Top

Journal of Ovarian Research

Published in:

Open Access 01-12-2014 | Research

Primordial follicle activation in the ovary of Ames dwarf mice

Authors: Augusto Schneider, Xu Zhi, Fabiana Moreira, Thomaz Lucia, Rafael Gianella Mondadori, Michal M Masternak

Published in: Journal of Ovarian Research | Issue 1/2014

Abstract

Background

The insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt1), Forkhead Box O3a (FOXO3a) pathway is directly involved in aging and ovarian activation of follicle growth. Therefore, the aim of this work was to measure the expression of genes related to the ovarian pathway for activation of primordial follicles and FOXO3a protein phosphorylation between young and old female Ames dwarf (df/df) and normal (N) mice.

Methods

For this study ovaries from N (n = 10) and df/df (n = 10) female mice were collected at 5–6 months of age and at 21–22 months of age. For immunohistochemistry ovaries from 12 month-old and df/df mice were used.

Results

The expression of Irs1, Pi3k, Akt1, mammalian target of rapamycin (Mtor), suppressor of cytokine signaling −2 (Socs2), Socs3 was lower (P < 0.05) in older than younger N mice and not different (P > 0.05) between young and old df/df mice. The expression of Foxo3a was also lower (P < 0.05) in old than younger N and df/df mice and was higher (P < 0.05) in old df/df than N mice. Expression of Amh was lower (P < 0.05) in old than young N and df/df mice and was higher (P = 0.0009) in df/df than N mice. Imunnostaining for p-FOXO3 was lower in df/df than N mice (P < 0.001), although FOXO3 immunostaining was not different (P > 0.05) between df/df and N mice.

Conclusions

In sum, the present study indicates that lower expression of Irs1, Socs2, Socs3, Akt1, Pi3k, Mtor and Foxo3a mRNA in the ovaries of older mice of both genotypes is associated to a reduced ovarian activity revealed by lower expression of Amh mRNA. At the same time, ovaries of old df/df mice maintained higher expression of Foxo3a mRNA, which was associated to higher ovarian activity. We have shown that df/df females have a lower level of p-FOXO3 in oocytes from primordial/primary follicles, an important activator of follicular growth. Therefore, this study strongly indicates that Prop1^df mutation causes delayed ovarian aging.

Available only for authorised users

Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O'Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Andersen B, Beamer WG, Rosenfeld MG: Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 1996, 384: 327–333. 10.1038/384327a0CrossRefPubMed

Bartke A, Brown-Borg H, Mattison J, Kinney B, Hauck S, Wright C: Prolonged longevity of hypopituitary dwarf mice. Exp Gerontol 2001, 36: 21–28. 10.1016/S0531-5565(00)00205-9CrossRefPubMed

Chandrashekar V, Bartke A: Induction of endogenous insulin-like growth factor-I secretion alters the hypothalamic-pituitary-testicular function in growth hormone-deficient adult dwarf mice. Biol Reprod 1993, 48: 544–551. 10.1095/biolreprod48.3.544CrossRefPubMed

Brown-Borg HM, Borg KE, Meliska CJ, Bartke A: Dwarf mice and the ageing process. Nature 1996, 384: 33. 10.1038/384033a0CrossRefPubMed

Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ: Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 2003, 144: 3799–3810. 10.1210/en.2003-0374CrossRefPubMed

Masoro EJ: Overview of caloric restriction and ageing. Mech Ageing Dev 2005, 126: 913–922. 10.1016/j.mad.2005.03.012CrossRefPubMed

Bartke A, Chandrashekar V, Bailey B, Zaczek D, Turyn D: Consequences of growth hormone (GH) overexpression and GH resistance. Neuropeptides 2002, 36: 201–208. 10.1054/npep.2002.0889CrossRefPubMed

Panici JA, Harper JM, Miller RA, Bartke A, Spong A, Masternak MM: Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice. FASEB J 2010, 24: 5073–5079. 10.1096/fj.10-163253PubMedCentralCrossRefPubMed

Barbieri M, Bonafe M, Franceschi C, Paolisso G: Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 2003, 285: E1064–1071. 10.1152/ajpendo.00296.2003CrossRefPubMed

10.

Sun LY, Al-Regaiey K, Masternak MM, Wang J, Bartke A: Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice. Neurobiol Aging 2005, 26: 929–937. 10.1016/j.neurobiolaging.2004.07.010CrossRefPubMed

11.

Schneider A, Zhi X, Bartke A, Kopchick JJ, Masternak MM: Effect of growth hormone receptor gene disruption and PMA treatment on the expression of genes involved in primordial follicle activation in mice ovaries. Age 2014, 36: 9701. 10.1007/s11357-014-9701-9PubMedCentralCrossRefPubMed

12.

Chandrashekar V, Zaczek D, Bartke A: The consequences of altered somatotropic system on reproduction. Biol Reprod 2004, 71: 17–27. 10.1095/biolreprod.103.027060CrossRefPubMed

13.

Bartke A: Reproduction of female dwarf mice treated with prolactin. J Reprod Fertil 1966, 11: 203–206. 10.1530/jrf.0.0110203CrossRefPubMed

14.

Tang K, Bartke A, Gardiner CS, Wagner TE, Yun JS: Gonadotropin secretion, synthesis, and gene expression in human growth hormone transgenic mice and in Ames dwarf mice. Endocrinology 1993, 132: 2518–2524.PubMed

15.

Bachelot A: Growth Hormone Is Required for Ovarian Follicular Growth. Endocrinology 2002, 143: 4104–4112. 10.1210/en.2002-220087CrossRefPubMed

16.

Li L, Fu YC, Xu JJ, Chen XC, Lin XH, Luo LL: Caloric restriction promotes the reproductive capacity of female rats via modulating the level of insulin-like growth factor-1 (IGF-1). Gen Comp Endocrinol 2011, 174: 232–237. 10.1016/j.ygcen.2011.09.005CrossRefPubMed

17.

Sluczanowska-Glabowska S, Laszczynska M, Piotrowska K, Glabowski W, Kopchick JJ, Bartke A, Kucia M, Ratajczak MZ: Morphology of ovaries in laron dwarf mice, with low circulating plasma levels of insulin-like growth factor-1 (IGF-1), and in bovine GH-transgenic mice, with high circulating plasma levels of IGF-1. J Ovarian Res 2012, 5: 18. 10.1186/1757-2215-5-18PubMedCentralCrossRefPubMed

18.

Slot KA, Kastelijn J, Bachelot A, Kelly PA, Binart N, Teerds KJ: Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice. Reproduction 2006, 131: 525–532. 10.1530/rep.1.00946CrossRefPubMed

19.

McGee EA, Hsueh AJ: Initial and cyclic recruitment of ovarian follicles. Endocr Rev 2000, 21: 200–214.PubMed

20.

Brown C, LaRocca J, Pietruska J, Ota M, Anderson L, Smith SD, Weston P, Rasoulpour T, Hixon ML: Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1. Biol Reprod 2010, 82: 246–256. 10.1095/biolreprod.109.077925CrossRefPubMed

21.

Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, Du C, Tang W, Hamalainen T, Peng SL, Lan ZJ, Cooney AJ, Huhtaniemi I, Liu K: Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 2008, 319: 611–613. 10.1126/science.1152257CrossRefPubMed

22.

Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA: Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 2003, 301: 215–218. 10.1126/science.1086336CrossRefPubMed

23.

Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, Wolf I, Kanety H, Sredni B, Meirow D: Cyclophosphamide triggers follicle activation and "burnout"; AS101 prevents follicle loss and preserves fertility. Sci Transl Med 2013, 5: 185ra-162.

24.

Caron E, Ghosh S, Matsuoka Y, Ashton-Beaucage D, Therrien M, Lemieux S, Perreault C, Roux PP, Kitano H: A comprehensive map of the mTOR signaling network. Mol Syst Biol 2010, 6: 453. 10.1038/msb.2010.108PubMedCentralCrossRefPubMed

25.

Adhikari D, Zheng W, Shen Y, Gorre N, Hamalainen T, Cooney AJ, Huhtaniemi I, Lan ZJ, Liu K: Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet 2010, 19: 397–410. 10.1093/hmg/ddp483PubMedCentralCrossRefPubMed

26.

Bartke A: Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings. Aging Cell 2008, 7: 285–290. 10.1111/j.1474-9726.2008.00387.xCrossRefPubMed

27.

Masternak MM, Al-Regaiey K, Bonkowski MS, Panici J, Sun L, Wang J, Przybylski GK, Bartke A: Divergent effects of caloric restriction on gene expression in normal and long-lived mice. J Gerontol A Biol Sci Med Sci 2004, 59: 784–788. 10.1093/gerona/59.8.B784CrossRefPubMed

28.

Masternak MM, Al-Regaiey KA, Del Rosario Lim MM, Bonkowski MS, Panici JA, Przybylski GK, Bartke A: Caloric restriction results in decreased expression of peroxisome proliferator-activated receptor superfamily in muscle of normal and long-lived growth hormone receptor/binding protein knockout mice. J Gerontol A Biol Sci Med Sci 2005, 60: 1238–1245. 10.1093/gerona/60.10.1238CrossRefPubMed

29.

Silva RC, Bao SN, Jivago JL, Lucci CM: Ultrastructural characterization of porcine oocytes and adjacent follicular cells during follicle development: lipid component evolution. Theriogenology 2011, 76: 1647–1657. 10.1016/j.theriogenology.2011.06.029CrossRefPubMed

30.

Atkin G, Barber PR, Vojnovic B, Daley FM, Glynne-Jones R, Wilson GD: Correlation of spectral imaging and visual grading for the quantification of thymidylate synthase protein expression in rectal cancer. Hum Pathol 2005, 36: 1302–1308. 10.1016/j.humpath.2005.08.016CrossRefPubMed

31.

Di Cataldo S, Ficarra E, Macii E: Computer-aided techniques for chromogenic immunohistochemistry: status and directions. Comput Biol Med 2012, 42: 1012–1025. 10.1016/j.compbiomed.2012.08.004CrossRefPubMed

32.

Melendez-Ferro M, Rice MW, Roberts RC, Perez-Costas E: Dual use of immunohistochemistry for film densitometry and light microscopy. J Neurosci Methods 2012, 208: 86–91. 10.1016/j.jneumeth.2012.05.003PubMedCentralCrossRefPubMed

33.

Moreira F, Corcini CD, Mondadori RG, Gevehr-Fernandes C, Mendes FF, Araujo EG, Lucia T Jr: Leptin and mitogen-activated protein kinase (MAPK) in oocytes of sows and gilts. Anim Reprod Sci 2013, 139: 89–94. 10.1016/j.anireprosci.2013.03.011CrossRefPubMed

34.

Liu L, Rajareddy S, Reddy P, Du C, Jagarlamudi K, Shen Y, Gunnarsson D, Selstam G, Boman K, Liu K: Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a. Development 2007, 134: 199–209. 10.1242/dev.02667CrossRefPubMed

35.

Jeppesen JV, Anderson RA, Kelsey TW, Christiansen SL, Kristensen SG, Jayaprakasan K, Raine-Fenning N, Campbell BK, Yding Andersen C: Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 2013, 19: 519–527. 10.1093/molehr/gat024CrossRefPubMed

36.

Visser JA, de Jong FH, Laven JS, Themmen AP: Anti-Mullerian hormone: a new marker for ovarian function. Reproduction 2006, 131: 1–9. 10.1530/rep.1.00529CrossRefPubMed

37.

McGrath SA, Esquela AF, Lee SJ: Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 1995, 9: 131–136.PubMed

38.

Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM: The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 1998, 12: 1809–1817. 10.1210/mend.12.12.0206CrossRefPubMed

39.

Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM: Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 1996, 383: 531–535. 10.1038/383531a0CrossRefPubMed

40.

Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM: Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 2001, 15: 854–866. 10.1210/mend.15.6.0662CrossRefPubMed

41.

Pelosi E, Omari S, Michel M, Ding J, Amano T, Forabosco A, Schlessinger D, Ottolenghi C: Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nat Commun 2013, 4: 1843. 10.1038/ncomms2861PubMedCentralCrossRefPubMed

42.

Le Roith D, Bondy C, Yakar S, Liu JL, Butler A: The somatomedin hypothesis: 2001. Endocr Rev 2001, 22: 53–74. 10.1210/edrv.22.1.0419CrossRefPubMed

43.

Liu JL, Yakar S, LeRoith D: Conditional knockout of mouse insulin-like growth factor-1 gene using the Cre/loxP system. Proc Soc Exp Biol Med 2000, 223: 344–351. 10.1046/j.1525-1373.2000.22349.xCrossRefPubMed

44.

Baker J, Hardy MP, Zhou J, Bondy C, Lupu F, Bellve AR, Efstratiadis A: Effects of an Igf1 gene null mutation on mouse reproduction. Mol Endocrinol 1996, 10: 903–918.PubMed

Title: Primordial follicle activation in the ovary of Ames dwarf mice
Authors: Augusto Schneider
Xu Zhi
Fabiana Moreira
Thomaz Lucia
Rafael Gianella Mondadori
Michal M Masternak
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-014-0120-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Primordial follicle activation in the ovary of Ames dwarf mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Down-regulated aquaporin 5 inhibits proliferation and migration of human epithelial ovarian cancer 3AO cells

Stereotactic radiotherapy in epithelial ovarian cancer brain metastases patients

Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular risk in patients with polycystic ovary syndrome

RETRACTED ARTICLE: Risk miRNA screening of ovarian cancer based on miRNA functional synergistic network

Plasma concentrations of D-dimer and outcome of in vitro fertilization

The expression of the Sprouty 1 protein inversely correlates with growth, proliferation, migration and invasion of ovarian cancer cells