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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Analysis of in vitro follicle development during the onset of premature ovarian insufficiency in a mouse model

Heidy Kaune A B , Sairah Sheikh A and Suzannah A. Williams A
+ Author Affiliations
- Author Affiliations

A Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women’s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK.

B Facultad de Medicina, Universidad Diego Portales, Santiago, Chile.

C Corresponding author. Email: suzannah.williams@obs-gyn.ox.ac.uk

Reproduction, Fertility and Development 29(8) 1538-1544 https://doi.org/10.1071/RD15524
Submitted: 12 December 2015  Accepted: 24 June 2016   Published: 22 September 2016

Abstract

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years of age and is predominantly idiopathic. In a transgenic mouse model of follicular POI, the Double Mutant (DM), female mice are fertile at 6 weeks of age, become infertile by 9 weeks and exhibit POI by 3 months. DM female mice generate oocytes lacking mucin O-glycans and complex N-glycans due to deletion of core 1 synthase, glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1galt1) and mannoside acetylglucosaminyltransferase 1 (Mgat1) respectively (DM, C1galt1F/FMgat1F/F:ZP3Cre; Control, C1galt1F/FMgat1F/F). To determine whether DM follicle development could be improved in a controlled environment, follicles from DM and Control mice were cultured individually and follicle growth, morphology, survival and antrum formation were evaluated. DM ovaries were more rigid than Control ovaries at 3, 6 and 9 weeks, which was exacerbated with age, resulting in a failure to isolate follicles from 9 week-old DM females. DM follicles had decreased survival compared with Control follicles from females at 3 and 6 weeks of age. Furthermore, survival rate of DM follicles decreased with age between 3 and 6 weeks. DM follicles at both 3 and 6 weeks had accelerated follicle growth and altered antrum formation during the first few days of culture but, after 6 days, follicles were equivalent in size to the Controls. In conclusion, a population of DM follicles retain the potential to develop in vitro, and therefore follicle culture offers a reliable method to generate antral follicles from preantral follicles after the onset of POI in these female mice.

Additional keywords: extracellular matrix, tissue rigidity.


References

Andersen, M. M., Kroll, J., Byskov, A. G., and Faber, M. (1976). Protein composition in the fluid of individual bovine follicles. J. Reprod. Fertil. 48, 109–118.
Protein composition in the fluid of individual bovine follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2sXisl2rsA%3D%3D&md5=1f6d0627a9b2f32f05e0e954fa03380eCAS | 966215PubMed |

Axford, J. (2001). The impact of glycobiology on medicine. Trends Immunol. 22, 237–239.
The impact of glycobiology on medicine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktFahur4%3D&md5=4839439faac9cdf19cd2a2d814cd6dacCAS | 11323271PubMed |

Baker, S. J., Srsen, V., Lapping, R., and Spears, N. (2001). Combined effect of follicle–follicle interactions and declining follicle-stimulating hormone on murine follicle health in vitro. Biol. Reprod. 65, 1304–1310.
Combined effect of follicle–follicle interactions and declining follicle-stimulating hormone on murine follicle health in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnt1Cmsbg%3D&md5=6babc30ef57ed6e211e2899f2328cd42CAS | 11566757PubMed |

Bender, K., Walsh, S., Evans, A. C., Fair, T., and Brennan, L. (2010). Metabolite concentrations in follicular fluid may explain differences in fertility between heifers and lactating cows. Reproduction 139, 1047–1055.
Metabolite concentrations in follicular fluid may explain differences in fertility between heifers and lactating cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXns12qsbs%3D&md5=ebb6bd630b0f0a1e9f1494d40f48f29fCAS | 20385782PubMed |

Christensen, A. P., Patel, S. H., Grasa, P., Christian, H. C., and Williams, S. A. (2015). Oocyte glycoproteins regulate the form and function of the follicle basal lamina and theca cells. Dev. Biol. 401, 287–298.
Oocyte glycoproteins regulate the form and function of the follicle basal lamina and theca cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXmtlSqtg%3D%3D&md5=d2b28bfbc293c8def3bf2c7d5cbf8b6aCAS | 25557622PubMed |

Coulam, C. B., Adamson, S. C., and Annegers, J. F. (1986). Incidence of premature ovarian failure. Obstet. Gynecol. 67, 604–606.
| 1:STN:280:DyaL287nsF2isQ%3D%3D&md5=38ab1237bef24233b49bd431e82328a1CAS | 3960433PubMed |

Cristol, P., Chabab, A., Diafouka, F., Flandre, O., Bressot, N., Cristol, A. M., Hedon, B., Deschamps, F., and Gelis, M. T. (1985). [Pregnancies by fertilization in vitro. Biochemistry of the follicular fluid.] Pathol. Biol. (Paris) 33, 155–161.
| 1:STN:280:DyaL2M3ktFOluw%3D%3D&md5=ecfa055b99e63fb2a9f1065bce5518bbCAS | 3892441PubMed |

Das, M., Gillott, D. J., Saridogan, E., and Djahanbakhch, O. (2008). Anti-Mullerian hormone is increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome. Hum. Reprod. 23, 2122–2126.
Anti-Mullerian hormone is increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtF2qtb%2FL&md5=060eac4e24989a311131048774893014CAS | 18550512PubMed |

Davidson, B., Murray, A. A., Elfick, A., and Spears, N. (2013). Raman micro-spectroscopy can be used to investigate the developmental stage of the mouse oocyte. PLoS One 8, e67972.
Raman micro-spectroscopy can be used to investigate the developmental stage of the mouse oocyte.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtFarsrjM&md5=1037c5d4d0bc9d726ef5560af76e4253CAS | 23840882PubMed |

Grasa, P., Kaune, H., and Williams, S. A. (2012). Embryos generated from oocytes lacking complex N- and O-glycans have compromised development and implantation. Reproduction 144, 455–465.
Embryos generated from oocytes lacking complex N- and O-glycans have compromised development and implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFGru7rI&md5=23110abc22c32740c769bcedf05034edCAS | 22919046PubMed |

Grasa, P., Ploutarchou, P., and Williams, S. A. (2015). Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9 : BMP15 expression. FASEB J. 29, 525–539.
Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9 : BMP15 expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXislGjurc%3D&md5=91221c8a2f3433af2787f7abd831dee4CAS | 25416550PubMed |

Grimek, H. J., Bellin, M. E., and Ax, R. L. (1984). Characteristics of proteoglycans isolated from small and large bovine ovarian follicles. Biol. Reprod. 30, 397–409.
Characteristics of proteoglycans isolated from small and large bovine ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXhtlCls7o%3D&md5=2db29747bd18c486d8c58e10949daa66CAS | 6423006PubMed |

Hornick, J. E., Duncan, F. E., Shea, L. D., and Woodruff, T. K. (2012). Isolated primate primordial follicles require a rigid physical environment to survive and grow in vitro. Hum. Reprod. 27, 1801–1810.
Isolated primate primordial follicles require a rigid physical environment to survive and grow in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XnvVOls7k%3D&md5=45c50265a36650f3f029defd4c3dde13CAS | 22456922PubMed |

Hughesdon, P. E. (1982). Morphology and morphogenesis of the Stein–Leventhal ovary and of so-called ‘hyperthecosis’. Obstet. Gynecol. Surv. 37, 59–77.
Morphology and morphogenesis of the Stein–Leventhal ovary and of so-called ‘hyperthecosis’.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL387gsVOhtA%3D%3D&md5=d3609795b02053d42af736ddb808ca68CAS | 7033852PubMed |

Mendoza, C., Ruiz-Requena, E., Ortega, E., Cremades, N., Martinez, F., Bernabeu, R., Greco, E., and Tesarik, J. (2002). Follicular fluid markers of oocyte developmental potential. Hum. Reprod. 17, 1017–1022.
Follicular fluid markers of oocyte developmental potential.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xjs12isLk%3D&md5=dd9bc9ce941ac73d55667d16bf11b2e0CAS | 11925399PubMed |

Meskhi, A., and Seif, M. W. (2006). Premature ovarian failure. Curr. Opin. Obstet. Gynecol. 18, 418–426.
Premature ovarian failure.Crossref | GoogleScholarGoogle Scholar | 16794423PubMed |

Nelson, L. M. (2009). Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 360, 606–614.
Clinical practice. Primary ovarian insufficiency.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFyhsr4%3D&md5=8e7c5fc6752fe7c0b0cb200804e3063cCAS | 19196677PubMed |

Nelson, L. M., Anasti, J. N., Kimzey, L. M., Defensor, R. A., Lipetz, K. J., White, B. J., Shawker, T. H., and Merino, M. J. (1994). Development of luteinized Graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J. Clin. Endocrinol. Metab. 79, 1470–1475.
| 1:CAS:528:DyaK2MXit1ekt7w%3D&md5=b062e2c1ede62452ec643edf180e9fa2CAS | 7962345PubMed |

Pedersen, T., and Peters, H. (1968). Proposal for a classification of oocytes and follicles in mouse ovary. J. Reprod. Fertil. 17, 555–557.
Proposal for a classification of oocytes and follicles in mouse ovary.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF1M7jsFSgtw%3D%3D&md5=045d79e8d62eed7d9a4f6ad5294e1fcaCAS | 5715685PubMed |

Philpott, C. C., Ringuette, M. J., and Dean, J. (1987). Oocyte-specific expression and developmental regulation of ZP3, the sperm receptor of the mouse zona pellucida. Dev. Biol. 121, 568–575.
Oocyte-specific expression and developmental regulation of ZP3, the sperm receptor of the mouse zona pellucida.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXitFWlu7Y%3D&md5=f250e9e4fa3df13d899f8a8b84eb5714CAS | 2884155PubMed |

Piomboni, P., Focarelli, R., Capaldo, A., Stendardi, A., Cappelli, V., Cianci, A., La Marca, A., Luddi, A., and De Leo, V. (2014). Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin. J. Assist. Reprod. Genet. 31, 1269–1276.
Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2M%2FgvVakuw%3D%3D&md5=68631c0dacf746d88a29591822a8a63bCAS | 25113619PubMed |

Qiao, J., and Feng, H. L. (2011). Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum. Reprod. Update 17, 17–33.
Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence.Crossref | GoogleScholarGoogle Scholar | 20639519PubMed |

Shelling, A. N. (2010). Premature ovarian failure. Reproduction 140, 633–641.
Premature ovarian failure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFCnsbfN&md5=cc78173bc984ddd4a8da7dcd66eaefc7CAS | 20716613PubMed |

Shi, S., Williams, S. A., Seppo, A., Kurniawan, H., Chen, W., Ye, Z., Marth, J. D., and Stanley, P. (2004). Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and hybrid N-glycans develop and implant. Mol. Cell. Biol. 24, 9920–9929.
Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and hybrid N-glycans develop and implant.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXpslOnurk%3D&md5=c21f5e3d4f742ea451c283673d5ff0b5CAS | 15509794PubMed |

Sinclair, A. M., and Elliott, S. (2005). Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins. J. Pharm. Sci. 94, 1626–1635.
Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXnvVWnurg%3D&md5=9371d792e22dfb10f900164e54af0cffCAS | 15959882PubMed |

Spears, N., Baker, S., Srsen, V., Lapping, R., Mullan, J., Nelson, R., and Allison, V. (2002). Mouse ovarian follicles secrete factors affecting the growth and development of like-sized ovarian follicles in vitro. Biol. Reprod. 67, 1726–1733.
Mouse ovarian follicles secrete factors affecting the growth and development of like-sized ovarian follicles in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XptVels7k%3D&md5=6110a2415464af1cec0c31ae8696e32aCAS | 12444046PubMed |

Suzuki, N., Yoshioka, N., Takae, S., Sugishita, Y., Tamura, M., Hashimoto, S., Morimoto, Y., and Kawamura, K. (2015). Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum. Reprod. 30, 608–615.
Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency.Crossref | GoogleScholarGoogle Scholar | 25567618PubMed |

West, E. R., Xu, M., Woodruff, T. K., and Shea, L. D. (2007). Physical properties of alginate hydrogels and their effects on in vitro follicle development. Biomaterials 28, 4439–4448.
Physical properties of alginate hydrogels and their effects on in vitro follicle development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXovFSqtr4%3D&md5=2cf325db84aaebef9f857c3bf247509fCAS | 17643486PubMed |

Williams, S. A., and Stanley, P. (2011). Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. Endocrinology 152, 1057–1066.
Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXktVGrsbk%3D&md5=2fde1e9f6fda3cbc487dc9287294c6deCAS | 21239444PubMed |

Williams, S. A., Xia, L., Cummings, R. D., McEver, R. P., and Stanley, P. (2007). Fertilization in mouse does not require terminal galactose or N-acetylglucosamine on the zona pellucida glycans. J. Cell Sci. 120, 1341–1349.
Fertilization in mouse does not require terminal galactose or N-acetylglucosamine on the zona pellucida glycans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlsFSjtL0%3D&md5=9a931193c6fb46998a3ecb0501982113CAS | 17374637PubMed |

Woodruff, T. K., and Shea, L. D. (2011). A new hypothesis regarding ovarian follicle development: ovarian rigidity as a regulator of selection and health. J. Assist. Reprod. Genet. 28, 3–6.
A new hypothesis regarding ovarian follicle development: ovarian rigidity as a regulator of selection and health.Crossref | GoogleScholarGoogle Scholar | 20872066PubMed |

Xu, M., West, E., Shea, L. D., and Woodruff, T. K. (2006). Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol. Reprod. 75, 916–923.
Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1yjtr7O&md5=676addc7fd39feae9b830c8d6704b50bCAS | 16957022PubMed |