To err (meiotically) is human: the genesis of human aneuploidy

Abstract

Aneuploidy (trisomy or monosomy) is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies. Most aneuploid conceptuses perish in utero, which makes this the leading genetic cause of pregnancy loss. However, some aneuploid fetuses survive to term and, as a class, aneuploidy is the most common known cause of mental retardation. Despite the devastating clinical consequences of aneuploidy, relatively little is known of how trisomy and monosomy originate in humans. However, recent molecular and cytogenetic approaches are now beginning to shed light on the non-disjunctional processes that lead to aneuploidy.

Meiotic recombination and male infertility: from basic science to clinical reality?

“…63,64 This finding has obvious clinical ramifications given the fact that aneuploidy, albeit predominantly maternal in origin (except for the sex chromosomes), is the leading cause of pregnancy loss and developmental disabilities in humans. 47 Increased aneuploidy frequencies in infertile men have been reported for all investigated chromosomes. It should be noted that the nuclear position the chromosome probe occupies and the probe signal size has been suggested to influence the perceived levels of aneuploidy.…”

“…Karyotype abnormalities, be they structural or numerical in nature, are observed in 0.4% of liveborns, but infertility is associated with increased levels of chromosome aberrations 5 affecting 2% of males presenting with fertility problems; 6% of oligozoospermic and 14% of non-obstructive azoospermic (NOA) males. 6 In fact, the most common genetically identifiable cause of male factor infertility is Klinefelter syndrome, which is a condition that arises as the result of an additional sex chromosome (47,XXY) in the somatic karyotype.…”

“…33 Therefore, reduced or absent meiotic recombination may lead to increased sperm aneuploidy frequencies, or even spermatogenic arrest, resulting in infertility. 36,47,48 MEIOTIC GENES INVESTIGATED IN INFERTILE MEN Over 75 genes in male infertility mouse models have been identified that when disturbed, can perturb chromosome pairing and synapsis, recombination, aneuploidy, DNA replication and repair in spermatocytes. 17 However, to date, only a handful of studies investigating meiotic gene mutations in infertile human men have been conducted.…”

Retrieval and in vitro maturation of human oocytes from ovaries removed during surgery for endometrial carcinoma: a novel strategy for human oocyte research

“…In this respect, bilateral salpingo-oopho rectomy as standard treatment [5] for patients with uterine endometrial cancer represents an opportunity to avoid ethical problems associated with other sources of oocytes and obtain usable material for research without impacting the pathological diagnosis of the resected specimen. In humans, meiotic chromosome segregation errors, a major cause of aneuploidy, become dramatically more frequent as women age [4,13]. A common aging-related problem during the maturation of human oocytes is poor sister chromatid cohesion during meiosis I and meiosis II [14].…”

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

“…After chromosome separation, oocytes extrude first polar body (PB1) and are arrested at metaphase II (MII) stage waiting for fertilization. Any error in this process can lead to the failure of meiosis so that the oocyte cannot mature, which in humans is a major cause of pregnancy loss and developmental disabilities (Hassold & Hunt, 2001). …”