Abstract
Purpose
Estrogens are known to selectively influence cell proliferation. Physiological variations of blood hormone concentration might play a role in regulating the level of X chromosome aneuploidy. In this study we observed the percentages of X aneuploid cells in standard lymphocyte cultures from blood samples obtained in relation to the menstrual cycle, noting whether collection occurred during either the follicular or the luteal phase.
Methods
A study consisting of 28 women with X mosaicism and recurrent pregnancy loss, and 28 age-matched healthy controls. Cytogenetic studies were carried out on peripheral blood samples according to standard procedures.
Results
A significant difference in the percentage of X aneuploidy was found in blood samples obtained during different phases of the menstrual cycle. In the case group, the mean value of aneuploid cells in the follicular and luteal phase samples was 10.0 and 6.3 % respectively and in the control group, it was 2.8 and 1.0 % (P < 0.0001). The difference in the case group varied between 0 and 8 % (3.6 ± 2.1 %) and in the control group between 0 and 4 % (1.7 ± 1.1 %). The specificity for detecting true X mosaicism was 0.875. We estimate that the initial diagnosis of X mosaicism could be correct in 68 % of patients with recurrent pregnancy loss.
Conclusions
This observational study establishes that the time of blood sampling in relation to the menstrual cycle can influence lymphocyte X chromosome mosaicism. The results, further proven by additional controlled studies, would have practical implications for genetic counselling and fertility treatment.
Similar content being viewed by others
References
Guttenbach M, Koschorz B, Bernthaler U, Grimm T, Schmid M. Sex chromosome loss and aging: in situ hybridization studies on human interphase nuclei. Am J Hum Genet. 1995;57:1143–50.
Wise JL, Crout RJ, McNeil DW, Weyant RJ, Marazita ML, Wenger SL. Cryptic subtelomeric rearrangements and X chromosome mosaicism: a study of 565 apparently normal individuals with fluorescent in situ hybridization. PLoS One. 2009;10:e5855.
Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res. 2007;116:181–5.
Morel F, Gallon F, Amice V, Le Bris MJ, Le Martelot MT, Roche S, et al. Sex chromosome mosaicism in couples undergoing intracytoplasmic sperm injection. Hum Reprod. 2002;17:2552–5.
Homer L, Le Martelot MT, Morel F, Amice V, Kerlan V, Collet M, et al. 45, X/46, XX mosaicism below 30 % of aneuploidy: clinical implications in adult women from a reproductive medical unit. Eu J Endocrinol. 2010;162:617–23.
Gersak K, Veble A. Low-level X chromosome mosaicism in women with sporadic premature ovarian failure. Reprod BioMed Online. 2011;22:399–403.
Peschka B, Laygraaf J, Van der Ven K, Montag M, Schartmann B, Schubert R, et al. Type and frequency of chromosome aberrations in 781 couples undergoing intra-cytoplasmic sperm injection. Hum Reprod. 1999;14:2257–63.
Wu RC, Kuo PL, Lin SJ, Liu CH, Tzeng C. X chromosome mosaicism in patients with recurrent abortion or premature ovarian failure. J Formos Med Assoc. 1993;92:953–6.
Devi AS, Metzger DA, Luciano AA, Benn PA. 45, X/46, XX mosaicism in patients with idiopathic premature ovarian failure. Fertil Steril. 1998;70:89–93.
Devi A, Benn PA. X-Chromosome abnormatities in women with premature ovarian failure. J Reprod Med. 1999;44:321–4.
Duzcan F, Atmaca M, Cetin GO, Bagci H. Cytogenetic studies in patients with reproductive failure. Acta Obstet Gynecol Scand. 2003;82:53–6.
Kuo PL, Guo HR. Mechanism of recurrent spontaneous abortions in women with mosaicism of X-chromosome aneuploidies. Fertil Steril. 2004;82:1594–601.
Wong MS, Lam ST. Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study. Hong Kong Med J. 2005;11:267–72.
Lakhal B, Braham R, Berguigua R, Bouali N, Zaouali M, Chaieb M, et al. Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients. Clin Genet. 2010;78:181–5.
Song Y, Chen Q, Zhang Z, Hou H, Zhang D, Shi Q. Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men. J Genet Genomics. 2009;36:467–74.
Tsuisui T, Suzuki N, Fukuda S, Sato M, Maizumi H, McLachlan JA, et al. 17beta-estradiol-induced cell transformation and aneuploidy of Syrian hamster embryo cells in culture. Carcinogenesis. 1987;8:1715–9.
Wheeler WJ, Cherry LM, Downs T, Hsu TC. Mitotic inhibition and aneuploidy induction by naturally occurring and synthetic estrogens in Chinese hamster cells in vitro. Mutat Res. 1986;171:31–41.
Horsman DE, Dill FJ, McGillivray BC, Kalousek DK. X chromosome aneuploidy in lymphocyte cultures from women with recurrent spontaneous abortion. Am J Med Genet. 1987;28:981–7.
Bakos O, Lundkvist O, Wide L, Bergh T. Ultrasonographical and hormonal description of the normal ovulatory menstrual cycle. Acta Obstet Gynecol Scand. 1994;73:790–6.
Gore MA, Nayudu PL, Vlaisavljevic V, Thomas N. Prediction of ovarian cycle outcome by follicular characteristics, stage 1. Hum Reprod. 1995;10:2313–9.
Clouston HJ. Lymphocyte culture. protocol 8. In: Rooney DE, editor. Human cytogenetics: constitutional analysis. Oxford: Oxford University Press; 2001. p. 45–6.
Hook EB. Exclusion of chromosomal mosaicism: table of 90, 95 and 99 % confidence limits and comments on use. Am J Hum Genet. 1977;29:94–7.
Hsu LY, Kaffe S, Jenkins EC, Alonso L, Benn PA, David K, et al. Proposed guidelines for diagnosis of chromosome mosaicism in amniocytes based on data derived from chromosome mosaicism and pseudomosaicism studies. Prenat Diagn. 1992;12:555–73.
R Development Core Team. R - A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing, 2011. http://www.R-project.org/. Accessed 12 April 2012.
Gardner RJM, Sutherland GR. Parental sex chromosome aneuploidy. In: Gardner RJM, Sutherland GR, editors. Chromosome abnormalities and genetic counseling. New York: Oxford University Press; 2003. p. 191–202.
Shaffer LG, Tommerup N. An international system for human cytogenetic nomenclature (cytogenetic and genome research). Basel: Karger; 2005.
van Dessel HJ, Schipper I, Pache TD, van Geldorp H, de Jong FH, Fauser BC. Normal human follicle development: an evaluation of correlations with oestradiol, androstenedione and progesterone levels in individual follicles. Clin Endocrinol. 1996;44:191–8.
Macklon NS, Fauser BCJM. Follicle-stimulating hormone and advanced follicle development in the human. Arch Med Res. 2001;32:595–600.
Quick EL, Parry EM, Parry JM. Do oestrogens induce chromosome specific aneuploidy in vitro, similar to the pattern of aneuploidy seen in breast cancer? Mutat Res. 2008;651:46–55.
Parry JM, Al-Obaidly A, Kayani M, Nabeel T, Strefford J, et al. Spontaneous and induced aneuploidy, considerations which may influence chromosome malsegregation. Mutat Res. 2002;504:119–29.
Lee S, Kim J, Jang B, Hur S, Jung U, Kil K, et al. Fluctuation of peripheral blood T, B, and NK cells during a menstrual cycle of normal healthy women. J Immunol. 2010;185:756–62.
Weinberg A, Enomoto L, Marcus R, Canniff J. Effect of menstrual cycle variation in female sex hormones on cellular immunity and regulation. J Reprod Immunol. 2011;89:70–7.
Acknowledgments
The authors would like to thank the laboratory and clinical staff of the Institute of Medical Genetics (University Medical Center Ljubljana, Slovenia) for their excellent technical assistance. The study was supported by a grant from the Ministry of Higher Education, Science and Technology of the Republic of Slovenia (No. P3―0124).
Conflict of interest
The authors declare no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Capsule In women with X mosaicism and recurrent pregnancy loss a significant difference in the percentage of X aneuploidy was found between follicular- and luteal-phase blood samples.
Rights and permissions
About this article
Cite this article
Gersak, K., Perme-Pohar, M., Veble, A. et al. Possible influence of menstrual cycle on lymphocyte X chromosome mosaicism. J Assist Reprod Genet 32, 111–116 (2015). https://doi.org/10.1007/s10815-014-0377-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-014-0377-y