Karyotype evaluation of repeated abortions in primary and secondary recurrent pregnancy loss

Nikitina, Tatiana; Саженова, Е. А.; Жигалина, Д. И.; Tolmacheva, E. N.; Суханова, Н. Н.; Lebedev, I. N.

doi:10.1007/s10815-020-01703-y

Cited by 22 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, upregulated miR‐149‐3p was found in melanoma patients, and miR‐149‐3p was of significance in the diagnosis of early‐stage melanoma 29 . A recent study highlighted that the possibility of having the identical karyotype pattern (recurrent normal or recurrent abnormal) in previous and subsequent abortion is elevated compared with chance 30 . Our further investigation revealed that miR‐149 expression exhibited no significant difference between RM patients with normal or abnormal karyotype, indicating that miR‐149 may not be responsible for RM due to chromosomal abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway

Wang

Chen

Chang

et al. 2020

J of Obstet and Gynaecol

View full text Add to dashboard Cite

Aim: Recently, microRNA-149 (miR-149) has been indicated to act as an oncogene or a tumor suppressor in various malignant tumors, while its inner mechanisms in recurrent miscarriage (RM) are still in infancy. Therein, this study intends to decode the mechanism of miR-149 in RM. Methods: miR-149 and RUNX2 expression in the chorionic tissues of normal pregnant women and RM patients were first examined, and the correlation between miR-149 and RUNX2 was analyzed. Subsequently, miR-149 was upregulated in HTR-8 cells or downregulated in BEWO cells, and then the changes in biological functions of trophoblasts in RM were detected. Furthermore, the expression of PTEN/Akt signaling pathway-related factors in trophoblasts was detected by western blot analysis. Results: miR-149 expression was increased while RUNX2 expression was suppressed in RM patients, and miR-149 was negatively correlated with RUNX2. Overexpressed miR-149 induced cell apoptosis and inhibited cell activity, while reduced miR-149 in trophoblasts contributed to opposite experimental results. Moreover, miR-149 promoted the expression of PTEN and inhibited Akt phosphorylation by targeting RUNX2, thereby inhibiting trophoblast activity and promoting their apoptosis. Conclusion: Our study demonstrates that miR-149 knockdown halted the RM development through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway

Wang

Chen

Chang

et al. 2020

J of Obstet and Gynaecol

View full text Add to dashboard Cite

show abstract

“…Aneuploidies occur in approximately 50% of spontaneous abortions during the first trimester of pregnancy. Abnormal karyotypes are distributed in the following order: single autosomal trisomy (40.5%), triploidy (approximately 15%), and X monosomy (7.5%) [29]. In spontaneous abortions, trisomy has been observed on all chromosomes, but trisomy on chromosomes 2, 13, 15 16, 18, 21, and 22 is the most frequent [28].…”

Section: Incidence Of Aneuploidy In Ontogenesismentioning

confidence: 99%

“…Only three differentially methylated CpG sites (DMS) were identified [111]. Despite this, embryos with trisomy 21 die very often at this stage of development [29].…”

Section: Influence Of Aneuploidy On Certain Chromosomes On the Level mentioning

confidence: 99%

Aneuploidy and DNA Methylation as Mirrored Features of Early Human Embryo Development

Tolmacheva

Vasilyev

Lebedev

2020

Genes

Self Cite

View full text Add to dashboard Cite

Genome stability is an integral feature of all living organisms. Aneuploidy is the most common cause of fetal death in humans. The timing of bursts in increased aneuploidy frequency coincides with the waves of global epigenetic reprogramming in mammals. During gametogenesis and early embryogenesis, parental genomes undergo two waves of DNA methylation reprogramming. Failure of these processes can critically affect genome stability, including chromosome segregation during cell division. Abnormal methylation due to errors in the reprogramming process can potentially lead to aneuploidy. On the other hand, the presence of an entire additional chromosome, or chromosome loss, can affect the global genome methylation level. The associations of these two phenomena are well studied in the context of carcinogenesis, but here, we consider the relationship of DNA methylation and aneuploidy in early human and mammalian ontogenesis. In this review, we link these two phenomena and highlight the critical ontogenesis periods and genome regions that play a significant role in human reproduction and in the formation of pathological phenotypes in newborns with chromosomal aneuploidy.

show abstract

“…Second, among women with repeat losses, the increased risk of a second chromosomally normal loss is modest 10 . Recent studies suggest a higher recurrence risk for chromosomally normal loss, but do not adjust for maternal age 11,12 . The increased recurrence risk for chromosomally normal loss is detectable among women <35, but not among older women because of the increasing risk of trisomy with age 13 .…”

Section: Introductionmentioning

confidence: 99%

Embryonic lethal genetic variants and chromosomally normal pregnancy loss

Kline¹,

Vardarajan

Avabhyankar

et al. 2020

Preprint

View full text Add to dashboard Cite

STUDY QUESTION: Are rare genetic variants in the conceptus associated with chromosomally normal pregnancy loss? SUMMARY ANSWER: The proportion of probands with at least one rare variant is increased in chromosomally normal loss conceptuses compared with controls (odds ratio 2.0, 95% CI 0.9, 3.0). WHAT IS ALREADY KNOWN: Among non-consanguineous families, one study of seven chromosomally normal losses to four couples with recurrent pregnancy loss (RPL) and a case report of a family with RPL of which one was known to be chromosomally normal identify compound heterozygote variants in three different genes as possibly causal. Among consanguineous families, RPL of chromosomally normal pregnancies with non-immune hydrops fetalis (NIHF) has been attributed to recessive variants in genes previously implicated for NIHF and new candidate genes. STUDY DESIGN, SIZE, DURATION: The starting sample was 52 chromosomally normal losses to 50 women, identified in 2003-2005 as part of a cohort study on trisomy and ovarian aging. The analytic sample comprises 19 conceptus-parent trios with DNA from 17 biologic parents (cases). The control group derives from the National Institutes of Mental Health's National Database for Autism Research (NDAR). It comprises 547 trios of unaffected siblings of autism cases and their parents. PARTICIPANTS/MATERIALS, SETTING, METHODS: We use exome sequencing to identify rare variants in the coding region of the genome. We defined variant rarity in two ways: ultra-rare (absent in gnomAD) and rare (heterozygote <10-3 in gnomAD) and, for autosomal recessive variants, absence of a homozygote in genomAD. We compare the rates of rare damaging variants (loss of function and missense - damaging) and the proportions of probands with at least one such variant in cases versus controls. Secondarily, 1) we repeat the analysis limiting it to variants in genes considered causal in fetal anomalies and 2) we compare the proportions of cases and controls with damaging variants in genes which we classified as possibly embryonic lethal based on a review which was blinded to case-control status. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of ultra-rare damaging variants (all de novo) are 0.21 and 0.17 in case and control probands, respectively. The corresponding rates for rare potentially pathogenic de novo variants are 0.37 and 0.24, respectively; for autosomal recessive variants they 0.11 and 0.03. The proportions of probands with at least one rare potentially damaging variant were 36.8% among cases and 22.9% among controls (odds ratio (OR) = 2.0, 95% CI 0.9, 3.0). Secondary analyses show no damaging variants in fetal anomaly genes among case probands; the proportion with variants in possible embryonic lethal genes was increased in case probands (OR=12.3, 95% CI 3.4, 61.1). Our data suggest that damaging variants in genes BAZ1A, FBN2 and TIMP2 may be lethal to the embryo. LIMITATIONS, REASONS FOR CAUTION: The number of case trios (n=19) limits the precision of our point estimates. We observe a moderate association between rare damaging variants and chromosomally normal loss with a confidence interval that includes unity. A larger sample is needed to estimate the magnitude of the association with precision and to identify the relevant biological pathways. WIDER IMPLICATIONS OF THE FINDINGS: Our data add to a very small literature on this topic. They suggest rare genetic variants in the conceptus may be a cause of chromosomally normal loss.

show abstract

Karyotype evaluation of repeated abortions in primary and secondary recurrent pregnancy loss

Cited by 22 publications

References 43 publications

Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway

Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway

Aneuploidy and DNA Methylation as Mirrored Features of Early Human Embryo Development

Embryonic lethal genetic variants and chromosomally normal pregnancy loss

Contact Info

Product

Resources

About