A novel homozygous variant in <scp><i>NLRP5</i></scp> is associate with human early embryonic arrest in a consanguineous Chinese family

Xu, Yao; Qian, Ying; Yu, Liu; Wang, Qiaofeng; Wang, Rongxiang; Zhou, Yiwen; Zhang, Caixia; Pang, Zhi; Ye, Hongjuan; Xue, Songguo; Sun, Lihua

doi:10.1111/cge.13744

Cited by 30 publications

(16 citation statements)

References 19 publications

(24 reference statements)

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“…Additionally, KHDC3L , NLRP2 , NLRP5 , and NLRP7 variants were successively indicated to cause abnormal fertilization or embryonic arrest 9‐12 . However, there were no ZBED3 and OOEP related variants reported.…”

Section: Discussionmentioning

confidence: 99%

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Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest

Zheng

Dai

et al. 2020

Clinical Genetics

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The subcortical maternal complex (SCMC) is an oocyte‐to‐embryo‐specific maternal functional module. Some variants of SCMC genes that contribute to preimplantation embryonic arrest have been identified. However, more novel variants should be identified to broaden the genetic and phenotypic spectrum of SCMC genes and establish their roles in embryonic development. We identified 13 novel variants in the SCMC genes, TLE6, NLRP5, NLRP2, and PADI6, from 10 of a total of 50 infertile females with recurrent preimplantation embryonic arrest. Six variants in TLE6 were found in five patients with embryonic arrest, accompanied by direct cleavage and severe fragmentation at the cleavage stage. Three patients carried NLRP5 variants, and one patient each who carried NLRP2 and PADI6 variants had subsequent poor or failed fertilization and cleavage arrest with a relatively lower ratio of severely fragmented embryos. Our findings expand the genetic and phenotypic spectrum of SCMC genes associated with human embryogenesis and might help lay the foundation for the genetic diagnosis of female infertility.

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Section: Discussionmentioning

confidence: 99%

“…Disrupting SCMC genes in mice causes embryonic arrest 5 . Variants in human SCMC genes are associated with embryonic arrest 6‐15 . However, these variants can account for failed pregnancies only a few patients.…”

Section: Introductionmentioning

confidence: 99%

Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest

Zheng

Dai

et al. 2020

Clinical Genetics

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“…Females carrying defective MEGs are healthy, but at risk of reproductive failure due to early developmental arrest or imprinting disorders of their offspring [31]. Recently, human genetic studies confirmed the involvement of several MEGs in reproductive disorders, including primary infertility due to preimplantation embryonic lethality [32][33][34][35][36]. Playing such important roles in embryo development, MEGs are potential targets of age-associated changes in aging oocytes.…”

Section: Expression Of Maternal Effect Genes In the Aging Oocytementioning

confidence: 99%

Oocyte aging: looking beyond chromosome segregation errors

Bebbere

Coticchio²,

Borini³

et al. 2022

J Assist Reprod Genet

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The age‐associated decline in female fertility is largely ascribable to a decrease in oocyte quality. This phenomenon is multifaceted and influenced by numerous interconnected maternal and environmental factors. An increase in the rate of meiotic errors is the major cause of the decline in oocyte developmental competence. However, abnormalities in the ooplasm accumulating with age — including altered metabolism, organelle dysfunction, and aberrant gene regulation — progressively undermine oocyte quality. Stockpiling of maternal macromolecules during folliculogenesis is crucial, as oocyte competence to achieve maturation, fertilization, and the earliest phases of embryo development occur in absence of transcription. At the same time, crucial remodeling of oocyte epigenetics during oogenesis is potentially exposed to interfering factors, such as assisted reproduction technologies (ARTs) or environmental changes, whose impact may be enhanced by reproductive aging. As the effects of maternal aging on molecular mechanisms governing the function of the human oocyte remain poorly understood, studies in animal models are essential to deepen current understanding, with translational implications for human ARTs. The present mini review aims at offering an updated and consistent view of cytoplasmic alterations occurring in oocytes during aging, focusing particularly on gene and epigenetic regulation. Appreciation of these mechanisms could inspire solutions to mitigate/control the phenomenon, and thus benefit modern ARTs.

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“…Various mechanisms leading to arrested development have been proposed coupled by numerous explanations on why these mechanisms may be instigated [ 9 ]. One of the most prominent theories views arrest as a protective mechanism for averting further development of poor-quality embryos [ 9 , 10 , 11 ]. Another hypothesis suggests that other than developmental arrest reflecting a predestined intrinsic scenario of natural selection processes where poor-quality embryos are “cut-off”, we should also consider the possibility that it is the demanding nature of reaching these milestones itself coupled by the respective in vitro culture laboratory conditions that play an important role in failure of embryos to reach these milestones and arrest [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research

Sfakianoudis¹,

Maziotis

Karantzali

et al. 2021

IJMS

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Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos’ arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field.

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A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family

Cited by 30 publications

References 19 publications

Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest

Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest

Oocyte aging: looking beyond chromosome segregation errors

Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research

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