PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: An update

Journal of Molecular Endocrinology

Volumn 53, Issue 3, 2014, Pages R103-R118

  Makker, Annu ^a   Goel, Madhu Mati ^a   Mahdi, Abbas Ali ^a  

^a KING GEORGE'S MEDICAL UNIVERSITY   (India)

Author keywords

Folliculogenesis; Infertility; Oogenesis; Ovarian function; PI3K PTEN Akt and TSC mTOR Pathways

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; TUBERIN; MTOR PROTEIN, HUMAN; ONCOPROTEIN; PTEN PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

CELL GROWTH; CELL SURVIVAL; FEMALE INFERTILITY; NONHUMAN; OOCYTE DEVELOPMENT; OVARY FOLLICLE DEVELOPMENT; OVARY INSUFFICIENCY; PRIMORDIAL GERM CELL; REVIEW; SIGNAL TRANSDUCTION; SOMATIC CELL; FEMALE; GENETICS; HUMAN; METABOLISM; OVARY DISEASE; PHYSIOLOGY;

FEMALE; HUMANS; INFERTILITY, FEMALE; ONCOGENE PROTEIN V-AKT; OVARIAN DISEASES; PHOSPHATIDYLINOSITOL 3-KINASES; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

EID: 84908642100     PISSN: 09525041     EISSN: 14796813     Source Type: Journal    
DOI: 10.1530/JME-14-0220     Document Type: Review

References (114)

1. Adhikari D, Flohr G, Gorre N, Shen Y, Yang H, Lundin E, Lan Z, Gambello MJ & Liu K 2009 Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles. Molecular Human Reproduction 15 765-770. (doi: 10.1093/molehr/gap092).
2. Adhikari D, Zheng W, Shen Y, Gorre N, Hamalainen T, Cooney AJ, Huhtaniemi I, Lan Z-H & Liu K 2010 Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Human Molecular Genetics 19 397-410. (doi: 10.1093/hmg/ddp483).
3. Adhikari D, Gorre N, Risal S, Zhao Z, Zhang H, Shen Y & Liu K 2012 The safe use of a PTEN inhibitor for the activation of dormant mouse primordial follicles and generation of fertilizable eggs. PLoS ONE 7 e39034. (doi: 10.1371/journal.pone.0039034).
4. Adhikari D, Risal S, Liu K & Shen Y 2013 Pharmacological inhibition of mTORC1prevents over-activation of the primordial follicle pool in response to elevated PI3K signaling. PLoS ONE 8 e53810. (doi: 10. 1371/journal. pone. 0053810).
5. Alam H, Maizels ET, Park Y, Ghaey S, Feiger ZJ, Chandel NS & Hunzicker-Dunn M 2004 Follicle-stimulating hormone activation of hypoxiainducible factor-1 by the phosphatidyl 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation. Journal of Biological Chemistry 279 19431-19440. (doi: 10. 1074/jbc. M401235200).
6. Albertini DF & Rider V 1994 Patterns of intercellular connectivity in the mammalian cumulus-oocyte complex. Microscopy Research and Technique 27 125-133. (doi: 10. 1002/jemt. 1070270206).
7. Allan CM, Wang Y, Jimenez M, Marshan B, Spaliviero J, Illingworth P & Handelsman DJ 2006 Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice. Journal of Endocrinology 188 549-557. (doi: 10. 1677/joe. 1. 06614).
8. Anderson RA, McLaughlin M, Wallace WH, Albertini DF & Telfer EE 2014 The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence. Human Reproduction 29 97-106. (doi: 10.1093/humrep/det388).
9. Banerjee S, Banerjee S, Saraswat G, Bandyopadhyay SA & Kabir SN 2014 Female reproductive aging is master planned at the level of ovary. PLoS ONE 9 e96210. (doi: 10. 1371/journal. pone. 0096210).
10. Bao B & Garverick HA 1998 Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: a review. Journal of Animal Science 76 1903-1921.
11. Bhartiya D, Sriraman K, Gunjal P & Modak H 2012 Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries? Journal of Ovarian Research 5 32. (doi: 10. 1186/1757-2215-5-32).
12. Bonnet A, Cabau C, Bouchez O, Sarry J, Marsaud N, Foissac S, Woloszyn F, Mulsant P & Mandon Pepin B 2013 An overview of gene expression dynamics during early ovarian folliculogenesis: specificity of follicular compartments and bi-directional dialog. BMC Genomics 14 904. (doi: 10. 1186/1471-2164-14-904).
13. Brown C, LaRocca J, Pietruska J, Ota M, Anderson L, Smith SD, Weston P, Rasoulpour T & Hixon ML 2010 Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKBa/Akt1. Biology of Reproduction 82 246-256. (doi: 10. 1095/biolreprod. 109. 077925).
14. Cahill DJ & Wardle PG 2002 Management of infertility. BMJ 325 28-32. (doi: 10. 1136/bmj. 325. 7354. 28).
15. Cecconi S, Rossi G, Santilli LD, Hoshino Y, Sato E, Palmerini MG & Macchiarelli G 2010 Akt expression in mouse oocytes matured in vivo and in vitro. Reproductive Biomedicine Online 20 35-41. (doi: 10. 1016/j. rbmo. 2009. 10. 011).
16. Chen Y, Jefferson WN, Newbold RR, Padilla-Banks E & Pepling ME 2007 Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology 148 3580-3590. (doi: 10. 1210/en. 2007-0088).
17. Chen Y, Breen K & Pepling ME 2009 Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary. Journal of Endocrinology 202 407-417. (doi: 10. 1677/JOE-09-0109).
18. Choi JY, Jo MW, Lee EY, Yoon BK & Choi DS 2010 The role of autophagy in follicular development and atresia in rat granulosa cells. Fertility and Sterility 93 2532-2537. (doi: 10. 1016/j. fertnstert. 2009. 11. 021).
19. Choi JY, Jo MW, Lee EY & Choi DS 2011 Induction of apoptotic cell death via accumulation of autophagosomes in rat granulosa cells. Fertility and Sterility 95 1482-1486. (doi: 10. 1016/j. fertnstert. 2010. 06. 006).
20. Choi JY, Jo MW, Lee EY & Choi DS 2013 AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia. Reproduction 147 73-80. (doi: 10. 1530/REP-13-0386).
21. Da Silva-Buttkus P, Jayasooriya GS, Mora JM, Mobberley M, Ryder TA, Baithun M, Stark J, Franks S & Hardy K 2008 Effect of cell shape and packing density on granulosa cell proliferation and formation of multiple layers during early follicle development in the ovary. Journal of Cell Science 121 3890-3900. (doi: 10. 1242/jcs. 036400).
22. Fair T, Hulshof SC, Hyttel P, Greve T & Boland M 1997a Nucleus ultrastructure and transcriptional activity of bovine oocytes in preantral and antral follicles. Molecular Reproduction and Development 46 208-215. (doi: 10. 1002/(SICI)1098-2795(199702)46: 2!208:: AIDMRD11O3. 0. CO; 2-X).
23. Fair T, Hulshof SC, Hyttel P, Greve T & Boland M 1997b Oocyte ultrastructure in bovine primordial to early tertiary follicles. Anatomy and Embryology 195 327-336. (doi: 10. 1007/s004290050052).
24. Fakuda S, Orisaka M, Tajima K, Hattori K & Kotsuji F 2009 Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP kinase in bovine theca cells. Journal of Ovarian Research 2 17. (doi: 10. 1186/1757-2215-2-17).
25. Fan HY, Liu Z, Cahill N & Richards JS 2008 Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Molecular Endocrinology 22 2128-2140. (doi: 10. 1210/me. 2008-0095).
26. Farini D, Sala GL, Tedesco M & Felici M 2007 Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells. Developmental Biology 306 572-583. (doi: 10. 1016/j. ydbio. 2007. 03. 031).
27. Fassnacht W, Mempel A, Strowitzki T & Vogt PH 2006 Premature ovarian failure (POF) syndrome: towards the molecular clinical analysis of its genetic complexity. Current Medicinal Chemistry 13 1397-1410. (doi: 10. 2174/092986706776872943).
28. Flanagan JG, Chan DC & Leder P 1991 Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell 64 1025-1035. (doi: 10. 1016/0092-8674(91)90326-T).
29. Fujihara M, Comizzoli P, Keefer CL, Wildt DE & Songsasen N 2014 Epidermal growth factor (EGF) sustains in vitro primordial follicle viability by enhancing stromal cell proliferation via MAPK and PI3K pathways in the prepubertal, but not adult cat ovary. Biology of Reproduction 90 86. (doi: 10. 1095/biolreprod. 113. 115089).
30. Gawriluk TR, Hale AN, Flaws JA, Dhillon CP, Green DR & Rucker EB III 2011 Autophagy is a cell survival program for female germ cells in the murine ovary. Reproduction 141 759-765. (doi: 10. 1530/REP-10-0489).
31. Goto M, Iwase A, Ando H, Kurotsuchi S, Harata T & Kikkawa F 2007 PTEN and Akt expression during growth of human ovarian follicles. Journal of Assisted Reproduction and Genetics 24 541-546. (doi: 10. 1007/s10815-007-9156-3).
32. Goto M, Iwase A, Harata T, Takigawa S, Suzuki K, Manabe S & Kikkawa F 2009 IGF1-induced AKT phosphorylation and cell proliferation are suppressed with the increase in PTEN during luteinization in human granulosa cells. Reproduction 137 835-842. (doi: 10. 1530/REP-08-0315).
33. Greenfeld CR, Pepling ME, Babus JK, Furth PA & Flaws JA 2007 BAX regulates follicular endowment in mice. Reproduction 133 865-876. (doi: 10. 1530/REP-06-0270).
34. Greenseid K, Jindal S, Hurwitz J, Santoro N & Pal L 2011 Granulosa cell gene expression in young women with diminished ovarian reserve. Reproductive Sciences 18 892-899. (doi: 10. 1177/1933719111398502).
35. Gu Y, Runyan C, Shoemaker A, Surani MA & Wylie C 2011 Membranebound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration. PLoS ONE 6 e25984. (doi: 10. 1371/journal. pone. 0025984).
36. Han SJ, Vaccari S, Nedachi T, Andersen CB, Kovacina KS, Roth RA & Conti M 2006 Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. EMBO Journal 25 5716-5725. (doi: 10. 1038/sj. emboj. 7601431).
37. Hatzirodos N, Irving-Rodgers HF, Hummitzsch K, Harland ML, Morris SE & Rodgers RJ 2014 Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes. BMC Genomics 15 24. (doi: 10. 1186/1471-2164-15-24).
38. Hillier SG, Smitz J & Eichenlaub-Ritter U 2010 Folliculogenesis and oogenesis: from basic science to the clinic. Molecular Human Reproduction 16 617-620. (doi: 10.1093/molehr/gaq068).
39. Hoshino Y & Sato E 2008 Protein kinase B (PKB) is required for the completion of meiosis in mouse oocytes. Developmental Biology 314 215-223. (doi: 10. 1016/j. ydbio. 2007. 12. 005).
40. Hoshino Y, Yokoo M, Yoshida N, Sasada H, Matsumoto H & Sato E 2004 Phosphatidylinositol 3-kinase and Akt participate in FSH-induced meiotic maturation of mouse oocytes. Molecular Reproduction and Development 69 77-86. (doi: 10. 1002/mrd. 20150).
41. Huang L, Wang Z-B, Jiang Z-Z, Hu M-W, Lin F, Zhang Q-H, Luo Y-B, Huo Y, ZhaoY, FanH-Y et al. 2013 Specific disruptionofTsc1 inovariangranulosa cells promotes ovulation and causes progressive accumulation of corpora lutea. PLoS ONE 8 e540552. (doi: 10. 1371/journal. pone. 0054052).
42. Huansheng D, Qingjie P, Hanqiong Z, Bo C & Wenbin Y 2011 Estrogen inhibits the early development of mouse follicles through regulating the expression of Kit ligand. Biochemical and Biophysical Research Communications 410 659-664. (doi: 10. 1016/j. bbrc. 2011. 06. 050).
43. Hunzicker-Dunn ME, Lopez-Biladeaua B, Lawa NC, Fiedlerb SE, Carrb DW & Maizelsc ET 2012 PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. PNAS 109 E2979-E2988. (doi: 10. 1073/pnas. 1205661109).
44. Iguchi T, Takasugi N, Bern HA & Mills KT 1986 Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstilbestrol. Teratology 34 29-35. (doi: 10. 1002/tera. 1420340105).
45. Irusta G, Abramovich D, Fernanda P & Tesone M 2010 Direct survival role of vascular endothelial growth factor (VEGF) on rat ovarian follicular cells. Molecular and Cellular Endocrinology 325 93-100. (doi: 10. 1016/j. mce. 2010. 04. 018).
46. Jagarlamudi K, Liu L, Adhikari D, Reddy P, Idahl A, Ottander U, Lundin E & Liu K 2009 Deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation. PLoS ONE 4 e6186. (doi: 10. 1371/journal. pone. 0006186).
47. Jagarlamudi K, Reddy P, Adhikari D & Liu K 2010 Genetically modified mouse models for premature ovarian failure (POF). Molecular and Cellular Endocrinology 315 1-10. (doi: 10. 1016/j. mce. 2009. 07. 016).
48. Jefferson W, Newbold R, Padilla-Banks E & Pepling M 2006 Neonatal genistein treatment alters ovarian differentiation in the mouse: inhibition of oocyte nest breakdown and increased oocyte survival. Biology of Reproduction 74 161-168. (doi: 10. 1095/biolreprod. 105. 045724).
49. Jiang Z-Z, Hu M-W, Wang Z-B, Huang L, Lin F, Qi S-T, Ouyang Y-C, Fan H-Y, Schatten H, Mak TW et al. 2014 Survivin is essential for fertile egg production and female fertility in mice. Cell Death & Disease 5 e1154. (doi: 10. 1038/cddis. 2014. 126).
50. John GB, Shirley LJ, Gallardo TD & Castrillon DH 2007 Specificity of the requirement for Foxo3 in primordial follicle activation. Reproduction 133 855-863. (doi: 10. 1530/REP-06-0051).
51. John GB, Gallardo TD, Shirley LJ & Castrillon DH 2008 Foxo3 is a PI3Kdependent molecular switch controlling the initiation of oocyte growth. Developmental Biology 321 197-204. (doi: 10. 1016/j. ydbio. 2008. 06. 017).
52. John GB, Shidler MJ, Besmer P & Castrillon DH 2009 Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation. Developmental Biology 331 292-299. (doi: 10. 1016/j. ydbio. 2009. 05. 546).
53. Jumayev I, Harun-Or-Rashid M, Rustamov O, Zakirova N, Kasuya H & Sakamoto J 2012 Social correlates of female infertility in Uzbekistan. Nagoya Journal of Medical Science 74 273-283.
54. Kalous J, Solc P, Baran V, Kubelka M, Schultz RM & Motlik J 2006 PKB/AKT is involved in resumption of meiosis in mouse oocytes. Biology of the Cell 98 111-123. (doi: 10. 1042/BC20050020).
55. Kalous J, Kubelka M, Šolc P, Šušor A & Motlík J 2009 AKT (protein kinase B) is implicated in meiotic maturation of porcine oocytes. Reproduction 138 645-654. (doi: 10. 1530/REP-08-0461).
56. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho C-H, Kawamura N, Tamura M, Hashimoto S et al. 2013 Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. PNAS 110 17474-17479. (doi: 10. 1073/pnas. 1312830110).
57. Kimura T, Tomooka M, Yamano N, Murayama K, Matoba S, Umehara H, Kanai Y & Nakano T 2008 AKT signaling promotes derivation of embryonic germ cells from primordial germ cells. Development 135 869-879. (doi: 10. 1242/dev. 013474).
58. Klinge CM 2001 Estrogen receptor interaction with estrogen response elements. Nucleic Acids Research 29 2905-2919. (doi: 10.1093/nar/29. 14. 2905).
59. Kogasaka Y, Hoshino Y, Tanemura K & Sato E 2013 Distribution and association of mTOR with its cofactors, raptor and rictor, in cumulus cells and oocytes during meiotic maturation in mice. Molecular Reproduction and Development 80 334-348. (doi: 10. 1002/mrd. 22166).
60. Laplante M & Sabatini DM 2012 mTOR signaling in growth control and disease. Cell 149 274-293. (doi: 10. 1016/j. cell. 2012. 03. 017).
61. La Sala G, Farini D & De Felici M 2010 Rapid estrogen signaling in mouse primordial germ cells. Experimental Cell Research 316 1716-1727. (doi: 10. 1016/j. yexcr. 2010. 03. 024).
62. Lee SE, Sun SC, Choi HY, UhmSJ & Kim NH 2012 mTOR is required for asymmetric division through small GTPases in mouse oocytes. Molecular Reproduction and Development 79 356-366. (doi: 10. 1002/mrd. 22035).
63. Lei L & Spradling AC 2013 Mouse primordial germ cells produce cysts that partially fragment prior to meiosis. Development 140 2075-2081. (doi: 10. 1242/dev. 093864).
64. Li J, Kawamurab K, Chenga Y, Liuc S, Kleina C, Liuc S, Duanc E-K & Hsueha AJ 2010 Activation of dormant ovarian follicles to generate mature eggs. PNAS 107 10280-10284. (doi: 10. 1073/pnas. 1001198107).
65. Liu L, Rajareddy S, Reddy P, Du C, Jagarlamudi K, Shen Y, Gunnarsson D, Selstam G, Boman K & Liu K 2007 Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a. Development 134 199-209. (doi: 10. 1242/dev. 02667).
66. Liu Z, Castrillon DH, Zhou W & Richards JS 2013 FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH. Molecular Endocrinology 27 238-252. (doi: 10. 1210/me. 2012-1296).
67. Mack EM, Smith JE, Kurz SG & Wood JR 2012 cAMP-dependent regulation of ovulatory response genes is amplified by IGF1 due to synergistic effects on Akt phosphorylation and NF-kB transcription factors. Reproduction 144 595-602. (doi: 10. 1530/REP-12-0225).
68. ManiAM, FenwickMA, ChengZ, SharmaMK, SinghD&WathesDC2010IGF1 induces up-regulation of steroidogenic and apoptotic regulatory genes via activation of Phosphatidylinositol-dependent kinase/AKT in bovine granulosa cells. Reproduction 139 139-151. (doi: 10. 1530/REP-09-0050).
69. Manning BD & Cantley LC 2007 AKT/PKB signaling: navigating downstream. Cell 129 1261-1274. (doi: 10. 1016/j. cell. 2007. 06. 009).
70. Manosalva I, González A & Kageyama R 2012 Hes1 in the somatic cells of the murine ovary is necessary for oocyte survival and maturation. Developmental Biology 375 140-151. (doi: 10. 1016/j. ydbio. 2012. 12. 015).
71. Markholt S, Grondahl ML, Ernst EH, Andersen CY, Ernst E & Lykke-Hartmann K 2012 Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction. Molecular Human Reproduction 18 96-110. (doi: 10.1093/molehr/gar083).
72. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S & Stevens GA 2012 National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Medicine 9 e1001356. (doi: 10. 1371/journal. pmed. 1001356).
73. Mayer S, Wrenzycki C & Tomek W 2014 Inactivation of mTOR arrests bovine oocytes in the metaphase-I stage, despite reversible inhibition 4E-BP1 phosphorylation. Molecular Reproduction and Development 81 363-375. (doi: 10. 1002/mrd. 22305).
74. McCoshen JA & McCallion DJ 1975 A study of the primordial germ cells during their migratory phase in steel mutant mice. Experientia 31 589-590. (doi: 10. 1007/BF01932475).
75. McLaughlin M, Patrizio P, Kayisli U, Luk J, Thomson TC, Anderson RA, Telfer EE & Johnson J 2011 mTOR kinase inhibition results in oocyte loss characterized by empty follicles in human ovarian cortical strips cultured in vitro. Fertility and Sterility 96 1154-1159. (doi: 10. 1016/j. fertnstert. 2011. 08. 040).
76. McLaughlin M, Kinnell HL, Anderson RA & Telfer EE 2014 Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles. Molecular Human Reproduction 20 736-744. (doi: 10.1093/molehr/gau037).
77. McNatty KP, Reader K, Smith P, Heath DA & Juengel JL 2007 Control of ovarian follicular development to the gonadotrophin-dependent phase: a 2006 perspective. Society of Reproduction and Fertility Supplement 64 55-68.
78. Mork L, Tang H, Batchvarov I & Capel B 2012 Mouse germ cell clusters form by aggregation as well as clonal divisions. Mechanisms of Development 128 591-596. (doi: 10. 1016/j. mod. 2011. 12. 005).
79. PalaniappanM& Menon KM 2012 Luteinizing hormone/human chorionic gonadotropin-mediated activation of mTORC1 signaling is required for androgen synthesis by thecal-interstitial cells. Molecular Endocrinology 26 1732-1742. (doi: 10. 1210/me. 2012-1106).
80. Palaniappan M, Menon B & Menon KM 2013 Stimulatory effect of insulin on theca-interstitial cell proliferation and cell cycle regulatory proteins through MTORC1 dependent pathway. Molecular and Cellular Endocrinology 366 81-89. (doi: 10. 1016/j. mce. 2012. 12. 004).
81. Pelosi E, Omari S, Michel M, Ding J, Amano T, Forabosco A, Schlessinger D & Ottolenghi C 2013 Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nature Communications 4 1843. (doi: 10. 1038/ncomms2861).
82. Pepling ME, Willhelm JE, O'Hara AL, Gephardt GW & Spradling AC 2007 Mouse oocytes within germ cell cysts and primordial follicles contain a Balbiani body. PNAS 104 187-192. (doi: 10. 1073/pnas. 0609923104).
83. Peters H, Byskov AG, Himelstein-Braw R & Faber M1975 Follicular growth: the basic event in the mouse and human ovary. Journal of Reproduction and Fertility 45 559-566. (doi: 10. 1530/jrf. 0. 0450559).
84. Piotrowska H, Kempisty B, Sosinska P, Ciesiolka S, Bukowska D, Antosik P, Rybska M, Brussow KP, Nowicki M & Zabel M 2013 The role TGF superfamily gene expression in the regulation of folliculogenesis and oogenesis in mammals: a review. Veterinarni Medicina 10 505-515.
85. Pisarska MD, Kuo F-T, Tang D, Zarrini P, Khan S & Ketefian A 2009 Expression of forkhead transcription factors in human granulosa cells. Fertility and Sterility 91 1392-1394. (doi: 10. 1016/j. fertnstert. 2008. 04. 054).
86. Rao JU, Shah KB, Puttaiah J & Rudraiah M 2011 Gene expression profiling of preovulatory follicle in the buffalo cow: effects of increased IGF-I concentration on periovulatory events. PLoS ONE 6 e20754. (doi: 10. 1371/journal. pone. 0020754).
87. Reddy P, Shen L, Ren C, Boman K, Lundin E, Ottander U, Lindgren P, Liu YX, Sun QY & Liu K 2005 Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Developmental Biology 281 160-170. (doi: 10. 1016/j. ydbio. 2005. 02. 013).
88. Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, Du C, Tang W, Hamalainen T, Peng SL et al. 2008 Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 319 611-613. (doi: 10. 1126/science. 1152257).
89. Reddy P, Adhikari D, Zheng W, Liang S, Hamalainen T, Tohonen V, Ogawa W, Noda T, Volarevic S, Huhtaniemi I et al. 2009 PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Human Molecular Genetics 18 2813-2824. (doi: 10.1093/hmg/ddp217).
90. Romasko EJ, Amarnath D, Midic U & Latham KE 2013 Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals. Genetics 195 349-358. (doi: 10. 1534/genetics. 113. 154005).
91. Ryan KE, Glister C, Lonergan P, Martin F, Knight PG & Evans AC 2008 Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep. Journal of Ovarian Research 1 2. (doi: 10. 1186/1757-2215-1-2).
92. Smith MF, McIntush EW & Smith GW 1994 Mechanisms associated with corpus luteum development. Journal of Animal Science 72 1857-1872.
93. Su Y-Q, Wu X, O'Brien MJ, Pendola FL, Denegre JN, Matzuk MM & Eppig JJ 2004 Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop. Developmental Biology 276 64-73. (doi: 10. 1016/j. ydbio. 2004. 08. 020).
94. Sugiura K, Pendola FL & Epigg JJ 2005 Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Developmental Biology 279 20-30. (doi: 10. 1016/j. ydbio. 2004. 11. 027).
95. Tanaka Y, Park JH, Tanwar PS, Kaneko-Tarui T, Mittal S, Lee H-J & Teixeira JM 2012 Deletion of tuberous sclerosis 1 in somatic cells of the murine reproductive tract causes female infertility. Endocrinology 153 404-416. (doi: 10. 1210/en. 2011-1191).
96. Tarnawa ED, Baker MD, Aloisio G, Carr BR & Castrillon DH 2013 Gonadal expression of Foxo1, but not Foxo3, is conserved in diverse mammalian species. Biology of Reproduction 88 103. (doi: 10. 1095/biolreprod. 112. 105791).
97. Thomas FH & Vanderhyden BC 2006 Oocyte-granulosa cell interactions during mouse follicular development: regulation of kit ligand expression and its role in oocyte growth. Reproductive Biology and Endocrinology 4 19. (doi: 10. 1186/1477-7827-4-19).
98. Tingen CM, Bristol-Gould SK, Kiesewetter SE, Wellington JT, Shea L & Woodruff TK 2009 Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. Biology of Reproduction 81 16-25. (doi: 10. 1095/biolreprod. 108. 074898).
99. Tomek W & Smiljakovic T 2005 Activation of Akt (protein kinase B) stimulates metaphase I to metaphase II transition in bovine oocytes. Reproduction 130 423-430. (doi: 10. 1530/rep. 1. 00754).
100. TuckAR, MottersheadDG, FernandesHA, NormanRJ, TilleyWD, RobkerRL& Hickey TE 2014 Mouse GDF9 decreases KITL gene expression in human granulosa cells. Endocrine (In Press). (doi: 10. 1007/s12020-014-0335-6).
101. Vaccari S, Horner K, Mehlmann LM & Conti M 2008 Generation of mouse oocytes defective in cAMP synthesis and degradation: endogenous cyclic AMP is essential for meiotic arrest. Developmental Biology 316 124-134. (doi: 10. 1016/j. ydbio. 2008. 01. 018).
102. Vadlakonda L, Dash A, Pasupuleti M, Anil Kumar K & Reddanna P 2013 The paradox of Akt-mTOR interactions. Frontiers in Oncology 3 article 165. (doi: 10. 3389/fonc. 2013. 00165).
103. Wang X-L, Wu Y, Tan L-B, Tian Z, Liu J-H, Zhu D-S & Zeng S-M 2012 Follicle-stimulating hormone regulates pro-apoptotic protein Bcl-2-interacting mediator of cell death-extra long (BimEL)-induced porcine granulosa cell apoptosis. Journal of Biological Chemistry 287 10166-10177. (doi: 10. 1074/jbc. M111. 293274).
104. Wang Z-P, Mu X-Y, GuoM, Wang Y-J, Teng Z, Mao G-P, Niu W-B, Feng L-Z, Zhao L-H & Xia G-L 2014 Transforming growth factor-b signaling participates in the maintenance of the primordial follicle pool in the mouse ovary. Journal of Biological Chemistry 289 8299-8311. (doi: 10. 1074/jbc. M113. 532952).
105. Watkins WJ, Umbers AJ, Woad KJ, Harris SE, Winship IM, Gersak K & Shelling AN 2006 Mutational screening of FOXO3A and FOXO1A in women with premature ovarian failure. Fertility and Sterility 86 1518-1521. (doi: 10. 1016/j. fertnstert. 2006. 03. 054).
106. Wullschleger S, Loewith R & Hall MN 2006 TOR signaling in growth and metabolism. Cell 124 471-484. (doi: 10. 1016/j. cell. 2006. 01. 016).
107. Xu Z, Garverick HA, Smith GW, Smith MF, Hamilton SA & Youngquist RS 1995 Expression of follicle-stimulating hormone and luteinizing hormone receptor messenger ribonucleic acids in bovine follicles during the first follicular wave. Biology of Reproduction 53 951-957. (doi: 10. 1095/biolreprod53. 4. 951).
108. Yaba A, Bianchi V, Borini A &Johnson J 2008 A putativemitotic checkpoint dependent on mTOR function controls cell proliferation and survival in ovarian granulosa cells. Reproductive Sciences 15 128-138. (doi: 10. 1177/1933719107312037).
109. Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL et al. 2001 Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Molecular Endocrinology 15 854-866. (doi: 10. 1210/mend. 15. 6. 0662).
110. Yu J, Yaba A, Kasiman C, Thomson T & Johnson J 2011 mTOR controls ovarian follicle growth by regulating granulosa cell proliferation. PLoS ONE 6 e21415. (doi: 10. 1371/journal. pone. 0021415).
111. Zama AM & UzumcuM2013 Targeted genome-widemethylation and gene expression analyses reveal signaling pathways involved in ovarian dysfunction after developmental EDC exposure in rats. Biology of Reproduction 88 1-13. (doi: 10. 1095/biolreprod. 112. 104802).
112. Zhang C, Guo L, Zhu B, Feng Y, Yu S, An N & Wang X 2013a Effects of 3, 5, 30-triiodothyronine (T3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells. Chinese Journal of Physiology 56 298-305. (doi: 10. 4077/CJP. 2013. BAC194).
113. Zhang XM, Li L, Xu JJ, Wang N, Liu WJ, Lin XH, Fu YC & Luo LL 2013b Rapamycin preserves the follicle pool reserve and prolongs the ovarian lifespan of female rats via modulating mTOR activation and sirtuin expression. Gene 523 82-87. (doi: 10. 1016/j. gene. 2013. 03. 039).
114. Zheng W, Zhang H, Gorre N, Risal S, Shen Y & Liu K 2014 Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions. Human Molecular Genetics 23 920-928. (doi: 10.1093/hmg/ddt486).