Telomere Length in Idiopathic Recurrent Pregnancy Loss

Onat, Taylan; Çaltekin, Melike Demir; Başer, Emre; Kırmızı, Demet Aydoğan; Kara, Mustafa; Ercan, Fedi

doi:10.1055/a-1345-9821

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…Our findings that a shortened TL was correlated with an increased risk of SA were consistent with those of prior research. For instance, a recent case-control study found that women with iRPL (n=40) had significantly shorter peripheral blood leukocyte TL in early follicular stages than healthy women (n=41) with a comparable age and body mass index (P=0.006) (43). In studies of infertile women undergoing in vitro fertilization (IVF), shorter peripheral blood leukocyte TL was linked with a higher incidence of embryonic aneuploidy, a major contributor to pregnancy loss (P=0.01) (44).…”

Section: Discussionmentioning

confidence: 99%

Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes

Han

Liu

2023

Front. Endocrinol.

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BackgroundNumerous observational studies have revealed a correlation between telomere length (TL) and adverse pregnancy outcomes (APOs). However, the impacts of TL on APOs are still unclear.MethodsMendelian randomization (MR) was carried out using summary data from genome-wide association studies (GWAS). Inverse variance weighted (IVW) was employed as the primary analysis to explore the causal relationship between TL and APOs. The exposure data came from a GWAS dataset of IEU analysis of the United Kingdom Biobank phenotypes consisting of 472,174 European participants. Summary-level data for five APOs were obtained from the GWAS datasets of the FinnGen consortium. We also performed multivariate MR (MVMR), adjusting for smoking, alcohol intake, body mass index (BMI), and number of live births. In addition, we conducted a series of rigorous analyses to further examine the validity of our MR findings.ResultsAfter Bonferroni correction and rigorous quality control, univariable MR (UVMR) demonstrated that a shorter TL was significantly associated with an increased risk of spontaneous abortion (SA) (odds ratio [OR]: 0.815; 95% confidence interval [CI]: 0.714–0.930; P = 0.002) and preterm birth (PTB) (OR: 0.758; 95% CI: 0.632-0.908; P = 0.003) in the IVW model. There was a nominally significant relationship between TL and preeclampsia (PE) in the IVW model (OR: 0.799; 95% CI: 0.651-0.979; P = 0.031). However, no significant association was found between TL and gestational diabetes mellitus (GDM) (OR: 0.950; 95% CI: 0.804-1.122; P = 0.543) or fetal growth restriction (FGR) (OR: 1.187; 95% CI: 0.901-1.565; P = 0.223) among the five statistical models. Furthermore, we did not find a significant causal effect of APOs on TL in the reverse MR analysis. MVMR analysis showed that the causal effects of TL on SA remained significant after accounting for smoking, alcohol intake, BMI, and number of live births.ConclusionOur MR study provides robust evidence that shorter telomeres were associated with an increased risk of SA. Further work is necessary to investigate the potential mechanisms. UVMR and MVMR findings showed limited evidence that TL affects the risk of PTB, PE, GDM, and FGR, illustrating that the outcomes of previous observational studies may have been confounded.

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Section: Discussionmentioning

confidence: 99%

Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes

Han

Liu

2023

Front. Endocrinol.

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“…Strikingly, in tubal pregnancies, which are a type of ectopic implantation caused by zygotes fixed outside the uterine cavity [79], the telomere length of placenta samples was similar to controls [80 ▪ ]. Finally, LTL was found to be shorter in women with idiopathic recurrent pregnancy loss [81].…”

Section: Uterine Aging and Implantationmentioning

confidence: 99%

Telomeres, aging and reproduction

Córdova-Oriz

Chico-Sordo

Varela

2022

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewWomen's fertility decay starts at the mid 30 s. However, the current delay of childbearing leads to ovarian aging and the need of assisted reproduction technologies (ART). Telomere biology is one of the main pathways involved in organismal aging. Thus, this review will focus on the knowledge acquired during the last 2 years about the telomere pathway and its influence on female fertility and the consequences for the newborn.Recent findingsNew research on telomere biology reaffirms the relationship of telomere attrition and female infertility. Shorter maternal telomeres, which could be aggravated by external factors, underly premature ovarian aging and other complications including preeclampsia, preterm birth and idiopathic pregnancy loss. Finally, the telomere length of the fetus or the newborn is also affected by external factors, such as stress and nutrition.SummaryRecent evidence shows that telomeres are implicated in most processes related to female fertility, embryo development and the newborn's health. Thus, telomere length and telomerase activity may be good biomarkers for early detection of ovarian and pregnancy failures, opening the possibility to use telomere therapies to try to solve the infertility situation.

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Cellular senescence in reproduction: a two-edged sword

Pretto,

Nabinger,

Filippi-Chiela

et al. 2024

Biology of Reproduction

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Cellular senescence (CS) is the state when cells are no longer capable to divide even after stimulation with grown factors. Cells that begin to undergo CS stop in the cell cycle and enter a suspended state without committing to programmed cell death. These cells assume a specific phenotype and influence their microenvironment by secreting molecules and extracellular vesicles that are part of the so-called senescent cell–associated secretory phenotype (SASP). Cellular senescence is intertwined with physiological and pathological conditions in the human organism. In terms of reproduction, senescent cells are present from reproductive tissues and germ cells to gestational tissues, and participate from fertilization to delivery, going through adverse reproductive outcomes such as pregnancy losses. Furthermore, various SASP molecules are enriched in gestational tissues throughout pregnancy. Thus, the aim of this review is to provide a basis about the features and potential roles played by CS throughout the reproductive process, encompassing its implication in each step of it and proposing a way to manage it in adverse reproductive contexts.

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Telomere Length in Idiopathic Recurrent Pregnancy Loss

Cited by 3 publications

References 38 publications

Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes

Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes

Telomeres, aging and reproduction

Cellular senescence in reproduction: a two-edged sword

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