A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage

Lou, Chao; Goodier, John; Qiang, Rong

doi:10.1186/s12958-020-0564-x

Cited by 17 publications

(10 citation statements)

References 188 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formation of primordial germ cells (PGS) in mice occurs on E7.25 (Figures 3 and 4) [163][164][165][166][167]. In PGS, DNA undergoes global demethylation, which occurs on day E8.5 of embryogenesis and lasts until E13.5, when PGS are grouped into the genital ridge [168][169][170][171]. Demethylation leads to activation of IAP repeats, however, L1 remains silent at these stages [170].…”

Section: Regulation Of L1 In Germ Cells In Micementioning

confidence: 99%

Factors Regulating the Activity of LINE1 Retrotransposons

Protasova

Andreeva

Rogaev

2021

Genes

View full text Add to dashboard Cite

LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of the activity of L1 elements. The contribution of various factors controlling the expression and distribution of L1 elements in the genome occurs at all stages of the retrotransposition. The regulation of L1 elements at the transcriptional, post-transcriptional and integration into the genome stages is described in detail. Finally, this review also focuses on the evolutionary aspects of L1 accumulation and their interplay with the host regulation system.

show abstract

Section: Regulation Of L1 In Germ Cells In Micementioning

confidence: 99%

Factors Regulating the Activity of LINE1 Retrotransposons

Protasova

Andreeva

Rogaev

2021

Genes

View full text Add to dashboard Cite

show abstract

“…Finally, this report demonstrates the detrimental consequences of pathogenic variants in KIDINS220 that might contribute to an increased frequency of miscarriages with a total of eight miscarriages described in our family. In the cases of recurrent pregnancy loss, cause can be identified in only about 50% of cases (Najafi et al, 2019; Rajcan‐Separovic et al, 2010); additionally, the genetic causes of recurrent miscarriage are poorly understood (Lou, Goodier, & Qiang, 2020). During embryonic development, a single lethal gene mutation may also lead to death of the embryo (Colley et al, 2019; Perez‐Garcia et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant

El-Dessouky

Issa

Aboulghar

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Kinase D-interacting substrate of 220 kDa (KIDINS220) is a transmembrane protein playing integral role in growth mediating pathways in the nervous and cardiovascular systems. KIDINS220 heterozygous truncating variants that affect the protein's C-terminus have been associated with a phenotype, so far described only in few unrelated children, including spastic paraplegia, intellectual disability, nystagmus, and obesity. More recently, a homozygous, more N-terminal truncating variant in KIDINS220 gene was suggested to be associated with enlarged cerebral ventricles and limb contractures in three fetuses from a consanguineous family. We confirm the latter finding by presenting the first detailed prenatal identification of a fetal phenotype associated with novel homozygous deleterious frameshift variant in KIDINS220 gene in a consanguineous healthy Egyptian couple. History of unexplained seven miscarriages and a similar stillbirth were recorded. Prenatal ultrasonography revealed limb contractions and ventriculomegaly; in addition to previously unreported cerebellar anomalies, cardiac anomalies and hydrops fetalis. These findings represent an expansion of clinical and molecular spectrum associated with KIDINS220 variants and broaden our understanding of genotype-phenotype relationships in lethal congenital contractures syndromes and associated severe abnormal embryological development. More generally, our study adds KIDINS220 to the rare group of genes which may cause disease by either of two distinct mutational mechanisms.

show abstract

“…These costly investigations and therapies merit rigorous examination in RCTs prior to recommendation 130 . Genes have been identified related to implantation and immune pathways in RPL and fertility cohorts which may better direct biomolecular research and identify future genetic or immune therapies [136][137][138][139] .…”

Section: Male Fertilitymentioning

confidence: 99%

Infertility and subsequent recurrent miscarriage: Current state of the literature and future considerations for practice and research

Hennessy

O’Donoghue

2021

HRB Open Res

View full text Add to dashboard Cite

Background: Recurrent miscarriage (RM) and infertility are independently associated with adverse pregnancy outcomes, in addition to psychological sequelae. Experiencing pregnancy loss alongside infertility is particularly difficult. International guidance regarding RM is conflicting, and applicability to women with infertility is undetermined. The aim of this study was to: (i) establish if women/couples with a history of infertility are recognised in the literature on the investigation and management of RM, and (ii) determine if the specific needs of women/couples experiencing RM and infertility are ascertained and incorporated into clinical management strategies. Methods: We examined the wide-ranging literature to ascertain what gaps existed. Studies were retrieved through searches of PubMed and Google Scholar up to 21 January 2021 using appropriate controlled vocabulary and combinations of key words. No language or study design restrictions were applied. Results: While women/couples experiencing RM after infertility appear in studies evaluating investigations and proposed treatments, high-quality studies are lacking. Furthermore, they are largely excluded from international clinical guidance and qualitative research. Conclusions: The experiences of women/couples with RM and infertility and their specific care needs within maternity and fertility services are underexplored. It is unclear from current RM guidelines how best to manage and support this complex cohort. Women/couples with infertility and RM are underserved in the literature and in clinical guidance. Further robust studies are warranted to examine pregnancy outcomes, investigations and treatments currently used. Qualitative research is also required to identify their medical and psychological needs to better support this vulnerable group.

show abstract

A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage

Cited by 17 publications

References 188 publications

Factors Regulating the Activity of LINE1 Retrotransposons

Factors Regulating the Activity of LINE1 Retrotransposons

Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant

Infertility and subsequent recurrent miscarriage: Current state of the literature and future considerations for practice and research

Contact Info

Product

Resources

About