Genetic diagnosis of subfertility: the impact of meiosis and maternal effects

Gheldof, Alexander; Mackay, Deborah J G; Cheong, Ying; Verpoest, Willem

doi:10.1136/jmedgenet-2018-105513

Cited by 15 publications

(10 citation statements)

References 171 publications

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“…Besides sister cohesion, many other factors including the states of kinetochore, spindle, checkpoint, environment, and recurrence of DNA damage also have important contributions to chromosome mis-segregation and thus maternal age effect. 134 135 136 137 138 139 140 …”

Section: Co Patterns and The High Frequency Of Human Aneuploidiesmentioning

confidence: 99%

Crossover patterns under meiotic chromosome program

Wang¹,

Shang²,

Liu³

et al. 2021

Asian Journal of Andrology

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Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known “maternal age effect.” However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.

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Section: Co Patterns and The High Frequency Of Human Aneuploidiesmentioning

confidence: 99%

Crossover patterns under meiotic chromosome program

Wang¹,

Shang²,

Liu³

et al. 2021

Asian Journal of Andrology

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“…18,19 Genetic Causes of Poor Oocyte Quality in Young Women with Unexplained Infertility Recent genetic and cell-based studies have identified severe defects in diverse facets of oocyte development that impact oocyte and embryo quality. 30 Many such patients have no detectable abnormalities using conventional testing of sperm, tubes, and ovulation and are therefore categorized as unexplained infertility.…”

Section: Poor Oocyte Quality Independent Of Aging Effectsmentioning

confidence: 99%

“…The patients for whom this type of genetic interrogation might be appropriate could be identified during IVF treatment because of unusually low oocyte maturation, extremely low fertilization, or very poor embryo development. 30 Identifying patients with mutations would help tailor treatment, thereby avoiding interventions unlikely to be beneficial such as those targeted at age-induced oocyte quality decline and would also expedite the transition to more suitable options such as use of donor oocytes.…”

Section: Prospects and Challenges For Diagnosing And Improving Poor Omentioning

confidence: 99%

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

Homer

2020

Semin Reprod Med

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Infertility is described as unexplained when pregnancy does not occur despite ovulation, patent Fallopian tubes, and normal semen parameters. Oocyte developmental competence (or quality) is rate-limiting for pregnancy success as oocytes provide virtually all the cellular building blocks including mitochondria required during embryogenesis. However, available tests estimate oocyte numbers (anti-Müllerian hormone, follicle-stimulating hormone and antral follicle count) and ovulation (luteal phase serum progesterone) but not the third, and most pivotal, oocyte-specific parameter, quality. Severe depletion of the follicular reserve manifests as premature ovarian insufficiency and is an obvious cause of anovulation with overt symptoms and clear diagnostic criteria. In contrast, there are no biomarkers of poor oocyte quality other than through in vitro fertilization when readouts of oocyte quality such as preimplantation embryo development can be assessed. The most common cause of poor oocyte quality is natural aging, which is strongly tied to reduced oocyte mitochondrial efficiency and increased oxidative stress. In younger women, quality may also be impaired due to accelerated aging or sporadic genetic mutations which cause severe defects during oocyte and embryo development. Thus, poor oocyte quality often provides an explanation for infertility, but because it cannot be measured using conventional tests, many cases of infertility are often incorrectly labeled “unexplained.” Since female age remains the best predictor of oocyte quality, age over 37 years should be considered an independent diagnostic criterion.

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“…The alteration of the meiotic program is at the basis of an important number of fertility problems ( Handel and Schimenti, 2010 ; Hann et al, 2011 ; Geisinger and Benavente, 2016 ; Gheldof et al, 2019 ; Veitia, 2020 ) and other pathologies (e.g., Tsui and Crismani, 2019 ), including cancer ( Feichtinger and McFarlane, 2019 ). Therefore, the need to improve the knowledge on the molecular groundwork of meiosis in mammals is obvious.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics of Meiosis in the Male Mouse

Geisinger

Rodríguez-Casuriaga

Benavente

2021

Front. Cell Dev. Biol.

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Molecular studies of meiosis in mammals have been long relegated due to some intrinsic obstacles, namely the impossibility to reproduce the process in vitro, and the difficulty to obtain highly pure isolated cells of the different meiotic stages. In the recent years, some technical advances, from the improvement of flow cytometry sorting protocols to single-cell RNAseq, are enabling to profile the transcriptome and its fluctuations along the meiotic process. In this mini-review we will outline the diverse methodological approaches that have been employed, and some of the main findings that have started to arise from these studies. As for practical reasons most studies have been carried out in males, and mostly using mouse as a model, our focus will be on murine male meiosis, although also including specific comments about humans. Particularly, we will center on the controversy about gene expression during early meiotic prophase; the widespread existing gap between transcription and translation in meiotic cells; the expression patterns and potential roles of meiotic long non-coding RNAs; and the visualization of meiotic sex chromosome inactivation from the RNAseq perspective.

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Genetic diagnosis of subfertility: the impact of meiosis and maternal effects

Cited by 15 publications

References 171 publications

Crossover patterns under meiotic chromosome program

Crossover patterns under meiotic chromosome program

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

Transcriptomics of Meiosis in the Male Mouse

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