Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita
- 13 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Assisted Reproduction and Genetics
- Vol. 37 (5), 1221-1225
- https://doi.org/10.1007/s10815-020-01758-x
Abstract
Purpose To determine the impact of accelerated telomere shortening on the fertility parameters and treatment outcomes of a woman with dyskeratosis congenita (DKC). Methods A case study of the clinical data, blood, discarded oocytes, and arrested embryos of a woman with DKC and donated cryopreserved embryos from unaffected patients. Mean telomere length in blood cells was analyzed by flow cytometry–fluorescence in situ hybridization (flow-FISH) and qPCR. The load of short telomeres in blood cells was measured by universal single telomere length analysis (Universal STELA). The mean telomere length in embryos was analyzed by single-cell amplification of telomere repeats (SCATR) PCR. Results Comparison of clinical parameters revealed that the DKC patient had reduced anti-Mullerian hormone (0.3 vs 4.1 ± 5.7 ng/ML), reduced oocytes retrieved (7 vs 18.5 ± 9.5), reduced fertilization rate, and reduced euploidy rate relative to unaffected patients. Additionally, mean telomere length in DKC embryos were shorter than unaffected embryos. However, hormone treatment led to increased leukocyte telomere length, while the load of short telomeres was also shown to decrease during the course of treatment. Conclusions We demonstrate for the first time the direct detrimental impacts of short telomeres on female fertility. We further demonstrate positive effects of hormone treatments for people with telomere disorders.Keywords
Funding Information
- Stanley H. Kaplan Research Fund
This publication has 25 references indexed in Scilit:
- Robust measurement of telomere length in single cellsProceedings of the National Academy of Sciences of the United States of America, 2013
- Telomere DNA Deficiency Is Associated with Development of Human Embryonic AneuploidyPLoS Genetics, 2011
- Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cellsNature, 2011
- The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cellsAging Cell, 2010
- Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patientsNature, 2010
- Short telomeres are preferentially elongated by telomerase in human cellsFEBS Letters, 2009
- Telomere lengthening early in developmentNature, 2007
- Telomeres and telomerase: their mechanisms of action and the effects of altering their functionsFEBS Letters, 2004
- Nuclear Origin of Aging-Associated Meiotic Defects in Senescence-Accelerated Mice1Biology of Reproduction, 2004
- Telomeres in dyskeratosis congenita.Nature Genetics, 2004