasquale E, Rossetti R, Marozzi A, Bodega B, Borgato S, et al: Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab 91:1976–1979 (2006).
36.
Diaz FJ, Wigglesworth K, Eppig JJ: The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion. Dev Biol 299:91–104 (2006).
37.
Diaz FJ, Wigglesworth K, Eppig JJ: Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci 120:1330–1340 (2007a).
38.
Diaz FJ, Wigglesworth K, Eppig JJ: Oocytes are required for the preantral granulosa cell to cumulus cell transition in mice. Dev Biol 305:300–311 (2007b).
39.
Dierich A, Ram Sairam M, Monaco L, Maria Fimia G, Gansmuller A, et al: Impairing follicle stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci USA 95:13612–13617 (1998).
40.
Dixit H, Rao LK, Padmalatha V, Kanakavalli M, Deenadayal M, et al: Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure. Menopause 12:749–754 (2005).
41.
Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, et al: Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet 119:408–415 (2006).
42.
Doherty E, Pakarinen P, Tiitinen A, Kiilavuori A, Huhtaniemi I, et al: A novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. J Clin Endocrinol Metab 87:1151–1155 (2002).
43.
Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM: Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531–535 (1996).
44.
Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matsuk MM: The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 12:1809–1817 (1998).
45.
Ebralidze A, Wang Y, Petkova V, Ebralidse K, Junghans RP: RNA leaching of transcription factors disrupts transcription in myotonic dystrophy. Science 303:383–387 (2004).
46.
Elvin JA, Yan C, Wang P, Nishimori K, Matzuk MM: Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Mol Endocrinol 13:1018–1034 (1999).
47.
Elvin JA, Yan C, Matzuk MM: Oocyte-expressed TGF-beta superfamily members in female fertility. Mol Cell Endocrinol 159:1–5 (2000).
48.
Epifano O, Liang LF, Famiari M, Moos MC, Dean J: Coordinate expression of the three zona pellucida genes during mouse oogenesis. Development 121:1947–1956 (1995).
49.
Eppig J: Mouse oocytes control metabolic co-operativity between oocytes and cumulus cells. Reprod Fertil Dev 17:1–2 (2005).
50.
Falender AE, Shimada M, Lo YK, Richards JS: TAF4b, a TBP associated factor, is required for oocyte development and function. Dev Biol 288:405–419 (2005).
51.
Fero ML, Rivkin M, Tasch M, Porter R, Carow CE, et al: A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27kip1 deficient mice. Cell 85:733–744 (1996).
52.
Freiman RN, Albright SR, Zheng S, Sha WC, Hammer RE, Tjian R: Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science 293:2084–2087 (2001).
53.
Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, et al: Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047–1058 (1991).
54.
Fujiwara Y, Komiya T, Kawabata H, Sato M, Fujimoto H, et al: Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell linage. Proc Natl Acad Sci USA 91:12258–12262 (1994).
55.
Galloway SM, McNatty KP, Cambridge LM, Gaitinen MP, Juengel JL, et al: Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 25:279–283 (2000).
56.
Gillio-Meina C, Hui YY, LaVoie HA: GATA-4 and GATA-6 transcription factors: expression, immunohistochemical localization, and possible function in the porcine ovary. Biol Reprod 68:412–422 (2003).
57.
Gittens JE, Mhawi AA, Lidington D, Ouellette Y, Kidder GM: Functional analysis of gap junctions in ovarian granulose cells: distinct role for connexin43 in early stages of folliculogenesis. Am J Physiol Cell Physiol 284:C880–C887 (2003).
58.
Gosden RG: Gonadal tissue cryopreservation and transplantation. Reprod Biomed Online 1:64–67 (2002).
59.
Gosden RG: Prospects for oocyte banking and in vitro maturation. J Natl Cancer Inst Monogr 34:60–63 (2005).
60.
Gosden RG, Faddy MJ: Biological bases of premature ovarian failure. Reprod Fertil Dev 10:73–78 (1998).
61.
Goswami D, Conway GS: Premature ovarian failure. Hum Reprod Update 11:391–410 (2005).
62.
Gromoll J, Simoni M, Nordhoff V, Behre HM, De Geyter C, Nieschlag E: Functional and clinical consequences of mutations in the FSH receptor. Mol Cell Endocrinol 125:177–182 (1996).
63.
Hagerman PJ, Hagerman RJ: The fragile-X premutation: a maturing perspective. Am J Hum Genet 74:805–816 (2004).
64.
Harris SE, Chand AL, Winship IM, Gersak K, Aittomäki K, Shelling AN: Identification of novel mutations in FOXL2 associated with premature ovarian failure. Mol Hum Reprod 8:729–733 (2002).
65.
Heikinheimo M, Ermolaeva M, Bielinska M, Rahman NA, Narita N, et al: Expression and hormonal regulation of transcription factors GATA-4 and GATA-6 in the mouse ovary. Endocrinology 138:3505–3514 (1997).
66.
Hundscheid RD, Sistermans EA, Thomas CM, Braat DD, Straatman H, et al: Imprinting effect in premature ovarian failure confined to paternally inherited fragile X premutations. Am J Hum Genet 66:413–418 (2000).
67.
Huntriss J, Gosden R, Hinkins M, Oliver B, Miller D, et al: Isolation, characterization and expression of the human factor in the germline alpha (FIGLA) gene in ovarian follicles and oocytes. Mol Hum Reprod 8:1087–1095 (2002).
68.
Huntriss J, Hinkins M, Picton HM: cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles. Mol Hum Reprod 12:283–289 (2006).
69.
Jacobsen BK, Heuch I, Kvale G: Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol 157:923–929 (2003).
70.
Joshi S, Davies H, Sims LP, Levy SE, Dean J: Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor. BMC Dev Biol 13:67 (2007).
71.
Kalantaridou SN, Naka KK, Bechlioulis A, Makrigiannakis A, Michalis L, Chrousos GP: Premature ovarian failure, endothelial dysfunction and estrogen-progestogen replacement. Trends Endocrinol Metab 17:101–109 (2006).
72.
Kaldis P: Another piece of the p27kip1 puzzle. Cell 128:241–244 (2007).
73.
Katz D, Niederberger C, Slaughter GR, Cooney AJ: Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor. Endocrinology 138:4364–4372 (1997).
74.
Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, et al: Oct4 is required for primordial germ cell survival. EMBO Rep 5:1078–1083 (2004).
75.
Kerr CL, Hill CM, Blumenthal PD, Gearhart JD: Expression of pluripotent stem cell markers in the human fetal ovary. Hum Reprod 23:589–599 (2008).
76.
Kidder GM, Mhawi AA: Gap junctions and ovarian folliculogenesis. Reproduction 123:613–620 (2002).
77.
Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Offman ES, et al: Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27kip1. Cell 85:721–732 (1996).
78.
Kovanci E, Rohozinski J, Simpson JL, Heard MJ, Bishop CE, Carson SA: Growth differentiating factor-9 mutations may be associated with premature ovarian failure. Fertil Steril 87:143–146 (2007a).
79.
Kovanci E, Simpson JL, Amato P, Rohozinski J, Heard MJ, et al: Oocyte-specific G-protein-coupled receptor 3 (GPR3): no perturbations found in 82 women with premature ovarian failure (first report). Fertil Steril 90 (2007b).
80.
Krauss CM, Turksoy RN, Atkins L, McLaughlin C, Brown LG, Page DC: Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome. N Engl J Med 317:125–131 (1987).
81.
Kumar TR, Wang Y, Lu N, Matzuk MM: Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15:201–204 (1997).
82.
Kurosaka S, Eckardt S, McLaughlin KJ: Pluripotent lineage definition in bovine embryos by Oct4 transcript localization. Biol Reprod 71:1578–1582 (2004).
83.
Kwintkiewicz J, Cai Z, Stocco C: Follicle-stimulating hormone-induced activation of Gata4 contributes in the up-regulation of Cyp19 expression in rat granulosa cells. Mol Endocrinol 21:933–947 (2007).
84.
Lachlan KL, Youings S, Costa T, Jacobs PA, Thomas NS: A clinical and molecular study of 26 females with Xp deletions with special emphasis on inherited deletions. Hum Genet 118:640–651 (2006).
85.
Lacombe A, Lee H, Zahed L, Choucair M, Muller J, et al: Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. Am J Hum Genet 79:113–119 (2006).
86.
Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, et al: Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol 154:739–744 (2006).
87.
Laitinen MP, Anttonen M, Ketola I, Wilson DB, Ritvos O, et al: Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors. J Clin Endocrinol Metab 85:3476–3483 (2000).
88.
Laml T, Schulz-Lobmeyr I, Obruca A, Huber JC, Hartmann BW: Premature ovarian failure: etiology and prospects. Gynecol Endocrinol 14:292–302 (2000).
89.
Lan ZJ, Gu P, Xu X, Cooney AJ: Expression of the orphan nuclear receptor, germ cell nuclear factor, in mouse gonads and preimplantation embryos. Biol Reprod 68:282–289 (2003a).
90.
Lan ZJ, Gu P, Xu X, Jackson KJ, DeMayo FJ, et al: GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility. EMBO J 22:4070–4081 (2003b).
91.
Lan ZJ, Xu X, Cooney AJ: Differential oocyte-specific expression of Cre recombinase activity in GDF-9ICre, Zp3cre, and Msx2Cre transgenic mice. Biol Reprod 71:1469–1474 (2004).
92.
Lasko PF, Ashburner M: The product of the Drosophila gene vasa is very similar to eukaryotic initiation factor-4A. Nature 335:611–617 (1988).
93.
Lavoie HA, McCoy GL, Blake CA: Expression of the GATA-4 and GATA-6 transcription factors in the fetal rat gonad and in the ovary during postnatal development and pregnancy. Mol Cell Endocrinol 227:31–40 (2004).
94.
Ledent C, Demeestere I, Blum D, Petermans J, Hämäläinen T, et al: Premature ovarian aging in mice deficient for Gpr3. Proc Natl Acad Sci USA 102:8922–8926 (2005).
95.
Ledig S, Röpke A, Haeusler G, Hinney B, Wieacker P: BMP15 mutations in XX gonadal dysgenesis and premature ovarian failure. Am J Obstet Gynecol 198:84.e1–5 (2008).
96.
Li S, Lu MM, Zhou D, Hammes SR, Morrisey EE: GLP-1: a novel zinc finger protein required in somatic cells of the gonad for germ cell development. Dev Biol 301:106–116 (2007).
97.
Liang L, Soyal SM, Dean J: FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Development 124:4939–4947 (1997).
98.
Liao WX, Moore RK, Otsuka F, Shimasaki S: Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep. J Biol Chem278:3713–3719 (2003).
99.
Liao WX, Moore RK, Shimasaki S: Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9. J Biol Chem 279:17391–17396 (2004).
100.
Lin Y, Page DC: Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice. Dev Biol 288:309–316 (2005).
101.
Liu K, Rajareddy S, Liu L, Jagarlamudi K, Boman K, et al: Control of mammalian oocyte growth and early follicular development by the oocyte P13 kinase pathway: new roles for an old timer. Dev Biol 299:1–11 (2006).
102.
Liu L, Rajareddy S, Reddy P, Du C, Jagarlamudi K, et al: Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a. Development 134:199–209 (2007).
103.
Loffler KA, Zarkower D, Koopman P: Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian development. Endocrinology 144:3237–3243 (2003).
104.
Maraschio P, Tupler R, Barbierato L, Dainotti E, Larizza D, et al: An analysis of Xq deletions. Hum Genet 97:375–381 (1996).
105.
Marozzi A, Manfredini E, Tibiletti MG, Furlan D, Villa N, et al: Molecular definition of Xq common-deleted region in patients affected by premature ovarian failure. Hum Genet 107:304–311 (2000).
106.
Matzuk MM, Lamb DJ: Genetic dissection of mammalian fertility pathways. Nat Cell Biol 4 Suppl:s41–s49 (2002).
107.
McCoard SA, Wise TH, Fahrenkrug SC, Ford JJ: Temporal and spatial localization patterns of Gata4 during porcine gonadogenesis. Biol Reprod 65:366–374 (2001).
108.
McCoard SA, Wise TH, Ford JJ: Expression levels of Mullerian-inhibiting substance, GATA4 and 17alpha-hydroxylase/17,20-lyase cytochrome P450 during embryonic gonadal development in two diverse breeds of swine. J Endocrinol 175:365–374 (2002).
109.
McGrath SA, Esquela AF, Lee SJ: Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9:131–136 (1995).
110.
McNatty KP, Smith P, Moore LG, Reader K, Lun S, et al: Oocyte-expressed genes affecting ovulation rate. Mol Cell Endocrinol 234:57–66 (2005).
111.
McNeilly JR, Saunders PT, Taggart M, Cranfield M, Cooke HJ, McNeilly AS: Loss of oocytes in Dazl knockout mice results in maintained ovarian steroidogenic function but altered gonadotropin secretion in adult animals. Endocrinology 141:4284–4294 (2000).
112.
Meduri G, Touraine P, Beau I, Lahuna O, Desroches A, et al: Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. J Clin Endocrinol Metab 88:3491–3498 (2003).
113.
Mehlmann LM: Oocyte-specific expression of Gpr3 is required for the maintenance of meiotic arrest in mouse oocytes. Dev Biol 288:397–404 (2005a).
114.
Mehlmann LM: Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction 130:791–799 (2005b).
115.
Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, et al: The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science 306:1947–1950 (2004).
116.
Moore RK, Shimasaki S: Molecular biology and physiological role of the oocyte factor, BMP-15. Mol Cell Endocrinol 234:67–73 (2005).
117.
Moore RK, Erickson GF, Shimasaki S: Are BMP-15 and GDF-9 primary determinants of ovulation quota in mammals? Trends Endocrinol Metab 15:356–361 (2004).
118.
Murray A: Premature ovarian failure and the FMR1 gene. Semin Reprod Med 18:59–66 (2000).
119.
Murray A, Ennis S, MacSwiney F, Webb J, Morton NE: Reproductive and menstrual history of females with fragile X expansions. Eur J Hum Genet 8:247–252 (2000).
120.
Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, et al: Mice lacking p27kip1 display increased body size, multiple organ hyperplasia rentinal dysplasia, and pituitary tumors. Cell 85:707–720 (1996).
121.
Oberle I, Rousseau F, Heitz D, Kretz C, Devys D, et al: Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252:1097–1102 (1991).
122.
Ogata T, Matsuo N: Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. Hum Genet 95:607–629 (1995).
123.
Ogata T, Muroya K, Matsuo N, Shinohara O, Yorifuji T, et al: Turner syndrome and Xp deletions: clinical and molecular studies in 47 patients. J Clin Endocrinol Metab 86:5498–5508 (2001).
124.
Ongeri EM, Verderame MF, Hammond JM: The TATA binding protein associated factor 4b (TAF4b) mediates FSH stimulation of the IGFBP-3 promoter in cultured porcine ovarian granulosa cells. Mol Cell Endocrinol 278:29–35 (2007).
125.
Otsuka F, Yao Z, Lee T, Yamamoto S, Erickson GF, Shimasaki S: Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem 275:39523–39528 (2000).
126.
Otsuka F, Yamamoto S, Erickson GF, Shimasaki S: Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. J Biol Chem 276:11387–11392 (2001).
127.
Ottolenghi C, Omari S, Garcia-Ortiz JE, Uda M, Crisponi L, et al: Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet 14:2053–2062 (2005).
128.
Ottolenghi C, Pelosi E, Tran J, Colombino M, Douglass E, et al: Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells. Hum Mol Genet 16:2795–2804 (2007).
129.
Pal L, Santoro N: Premature ovarian failure (POF): discordance between somatic and reproductive aging. Ageing Res Rev 1:413–423 (2002).
130.
Pangas SA, Rajkovic A: Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update 12:65–76 (2006).
131.
Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, et al: Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci USA 103:8090–8095 (2006).
132.
Pennetier S, Uzbekova S, Perreau C, Papillier P, Mermillod P, Dalbiès-Tran R: Spatio-temporal expression of the germ cell marker genes MATER, ZAR1, GDF9, BMP15, and VASA in adult bovine tissues, oocytes, and preimplantation embryos. Biol Reprod 71:1359–1366 (2004).
133.
Perez GI, Jurisicova A, Wise L, Lipina T, Kanisek M, et al: 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 (2007).
134.
Pesce M, Schöler HR: Oct-4: control of totipotency and germline determination. Mol Reprod Dev 55:452–457 (2000).
135.
Pesce M, Gross MK, Schöler HR: In line with our ancestors: Oct-4 and the mammalian germ. Bioessays 20:722–732 (1998).
136.
Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, et al: Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci USA 96:1563–1568 (1999).
137.
Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A: NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet 81:576–581 (2007).
138.
Qin Y, Zhao H, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A: Analysis of LHX8 mutation in premature ovarian failure. Fertil Steril 89:1012–1014 (2008).
139.
Rajareddy S, Reddy P, Du C, Liu L, Jagarlamudi K, et al: p27kip1 (cyclin-dependent kinase inhibitor 1B) controls ovarian development by suppressing follicle endowment and activation and promoting follicle atresia in mice. Mol Endocrinol 21:2189–2202 (2007).
140.
Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM: NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 305:1157–1159 (2004).
141.
Reddy P, Shen L, Ren C, Boman K, Lundin E, et al: Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Dev Biol 281:160–170 (2005).
142.
Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, et al: Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 319:611–613 (2008).
143.
Rizzolio F, Bione S, Sala C, Goegan M, Gentile M, et al: Chromosomal rearrangements in Xq and premature ovarian failure: mapping of 25 new cases and review of the literature. Hum Reprod 21:1477–1483 (2006).
144.
Rizzolio F, Bione S, Villa A, Berti E, Cassetti A, et al: Spatial and temporal expression of POF1B, a gene expressed in epithelia. Gene Expr Patterns 7:529–534 (2007).
145.
Rosetti F, Rizzolio F, Pramparo T, Sala C, Bione S, et al: A susceptibility gene for premature ovarian failure (POF) maps to proximal Xq28. Eur J Hum Genet 12:829–834 (2004).
146.
Ruggiu M, Speed R, Taggart M, McKay SJ, Kilanowski F, et al: The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389:73–77 (1997).
147.
Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, et al: The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 131:933–942 (2004).
148.
Schwartz C, Fitch N, Phelan MC, Richer CL, Stevenson R: Two sisters with a distal deletion at the Xq26/Xq27 interface: DNA studies indicate that the gene locus for factor IX is present. Hum Genet 76:54–57 (1987).
149.
Seligman J, Page DC: The Dazh gene is expressed in male and female embryonic gonads before germ cell sex differentiation. Biochem Biophys Res Commun 245:878–882 (1998).
150.
Senöz S, Direm B, Gülekli B, Gökmen O: Estrogen deprivation, rather than age, is responsible for the poor lipid profile and carbohydrate metabolism in women. Maturitas 25:107–114 (1996).
151.
Silverman E, Eimerl S, Orly J: CCAAT enhancer-binding protein beta and GATA-4 binding regions within the promoter of the steroidogenic acute regulatory protein (StAR) gene are required for transcription in rat ovarian cells. J Biol Chem 274:17987–17996 (1999).
152.
Silverman E, Yivgi-Ohana N, Sher N, Bell M, Eimerl S, Orly J: Transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene: GATA-4 and CCAAT/enhancer-binding protein beta confer synergistic responsiveness in hormone-treated rat granulosa and HEK293 cell models. Mol Cell Endocrinol 252:92–101 (2006).
153.
Simon AM, Goodenough DA, Li E, Paul DL: Female infertility in mice lacking connexin 37. Nature 385:525–529 (1997).
154.
Simpson JL, Rajkovic A: Ovarian differentiation and gonadal failure. Semin Med Genet 89:186–200 (1999).
155.
Smith P, O WS, Corrigan KA, Smith T, Lundy T, et al: Ovarian morphology and endocrine characteristics of female sheep fetuses that are heterozygous or homozygous for the inverdale prolificacy gene (fecX1). Biol Reprod 57:1183–1192 (1997).
156.
Snieder H, MacGregor AJ, Spector TD: Genes control the cessation of a woman’s reproductive life: a twin study of hysterectomy and age at menopause. J Clin Endocrinol Metab 83:1875–1880 (1998).
157.
Song JL, Wessel GM: How to make an egg: transcriptional regulation in oocytes. Differentiation 73:1–17 (2005).
158.
Soyal SM, Amleh A, Dean J: FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. Development 127:4645–4654 (2000).
159.
Speroff L, Fritz MA (eds): Amenorrhea, in Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp 401–464 (Lippincott Williams and Wilkins, Philadelphia 2005).
160.
Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, et al: Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39 (1998).
161.
Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, Looijenga LH: Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Hum Reprod 20:1466–1476 (2005).
162.
Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, et al: Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 20:402–412 (2005).
163.
Sundblad V, Chiauzzi VA, Escobar ME, Dain L, Charreau EH: Screening of FSH receptor gene in Argentine women with premature ovarian failure (POF). Mol Cell Endocrinol 222:53–59 (2004).
164.
Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, et al: High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol8:1169–1178 (1998).
165.
Suzumori N, Yan C, Matzuk MM, Rajkovic A: Nobox is a homeobox-encoding gene preferentially expressed in primordial and growing oocytes. Mech Dev 111:137–141 (2002).
166.
Suzumori N, Pangas SA, Rajkovic A: Candidate genes for premature ovarian failure. Curr Med Chem 14:353–357 (2007).
167.
Takakura K, Takebayashi K, Wang H, Kimura F, Kasahara K, Noda Y: Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome. Fertil Steril 75:207–209 (2001).
168.
Tanaka SS, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, et al: The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes Dev 14:841–853 (2000).
169.
Thomas FH, Ethier JF, Shimasaki S, Vanderhyden BC: Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors. Endocrinology 146:941–949 (2005).
170.
Toniolo D, Rizzolio F: X chromosome and ovarian failure. Semin Reprod Med 25:264–271 (2007).
171.
Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, et al: New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol 13:1844–1854 (1999).
172.
Tremblay JJ, Viger RS: GATA factors differentially activate multiple gonadal promoters through conserved GATA regulatory elements. Endocrinology 142:977–986 (2001).
173.
Trunca C, Therman E, Rosenwaks Z: The phenotypic effects of small, distal Xq deletions. Hum Genet 68:87–89 (1984).
174.
Tung JY, Rosen MP, Nelson LM, Turek PJ, Witte JS, et al: Variants in Deleted in Azoospermia-Like (DAZL) are correlated with reproductive parameters in men and women. Hum Genet 118:730–740 (2006).
175.
Uda M, Ottolenghi C, Crisponi L, Garcia JE, Deiana M, et al: Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum Mol Genet 13:1171–1181 (2004).
176.
Udar N, Yellore V, Chalukya M, Yelchits S, Silva-Garcia R, et al: Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients. Hum Mutat 22:222–228 (2003).
177.
Uygur D, Sengul O, Bayar D, Erdinc S, Batioglu S, Mollamahmutoglu L: Bone loss in young women with premature ovarian failure. Arch Gynecol Obstet 273:17–19 (2005).
178.
Uzielli ML, Guarducci S, Lapi E, Cecconi A, Ricci U, et al: Premature ovarian failure (POF) and fragile X premutation females: from POF to fragile X carrier identification, from fragile X carrier diagnosis to POF association data. Am J Med Genet 84:300–303 (1999).
179.
van Asselt KM, Kok HS, Pearson PL, Dubas JS, Peeters PH, et al: Heritability of menopausal age in mothers and daughters. Fertil Steril 82:1348–1351 (2004).
180.
van der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD: Age at menopause as a risk factor for cardiovascular mortality. Lancet 347:714–718 (1996).
181.
Vaskivuo TE, Anttonen M, Herva R, Billig H, Dorland M, et al: 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 (2001).
182.
Vaskivuo TE, Aittomäki K, Anttonen M, Ruokonen A, Herva R, et al: Effects of follicle-stimulating hormone (FSH) and human chorionic gonadotropin in individuals with an inactivating mutation of the FSH receptor. Fertil Steril 78:108–113 (2002).
183.
Vegetti W, Grazia Tibiletti M, Testa G, de Lauretis Y, Alagna F, et al: Inheritance in idiopathic premature ovarian failure: analysis of 71 cases. Hum Reprod 13:1796–1800 (1998).
184.
Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, et al: Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914 (1991).
185.
Vinci G, Christin-Maitre S, Pasquier M, Bouchard P, Fellous M, Veitia RA: FOXO3a variants in patients with premature ovarian failure. Clin Endocrinol (Oxf) 68:491–497 (2008).
186.
Voronina E, Lovasco LA, Gyuris A, Baumgartner RA, Parlow AF, Freiman RN: Ovarian granulosa cell survival and proliferation requires the gonad-selective TFIID subunit TAF4b. Dev Biol 303:715–726 (2007).
187.
Wang D, Kobayashi T, Zhou L, Nagahama Y: Molecular cloning and gene expression of Foxl2 in the Nile tilapia, Oreochromis niloticus. Biochem Biophys Res Commun 320:83–89 (2004).
188.
Woad KJ, Watkins WJ, Prendergast D, Shelling AN: The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol 46:242–244 (2006).
189.
Wu Y, Lu Y, Hu Y, Li R: Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human ovarian granulosa cell line. J Cell Biochem 96:751–759 (2005).
190.
Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, et al: Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15:854–866 (2001).
191.
Zerbetto I, Gromoll J, Luisi S, Reis FM, Nieschlag E, et al: Follicle-stimulating hormone receptor and DAZL gene polymorphisms do not affect the age of menopause. Fertil Steril [Epub ahead of print] (2008).
192.
Zhang P, Kerkela E, Skottman H, Levkov L, Kivinen K, et al: Distinct sets of developmentally regulated genes that are expressed by human oocytes and human embryonic stem cells. Fertil Steril 87:677–690 (2007).
193.
Zhang YL, Akmal KM, Tsuruta JK, Shang Q, Hirose T, et al: Expression of germ cell nuclear factor (GCNF/RTR) during spermatogenesis. Mol Reprod Dev 50:93–102 (1998).
194.
Zhao H, Qin Y, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A: Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure. Fertil Steril 88:1474–1476 (2007).
195.
Zhao H, Chen Z, Qin Y, Shi Y, Wang S, et al: Transcription factor FIGLA is mutated in patients with premature ovarian failure. Am J Hum Genet 82:1342–1348 (2008).
196.
Zhao XX, Suzumori N, Yamaguchi M, Suzumori K: Mutational analysis of the homeobox region of the human NOBOX gene in Japanese women who exhibit premature ovarian failure. Fertil Steril 83:1843–1844 (2005).
197.
Zheng P, Dean J: Oocyte-specific genes affect folliculogenesis, fertilization, and early development. Semin Reprod Med 25:243–251 (2007).
198.
Zinn AR, Ross JL: Turner syndrome and haploinsufficiency. Curr Opin Genet Dev 8:322–327 (1998).
199.
Zinn AR, Tonk VS, Chen Z, Flejter WL, Gardner HA, et al: Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1. Am J Hum Genet 63:1757–1766 (1998).
200.
Zwaka TP, Thomson JA: A germ cell origin of embryonic stem cells? Development 132:227–233 (2005).
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