Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Chromosomal Analysis of Cumulus Cells as a Future Predictor for Oocyte Aneuploidy: A Case Report

Authors
1 Department of Embryology, The Centre for Reproductive and Genetic Health, London, UK; Institute for Women’s Health, University College London, London, UK
2 Department of Embryology, The Centre for Reproductive and Genetic Health, London, UK
3 Institute for Women’s Health, University College London, London, UK
4 School of Medicine, Cardiff University, Cardiff, UK
Abstract
Background: Within the ovary, the optimal growth of the follicle, oocyte maturation and ovulation are highly conditioned by the two-way cross talk and interactions between the oocyte and the immediate somatic cells, known as cumulus cells (CCs). This biological communication between cell lines triggered the interest in the study of CCs as a biomarker of oocyte competence. Case Presentation: The findings of a 45,X mosaic pattern on CCs from a female patient with unremarkable medical history are reported in this study. The patient came to the Centre for Reproductive and Genetic Health, London on 14th August 2019 for her first visit and the follow up procedures were done for her to determine underlying genetic status. For this purpose, four sources of DNA including CCs, blood lymphocytes, buccal cells and immature oocytes were analyzed in the present report. Conclusion: In the present case study, the hypothesis of the female patient being mosaic 45,X was confirmed although the degree of mosaicism and whether this was affecting the germinal line could not be determined. In the event of the discovery of a cell line with an apparently abnormal genetic makeup, genetic counselling is important in order to understand the implications from somatic to germinal cells for patients exploring fertility journeys.
Keywords

  1. Son WY, Das M, Shalom-Paz E, Holzer H. Mechanisms of follicle selection and development. Minerva Ginecol. 2011;63(2):89-102.
  2. Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V, et al. A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 2008;14(12):711-9.
  3. Feuerstein P, Puard V, Chevalier C, Teusan R, Cadoret V, Guerif F, et al. Genomic assessment of human cumulus cell marker genes as predictors of oocyte developmental competence: impact of various experimental factors. PLoS One. 2012;7(7):e40449.
  4. Fragouli E, Wells D, Iager AE, Kayisli UA, Patrizio P. Alteration of gene expression in human cumulus cells as a potential indicator of oocyte aneuploidy. Hum Reprod. 2012;27(8):2559-68.
  5. Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res. 2007;116(3):181-5.
  6. Sugawara N, Kimura Y, Araki Y. Case report: a successful pregnancy outcome in a patient with non-mosaic Turner syndrome (45, X) via in vitro fertilization. Hum Cell. 2013;26(1):41-3.
  7. Peek R, Schleedoorn M, Smeets D, van de Zande G, Groenman F, Braat D, et al. Ovarian follicles of young patients with Turner’s syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod. 2019;34(9):1686-96.
  8. Gilbert SF. Developmental Biology. 6th ed. Sunderland (MA): Sinauer Associates; 2000.
  9. Peek R, Schleedoorn M, Smeets D, van de Zande G, Groenman F, Braat D, et al. Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod. 2019;34(9):1686-96.
  10. Turner JMA. Meiotic silencing in mammals. Annu Rev Genet. 2015;49:395-412.
  11. Machiela MJ, Zhou W, Karlins E, Sampson JN, Freedman ND, Yang Q, et al. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat Commun. 2016;7:11843.
  12. Hook EB. Exclusion of chromosomal mosaicism: tables of 90%, 95% and 99% confidence limits and comments on use. Am J Hum Genet. 1977;29(1):94-7.
  13. Deng X, Berletch JB, Nguyen DK, Disteche CM. X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet. 2014;15(6):367-78.
  14. Aller V, Gargallo M, Abrisqueta JA. Familial transmission of a duplication-deficiency X chromosome associated with partial Turner syndrome. Clin Genet. 1995;48(6):317-20.
  15. Held KR, Kerber S, Kaminsky E, Singh S, Goetz P, Seemanova E, et al. Mosaicism in 45,X Turner syndrome: does survival in early pregnancy depend on the presence of two sex chromosomes? Hum Genet. 1992;8(3):288-94.
  16. Varela M, Shapira E, Hyman DB. Ullrich-Turner syndrome in mother and daughter: prenatal diagnosis of a 46,X,del(X)(p21) offspring from a 45,X mother with low-level mosaicism for the del(X)(p21) in one ovary. Am J Med Genet. 1991;39(4):411-2.
  17. Goldman RH, Racowsky C, Farland LV, Munné S, Ribustello L, Fox JH. Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients. Hum Reprod. 2017;32(4):853-9.
  18. Cil AP, Bang H, Oktay K. Age-specific probability of live birth with oocyte cryopreservation: an individual patient data meta-analysis. Fertil Steril. 2013;100(2):492-9.e3.
  19. Verpoest W, Staessen C, Bossuyt PM, Goossens V, Altarescu G, Bonduelle M, et al. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial. Hum Reprod. 2018;33(9):1767-76.