The effects of <i>DICER1</i> and <i>DROSHA</i> polymorphisms on susceptibility to recurrent spontaneous abortion

Ghasemi, Marzieh; Rezaei, Mahnaz; Yazdi, Atefeh; Keikha, Narjes; Maruei‐Milan, Rostam; Asadi-Tarani, M; Salimi, Saeedeh

doi:10.1002/jcla.23079

Cited by 8 publications

(8 citation statements)

References 28 publications

(72 reference statements)

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“…DICER1 is essential for the synthesis and biogenesis of miRNAs [36]. Though we identified a de novo frameshift SNV in stillbirth, other polymorphisms in DICER1 were previously shown to be associated with spontaneous miscarriage before 20 weeks' gestation [45] and recurrent pregnancy loss before 14 weeks' gestation [46]. Suggested mechanisms of DICER1 include decidualization of endometrial stroma, which are critical trophoblast invasion and placental function [25,46,47].…”

Section: Plos Onementioning

confidence: 86%

Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study

Workalemahu

Avery²,

Lopez³

et al. 2023

PLoS ONE

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One to two percent of couples suffer recurrent pregnancy loss and over 50% of the cases are unexplained. Whole genome sequencing (WGS) analysis has the potential to identify previously unrecognized causes of pregnancy loss, but few studies have been performed, and none have included DNA from families including parents, losses, and live births. We conducted a pilot WGS study in three families with unexplained recurrent pregnancy loss, including parents, healthy live births, and losses, which included an embryonic loss (<10 weeks’ gestation), fetal deaths (10–20 weeks’ gestation) and stillbirths (≥ 20 weeks’ gestation). We used the Illumina platform for WGS and state-of-the-art protocols to identify single nucleotide variants (SNVs) following various modes of inheritance. We identified 87 SNVs involving 75 genes in embryonic loss (n = 1), 370 SNVs involving 228 genes in fetal death (n = 3), and 122 SNVs involving 122 genes in stillbirth (n = 2). Of these, 22 de novo, 6 inherited autosomal dominant and an X-linked recessive SNVs were pathogenic (probability of being loss-of-function intolerant >0.9), impacting known genes (e.g., DICER1, FBN2, FLT4, HERC1, and TAOK1) involved in embryonic/fetal development and congenital abnormalities. Further, we identified inherited missense compound heterozygous SNVs impacting genes (e.g., VWA5B2) in two fetal death samples. The variants were not identified as compound heterozygous SNVs in live births and population controls, providing evidence for haplosufficient genes relevant to pregnancy loss. In this pilot study, we provide evidence for de novo and inherited SNVs relevant to pregnancy loss. Our findings provide justification for conducting WGS using larger numbers of families and warrant validation by targeted sequencing to ascertain causal variants. Elucidating genes causing pregnancy loss may facilitate the development of risk stratification strategies and novel therapeutics.

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Section: Plos Onementioning

confidence: 86%

Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study

Workalemahu

Avery²,

Lopez³

et al. 2023

PLoS ONE

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“…From the genetic susceptibility point of view, some studies identified an association between Drosha and/or Dicer polymorphisms and the risk of endometriosis ( 33 ) and recurrent spontaneous abortion ( 34 ), conditions known to be associated with adenomyosis ( 35 ). Another hypothesis - although it is not safe to use it to explain the variation in the expression of these proteins in adenomyosis specimens - is the involvement of proteins p53, p63, and p73.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

Ormenezi

Ribeiro‐Silva

Silva

et al. 2022

Braz J Med Biol Res

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The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signedrank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9 ± 3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6 ± 3.2% vs 69.9 ± 3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

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“…The study group consisted of 161 women with idiopathic IRSM, who presented with a history of at least two consecutive pregnancy losses at less than 20 weeks of gestation and 177 healthy women as controls. The enrollment procedure has been described in our previous work [ 29 ]. The local Ethics Committee of Zahedan University of Medical Sciences approved the study (IR.ZAUMS.REC.1399.093).…”

Section: Methodsmentioning

confidence: 99%

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study

et al. 2022

Self Cite

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It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC ( OR = 0.029 ) and allelic C vs. T ( OR = 0.028 ) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA ( OR = 2.81 for rs2961920) and codominant GG vs. AA ( OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

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The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion

Cited by 8 publications

References 28 publications

Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study

Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study

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