Comparative Cytogenetic Analysis of Spontaneous Abortions in Recurrent and Sporadic Pregnancy Losses

Nikitina, Tatiana; Саженова, Е. А.; Tolmacheva, E. N.; Суханова, Н. Н.; Skryabin, N. A.; Vasilyev, S. A.; Nemtseva, T. N.; Yuriev, S. Yu.; Lebedev, I. N.

doi:10.1159/000446099

Cited by 35 publications

(44 citation statements)

References 41 publications

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“…In contrast, reports of aneuploidy associated with pregnancy loss in domesticated animals is rarely reported, and never in the horse. Here we identified autosomal aneuploidies in 20% of naturally occurring equine EPL conceptuses, slightly lower than the 35-50% reported in women [20, 45] possibly explained by the shorter gestational time frame used in our study. Seven of the aneuploidy types we described were unique to the study, including two monosomies.…”

Section: Discussioncontrasting

confidence: 78%

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Shilton

Kahler

Davis

et al. 2020

Preprint

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Chromosome abnormalities are well documented in human spontaneous abortion studies, yet rarely reported in domesticated animals. Rodent models have previously been used to study the effects of maternal ageing on oocyte quality and ultimately aneuploidy, however the differing endocrine profiles, oocyte characteristics and the polytocous nature of rodents are limitations for translation into human medicine. Early Pregnancy Loss (EPL) occurs in 5-10% of confirmed equine pregnancies and has no diagnosis in over 80% of cases. Aneuploidy has never been described in equine pregnancy loss, thus the objectives of this study were to quantify the frequency and characteristics of aneuploidy associated with equine EPL. EPL conceptuses were submitted from clinical cases of spontaneous pregnancy loss (14-65 days of gestation) between 2013 and 2018. Age matched control conceptuses were obtained from terminated clinically normal pregnancies (CNP). Aneuploidy was detected in 12/55 EPLs (21.8%), 0/10 CNP, 0/5 healthy term chorioallantois, and 0/5 healthy adult mares via genotyping. Whole genome sequencing (30X) and ddPCR validated results. Aneuploidies involved 10/32 equine chromosomes, consisting of nine trisomies and three monosomies. Autosomal aneuploidies were detected in both placental and fetal compartments in all samples tested. Aneuploid types (7/9) were mostly unique to EPL, supporting their embryonic/fetal lethality. Presenting the first evidence of aneuploidies in failed equine pregnancies not only provides the initial step in identifying genetic causes for these early losses, but also offers the horse as a new model for studying naturally occurring aneuploidy. We also demonstrate that SNP arrays provide a simple, cost effective way to screen aneuploidies across a large population.Author SummaryThe first 8 weeks of pregnancy is a critical time in both humans and horses, as the majority of pregnancy losses occur during this period. Despite such high prevalence, many cases do not have a known cause. Abnormal chromosome number (aneuploidy) is the most common finding in human pregnancy loss studies, but to date no equivalent study has been performed in domesticated animals, including the horse. We studied the genetics of naturally occurring pregnancy losses from Thoroughbred horses and found a similar level of aneuploidy to that observed in women. As humans and horses share similarities in their reproductive biology (ageing eggs, increased pregnancy loss in older mothers, similar key hormones), we suggest that by comparing the genetics of these two species, greater advances in identifying causes of aneuploidy pregnancy can be reached. Thoroughbred horses also tend to be more inbred than humans, facilitating the identification of mutations that increase the chance of aneuploidy, and this knowledge could potentially be applied in human medicine, as well as in species conservation.

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Section: Discussioncontrasting

confidence: 78%

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Shilton

Kahler

Davis

et al. 2020

Preprint

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“…However, conflicting results have been reported. Nikitina et al (20) reported that the frequency of abortions with normal karyotypes was significantly higher in maternal patients with recurrent miscarriages as compared to that in patients with SM (53. (24) and Grande et al (25) reported conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Association between fetal chromosomal abnormalities and the frequency of spontaneous abortions

Yang

Tao²,

Zhao

et al. 2020

Exp Ther Med

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Fetal chromosomal abnormalities are a common cause of spontaneous abortion. The present study investigated the association between fetal chromosomal abnormalities and the frequency of spontaneous abortions to enable clinicians to provide more informed genetic counseling. A total of 182 patients with a history of spontaneous abortions were recruited from July 2015 to August 2017. G-banding cytogenetic analysis and novel high-throughput ligation-dependent probe amplification (HLPA) techniques were performed on conception in all 182 patients to detect chromosomal abnormalities. Low-coverage whole-genome sequencing (WGS) was performed in 74 patients to detect copy number variations (CNVs). There were no significant differences in the incidence of karyotype abnormalities between patients with sporadic miscarriages (48.0%; SM group) and patients suffering recurrent spontaneous abortions (44.8%; RSA group). The maternal age was markedly higher in patients with 3 miscarriages. WGS indicated that the incidence of pathogenic CNVs in the RSA group was higher than that in the SM group, but the difference was not significant. In conclusion, a high incidence of karyotype abnormalities and pathogenic CNVs was observed in patients with spontaneous abortion. However, no association between fetal chromosomal abnormalities and the number of spontaneous abortions was observed. HLPA assays may be used as an alternative method for fetal karyotype analysis and determination of CNVs in patients with SM and RSA.

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“…Numerical chromosome anomalies are the most common cause of spontaneous abortion, but this is not the case for repeated miscarriages. As the number of miscarriages increases, the probability of further spontaneous abortions with normal karyotype and the probability to lose the next pregnancy increase as well [Nikitina et al, 2016]. However, if one member of the couple is a carrier of structural chromosome abnormalities (balanced transloca- tions, inversions, marker chromosomes, etc.…”

Section: Discussionmentioning

confidence: 99%

A Familial Small Supernumerary Marker Chromosome 15 Associated with Cryptic Mosaicism with Two Different Additional Marker Chromosomes Derived de novo from Chromosome 9: Detailed Case Study and Implications for Recurrent Pregnancy Loss

Čulić¹,

Lasan-Trčić²,

Liehr

et al. 2018

Cytogenet Genome Res

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We report a case of familial small supernumerary marker chromosome 15 in a phenotypically normal female with 4 recurrent spontaneous abortions and a healthy child. The initial karyotype showed a small, bisatellited, apparently metacentric marker chromosome, 47,XX,+idic(15)(q11.1), maternally inherited. The proband's mother was mosaic for the idic(15)(q11.1) without pregnancy loss. Reexamination of the proband's karyotype revealed cryptic mosaicism for 1 ring and 1 minute chromosome derived de novo from chromosome 9 in 2% of the metaphases. In FISH analysis, the patient's karyotype was mos 47,XX,+idic(15)(q11.1)mat[100]/49,XX,+idic(15)(q11.1)mat,+r(9;9;9;9),+der(9)dn[2]. The second spontaneous abortion had trisomy 9 (47,XX,+9); the third had mosaic trisomy 9 in 21% of the nuclei and isodicentric chromosome 15 in 36% of the nuclei (mos 48,XN,+9,+idic(15)(q11.1)/47,XN,+9/47,XN,+idic(15)(q11.1)/46,XN). The first and fourth abortions were not cytogenetically studied. The cause of the spontaneous abortions in this patient is likely the cryptic mosaicism for ring and minute chromosomes 9, and gonadal mosaicism is most probable, due to the 2 abortions.

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Comparative Cytogenetic Analysis of Spontaneous Abortions in Recurrent and Sporadic Pregnancy Losses

Cited by 35 publications

References 41 publications

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Association between fetal chromosomal abnormalities and the frequency of spontaneous abortions

A Familial Small Supernumerary Marker Chromosome 15 Associated with Cryptic Mosaicism with Two Different Additional Marker Chromosomes Derived de novo from Chromosome 9: Detailed Case Study and Implications for Recurrent Pregnancy Loss

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