Genetic and<i>in silico</i>analysis show a role of<i>SMAD3</i>on recurrent pregnancy loss

Bremm, João Matheus; Michels, Marcus Silva; Rengel, Bruna Duarte; Gomes, F. G. F. L. R.; Fraga, Lucas Rosa; Sanseverino, Maria Teresa Vieira

doi:10.1080/14647273.2021.1922764

Cited by 4 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TGF-βs-through activation of downstream signaling mediators-and SMAD2/3 are triggering factors for preeclampsia, resulting in abnormal placental development [86,87]. SMAD3 is further involved in key gestational processes, immune regulation, and inflammation and its altered expression may be associated with recurrent pregnancy loss [88] and preterm birth [89]. Accordingly, our gestational adenomyosis organoids (imitating early pregnancy) showed increased levels of TGF-β2 and SMAD3, recapitulating adenomyosis tissue characteristics.…”

Section: Discussionmentioning

confidence: 71%

Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility

Juárez‐Barber

Francés-Herrero

Corachán

et al. 2022

JPM

View full text Add to dashboard Cite

Adenomyosis is related to infertility and miscarriages, but so far there are no robust in vitro models that reproduce its pathological features to study the molecular mechanisms involved in this disease. Endometrial organoids are in vitro 3D models that recapitulate the native microenvironment and reproduce tissue characteristics that would allow the study of adenomyosis pathogenesis and related infertility disorders. In our study, human endometrial biopsies from adenomyosis (n = 6) and healthy women (n = 6) were recruited. Organoids were established and hormonally differentiated to recapitulate midsecretory and gestational endometrial phases. Physiological and pathological characteristics were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, and ELISA. Secretory and gestational organoids recapitulated in vivo glandular epithelial phenotype (pan-cytokeratin, Muc-1, PAS, Laminin, and Ki67) and secretory and gestational features (α-tubulin, SOX9, SPP1, PAEP, LIF, and 17βHSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17βHSD2 compared with control organoids. Our results demonstrate that organoids derived from endometria of adenomyosis patients and differentiated to secretory and gestational phases recapitulate native endometrial-tissue-specific features and disease-specific traits. Adenomyosis-derived organoids are a promising in vitro preclinical model to study impaired implantation and pregnancy disorders in adenomyosis and enable personalized drug screening.

show abstract

Section: Discussionmentioning

confidence: 71%

Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility

Juárez‐Barber

Francés-Herrero

Corachán

et al. 2022

JPM

View full text Add to dashboard Cite

show abstract

“…Research has demonstrated that SNPs at the Smad3 gene locus are associated with RPL. Abnormal expression of the Smad3 gene can disrupt steroid hormone regulation and embryo implantation processes by impacting the Smad3-dependent signaling pathway, ultimately resulting in PL [ 65 ]. Likewise, bioinformatics investigation reveals that SMAD 3 is one of the central genes implicated in the onset of GDM [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

Han,

Wu,

Bian

et al. 2024

Heliyon

View full text Add to dashboard Cite

“…Several studies have shown a possible association between polymorphisms in TGF-β1, TGF-β2, and TGF-β signaling pathway genes and susceptibility to many diseases. [18][19][20][21] Many genetic studies on TGF-β signaling pathway gene polymorphisms also suggest their possible involvement in the pathogenesis of URSA, [22][23][24] however, these reports are controversial and inconclusive. In the present study, we screened 7 related gene loci on the TGF-β signaling pathway for study, and the results showed that the IL-6 gene -174G/C locus (rs1800795) and the TGF-β1 gene -509T/C locus (rs1800469) had significant differences in genotype and allele distribution frequencies between the case and control groups, and presumably their genetic polymorphisms may be associated with URSA.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…[70] Bremm conducted a case-control study of 149 women with URSA and 159 control women and found that the C allele of the C.207-19370T > C (rs17293443) locus of the Smad3 gene was less frequent in the case group than in the control group and that CC and CT genotypes were associated with a lower risk of URSA, demonstrating that Smad3 gene polymorphisms may influence URSA susceptibility. [24] SMAD1/5 induces bone repair and bone and cartilage formation, and it is essential in embryonic development, mesoderm formation and the developmental shaping of various other organ systems. SMAD1/5 gene research has focused on the regulatory effects on the skeletal system, nervous system, and tumors, but little research has been done on the relationship with recurrent miscarriage.…”

Section: Smad1 Gene C*149(exon7)a/c (Rs28397904)mentioning

confidence: 99%

See 1 more Smart Citation

Correlation of TGF-β signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion

Xue,

Jiang,

Gao

et al. 2023

Medicine

View full text Add to dashboard Cite

Background: The association of key genes in the transforming growth factor-β (TGF-β) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. Objective: To investigate the association of gene polymorphisms related to the TGF-β signaling pathway in URSA women. Methods: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-β1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. Results: Among the 7 loci of IL-6, TGF-β1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-β1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. Conclusion: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-β1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

show abstract

Genetic andin silicoanalysis show a role ofSMAD3on recurrent pregnancy loss

Cited by 4 publications

References 38 publications

Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility

Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

Correlation of TGF-β signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion

Contact Info

Product

Resources

About