A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition

Lu, Xukun; Gao, Zheng; Qin, Dandan; Li, Lei

doi:10.1016/j.molmed.2017.09.004

Cited by 78 publications

(83 citation statements)

References 68 publications

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“…It has been known that the SCMC plays an important role during embryonic development. SCMC in oocytes regulate the RNA metabolism and zygotic genome activation, which is essential for normal embryonic development 25. In this study, mutations in NLRP2 and NLRP5 lead to unstable proteins.…”

Section: Discussionmentioning

confidence: 85%

Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest

Wang

Chen

et al. 2019

J Med Genet

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BackgroundSuccessful human reproduction requires normal spermatogenesis, oogenesis, fertilisation and early embryonic development, and abnormalities in any of these processes will result in infertility. Early embryonic arrest is commonly observed in infertile patients with recurrent failure of assisted reproductive technology (ART). However, the genetic basis for early embryonic arrest is largely unknown.ObjectiveWe aim to identify genetic causes of infertile patients characterised by early embryonic arrest.MethodsWe pursued exome sequencing in a proband with embryonic arrest from the consanguineous family. We further screened candidate genes in a cohort of 496 individuals diagnosed with early embryonic arrest by Sanger sequencing. Effects of mutations were investigated in HeLa cells, oocytes and embryos.ResultsWe identified five independent individuals carrying biallelic mutations in NLRP2. We also found three individuals from two families carrying biallelic mutations in NLRP5. These mutations in NLRP2 and NLRP5 caused decreased protein expression in vitro and in oocytes and embryos.Conclusions NLRP2 and NLRP5 are novel mutant genes responsible for human early embryonic arrest. This finding provides additional potential diagnostic markers for patients with recurrent failure of ART and helps us to better understand the genetic basis of female infertility characterised by early embryonic arrest.

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Section: Discussionmentioning

confidence: 85%

Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest

Wang

Chen

et al. 2019

J Med Genet

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“…Padi6 knockout in mice leads to infertility that affects only null females [13]. Oocytes from Padi6 −/− lack a specialized cytoskeletal structure called cytoplasmic lattices (CPL) and consequently have abnormal organelle positioning and redistribution, reduced amounts of ribosomal and messenger RNA, altered de novo protein synthesis, and impaired embryonic genome activation [13][14][15]. In mice, PADI6 colocalizes with KHDC3 (the ortholog of human KHDC3L) and NLRP5 and is part of the SCMC.…”

Section: Resultsmentioning

confidence: 99%

Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles

Qian¹,

Nguyen

Rezaei

et al. 2018

Eur J Hum Genet

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Recurrent hydatidiform moles (RHM) are aberrant human pregnancies characterized by absence of, or abnormal, embryonic development, hydropic degeneration of chorionic villi, and hyperproliferation of the trophoblast. Biallelic mutations in two maternal-effect genes, NLRP7 and KHDC3L, underlie the causation of RHM in 60% of patients. We performed exome sequencing on a patient with six pregnancy losses, two miscarriages and four HM, and found no variants that affect the functions of the known genes. We found biallelic missense variants that affect conserved amino acids in PADI6 and segregate with the disease phenotype in the family. PADI6 is another maternal-effect gene and a member of the subcortical maternal complex that has been shown to have recessive variants that affect the gene function in four unrelated women with infertility who also experienced early embryonic arrest during preimplantation development after IVF. We demonstrated that PADI6 co-localizes with NLRP7 in human oocytes and preimplantation embryos and reviewed the morphology and genotypes of four products of conception from our patient. Our data expand the involvement of PADI6 to other forms of reproductive loss and highlight the commonality between infertility, miscarriages, and molar pregnancies, in some cases.

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“…Many maternal effect genes in mammals have been described that impact key early processes, which, when disrupted, are associated with early embryo demise (Condic, 2016; Lu, Gao, Qin, & Li, 2017). Although the study of such mutations is valuable for understanding essential early developmental processes, its relevance to understanding long‐term phenotypic effects is limited.…”

Section: Introductionmentioning

confidence: 99%

Listening to mother: Long‐term maternal effects in mammalian development

Ruebel

Latham

2020

Molecular Reproduction Devel

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The oocyte is a complex cell that executes many crucial and unique functions at the start of each life. These functions are fulfilled by a unique collection of macromolecules and other factors, all of which collectively support meiosis, oocyte activation, and embryo development. This review focuses on the effects of oocyte components on developmental processes that occur after the initial stages of embryogenesis. These include long-term effects on genome function, metabolism, lineage allocation, postnatal progeny health, and even subsequent generations.Factors that regulate chromatin structure, genome programming, and mitochondrial function are elements that contribute to these oocyte functions. K E Y W O R D S chromatin, embryo gene regulation, maternal effect, oocyte 400 |

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A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition

Cited by 78 publications

References 68 publications

Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest

Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest

Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles

Listening to mother: Long‐term maternal effects in mammalian development

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