Assisted Reproduction · Safety and Risks
RRM Academy Synopsis
Telomeres in human eggs and embryos change as they develop
Telomeres change in length as human eggs mature and embryos grow, a 2023 narrative review reports. Telomeres are protective caps on chromosome ends. To the authors' knowledge, no study has tested whether ovarian stimulation changes them in human eggs or embryos. Culture findings come from mouse and hamster embryos, and freezing findings from ovarian tissue and retinal cells.
Key Findings
- Immature human oocytes had longer telomeres (11.41 ± 0.81 kb) than mature oocytes (8.79 ± 0.86 kb) in one study using a fluorescent labeling method.
- Cleavage-stage embryos had telomeres of 8.43 kb and blastocysts 12.22 kb. Telomerase activity climbed from the morula stage to blastocysts.
- Sister oocytes from women who became pregnant had longer telomeres (7.5 ± 1.17 kb) than those from women who had no pregnancy (6.2 ± 1.69 kb).
- A mouse study found that in vitro culture left blastocyst telomere length unchanged, while a longer culture (120 h versus 96 h) of IVF-derived blastocysts lengthened it.
- Ovarian tissue from women, frozen by the slow-freezing method and thawed, mostly had shorter telomeres (8.34 ± 1.83 kb) than fresh tissue (9.57 ± 1.47 kb).
Interpretation
The paper is a narrative review of published studies. A limited number of studies have measured telomeres in human eggs and embryos. Several mechanism claims rest on mouse, hamster or rat cells. Studies of telomere length as a marker of egg quality disagree: one group linked it to pregnancy, while another concluded it is unreliable for predicting pregnancy outcomes. Proposed effects of ART steps on telomeres are hypotheses resting on oxidative stress and DNA methylation.
RRM Context
Restorative reproductive medicine asks why eggs and embryos struggle, including age and oxidative stress. The review ties telomere shortening to both and lists no human data on ovarian stimulation and egg telomeres. IVF proceeds without establishing why conception fails, so what its laboratory steps do to eggs remains open. The authors add that an egg cannot be measured and then used for fertilization.
Abstract
Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.