Cytogenetic analyses of human oocytes provide new data on non-disjunction mechanisms and the origin of trisomy 16

Garcia-Cruz, Raquel; Casanovas, A; Brieño‐Enríquez, Miguel A.; Robles, Pedro; Roig, Ignasi; Pujol, Aïda; Cabero, L.; Durbán, Mercé; Caldés, Montserrat Garcia

doi:10.1093/humrep/dep347

Cited by 29 publications

(16 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3E). In support of the idea that chiasmata become prematurely resolved in human oocytes, studies on chromosome 16 indicate that the incidence of unpaired homologs in fully grown MI oocytes is more than double that observed in fetal oocytes (Garcia-Cruz et al 2010b).…”

Section: Toward a Mechanistic Framework For Understanding The Maternamentioning

confidence: 92%

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Herbert

Kalleas

Cooney

et al. 2015

Cold Spring Harb Perspect Biol

186

175

View full text Add to dashboard Cite

In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond 35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms.

show abstract

Section: Toward a Mechanistic Framework For Understanding The Maternamentioning

confidence: 92%

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Herbert

Kalleas

Cooney

et al. 2015

Cold Spring Harb Perspect Biol

186

175

View full text Add to dashboard Cite

show abstract

“…On the other hand, the detection of spermatocytes II with separated sister chromatids provides the first evidence that balanced PSSC (or balanced pre-division), described in fresh oocytes II (Sandalinas et al, 2002;Garcia-Cruz et al, 2010), also occurs in human male meiosis. Separated sister chromatids may be at risk of improper segregation at anaphase II, leading to aneuploid spermatozoa.…”

Section: Origin Of Disomy and Diploidy In Human Spermatocytesmentioning

confidence: 95%

Meiotic non-disjunction mechanisms in human fertile males

Uroz

Templado

2012

Human Reproduction

View full text Add to dashboard Cite

background: In humans, little is known about the mechanisms of non-disjunction working in male meiosis, although considerable attention has been given to these mechanisms in female meiosis. The present study explores the origin of meiotic non-disjunction during human spermatogenesis and the chromosomes most commonly involved in this process. methods:We used Multiplex fluorescence in situ hybridization to carry out meiotic analyses in metaphase I (MI) and metaphase II (MII) spermatocytes from three fertile donors. Testicular biopsy was obtained during a vasectomy procedure.results: We examined a total of 317 MI and 248 MII spermatocytes. The frequency of numerical chromosome abnormalities at MII (14.5%) was 5.5 times higher than at MI (2.5%). We observed 88 (27.7%) spermatocytes I with chromosome bivalents with a low chiasma count, usually small chromosomes displaying two separated univalents. Chromosomes X, Y and 21 were the most commonly found as achiasmate chromosomes at MI and the most frequently involved in disomy at MII. Hyperploidy frequency in spermatocytes II (disomy) was significantly higher (P , 0.001) than that found in spermatocytes I (trisomy).conclusions: Achiasmate non-disjunction and premature separation of sister chromatids appear to be the two main non-disjunction mechanisms during the first meiotic division in human spermatogenesis, and both mechanisms contribute equally to the genesis of aneuploidy. The elevated frequencies of disomy detected in spermatocytes II are significantly higher than those previously described in human spermatozoa, suggesting the existence of a postmeiotic checkpoint monitoring numerical abnormalities.

show abstract

“…Garcia-Cruz and colleagues [2010a] in their FISH study of 103 MII oocytes donated by women of an average age of 26.6 years reported an aneuploidy rate of 12.6% for these oocytes. Both whole chromosome non-disjunction and unbalanced chromatid predivision were observed to cause abnormalities in the oocytes of young fertile donors [Fragouli et al, 2009;Garcia-Cruz et al, 2010a]. Another unusual phenomenon that could increase the risk of chromosomally abnormal oocytes in younger women is that of gonadal or germinal mosaicism.…”

Section: Age-independent Mechanisms Of Oocyte Aneuploidymentioning

confidence: 99%

Chromosome Abnormalities in the Human Oocyte

Fragouli

Wells

Delhanty

2011

Cytogenet Genome Res

View full text Add to dashboard Cite

Aneuploidy is the most commonly occurring type of chromosome abnormality and the most significant clinically. It arises mostly due to segregation errors taking place during female meiosis and is also closely associated with advancing maternal age. Two main aneuploidy-causing mechanisms have been described: the first involves the non-disjunction of entire chromosomes and can take place during both meiotic divisions, whereas the second involves the premature division of a chromosome into its 2 sister chromatids, followed by their random segregation, upon completion of meiosis I. To elucidate the causal mechanisms of maternally derived aneuploidy and the manner with which they affect the 2 meiotic divisions, a large number of oocytes and their corresponding polar bodies have been examined. Various classical and molecular cytogenetic methods have been employed for this purpose, and valuable data have been obtained. Moreover, research into the gene expression patterns of oocytes according to maturity, maternal age, and chromosome status has provided a unique insight into the complex nature of the biological processes and genetic pathways regulating female meiosis. Findings obtained from the cytogenetic and molecular analysis of oocytes will be reviewed in this article.

show abstract

Cytogenetic analyses of human oocytes provide new data on non-disjunction mechanisms and the origin of trisomy 16

Cited by 29 publications

References 58 publications

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Meiotic non-disjunction mechanisms in human fertile males

Chromosome Abnormalities in the Human Oocyte

Contact Info

Product

Resources

About