Advanced mare age impairs the ability of in vitro‐matured oocytes to correctly align chromosomes on the metaphase plate

Rizzo, Maria; Ducheyne, Kaatje; Deelen, C.; Beitsma, M.; Cristarella, Santo; Quartuccio, Marco; Stout, T. A. E.; Ruijter-Villani, Marta de

doi:10.1111/evj.12995

Cited by 31 publications

(54 citation statements)

References 26 publications

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“…Multivariable analysis has found the mare level factors of increasing age, one previous live foal and the presence of uterine cysts to be positively associated with EPL. Evidence suggests it is oocyte deficits rather than endometrial dysfunction which are the main contributors relating mare age to EPL [20,21,26,27]. Cytogenetic analysis to establish chromosomal aberrations would be beneficial to explore the pathophysiology behind oocyte-related failures.…”

Section: Resultsmentioning

confidence: 99%

“…The contribution of chromosomal abnormalities to EPL in the mare is not currently known, although two chromosomal abnormalities have been demonstrated experimentally in equine embryos [24] and new methods to study conceptual material from clinically failed pregnancies are now available [25]. It is also plausible that EPL derived from oocyte defects could arise by mitochondrial defects or chromosome misalignment on the metaphase II spindle which have been shown to increase in aged mares [26,27]. These oocyte abnormalities are likely to also contribute to earlier pregnancy losses (prior to day 15) not assessed as part of this study.…”

Section: Discussionmentioning

confidence: 99%

“…A 2011 study of 1476 Japanese thoroughbreds did use multivariable analysis to investigate factors associated with losses up to day 35 of pregnancy [2]. They found foal heat mating and the presence of uterine cysts to contribute to the incidence of EPL (defined as loss from gestational day [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. This study did not, however, assess the impact of therapeutic agents, stallions or twin pregnancies on pregnancy outcome.…”

Section: Introductionmentioning

confidence: 99%

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Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares

et al. 2019

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares

et al. 2019

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“…Aged oocytes also display altered microtubule spindle alignment [57] and weakened centromere cohesion [58] resulting in increased risk of aneuploidy. In the mare, advancing maternal age significantly increases the risk of chromosome misalignment [19] and early pregnancy loss [7]. Therefore we proposed that advancing mare age would increase the risk of aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

“…Whilst an abnormal uterine environment, more prevalent in aged mares, is likely to be a contributing factor, experiments involving the transfer of embryos from young mares into old mares (and vice versa) have suggested that this is not the main age-related underlying cause [16]. Oocytes from aged mares are of lower quality compared with younger fertile mares [17–19], indicating oocyte quality as a more likely risk factor for pregnancy loss.…”

Section: Introductionmentioning

confidence: 99%

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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Placentation in Equids

Antczak

Allen

2021

Advances in Anatomy, Embryology and Cell Biology

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Advanced mare age impairs the ability of in vitro‐matured oocytes to correctly align chromosomes on the metaphase plate

Cited by 31 publications

References 26 publications

Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares

Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares

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

Placentation in Equids

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