Effect of steroid hormone receptor gene variants <scp><i>PROGINS</i></scp> (Alu insertion) and <scp><i>PGR</i></scp> C/T (rs1042839) as a risk factor for recurrent pregnancy loss in Kashmiri population (North India)

Khan, Nebela; Zargar, Mahrukh Hameed; Ahmed, Rehana; Godha, Meena; Ahmad, Asif; Afroze, Dil; Masoodi, Shariq Rashid

doi:10.1111/jog.15054

Cited by 6 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, MCM4 dysregulation causes genomic instability, and increases lethality of murine embryos [ 57 ]. Alternatively, dysregulated PGR expression was related to severe preeclampsia [ 58 ] and predisposition to RPL [ 59 ]. Among the upregulated genes, elevated CYP24A1 was observed in spontaneous miscarriage [ 60 ] and preeclamptic placentas [ 61 ]; CXCL14 is implicated in insulin [ 62 ] and inhibited trophoblast attachment and outgrowth, disrupting the establishment of pregnancy [ 63 ]; and CDKN2A and CLCNKA were respectively associated with gestational diabetes [ 64 ] and IGF-1 deficiency [ 65 ], while PTAFR induced preterm delivery in mice [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

Juárez-Barber,

Corachán,

Carbajo-García

et al. 2024

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Background Women with adenomyosis are characterized by having defective decidualization, impaired endometrial receptivity and/or embryo-maternal communication, and implantation failure. However, the molecular mechanisms underlying adenomyosis-related infertility remain unknown, mainly because of the restricted accessibility and the difficult preservation of endometrial tissue in vitro. We have recently shown that adenomyosis patient-derived endometrial organoids, maintain disease-specific features while differentiated into mid-secretory and gestational endometrial phase, overcoming these research barriers and providing a robust platform to study adenomyosis pathogenesis and the associated molecular dysregulation related to implantation and pregnancy disorders. For this reason, we aim to characterize the dysregulated mechanisms in the mid-secretory and gestational endometrium of patients with adenomyosis by RNA-sequencing. Methods Endometrial organoids were derived from endometrial biopsies collected in the proliferative phase of women with adenomyosis (ADENO) or healthy oocyte donors (CONTROL) (n = 15/group) and differentiated into mid-secretory (-SECorg) and gestational (-GESTorg) phases in vitro. Following RNA-sequencing, the significantly differentially expressed genes (DEGs) (FDR < 0.05) were identified and selected for subsequent functional enrichment analysis and QIAGEN Ingenuity Pathway Analysis (IPA). Statistical differences in gene expression were evaluated with the Student’s t-test or Wilcoxon test. Results We identified 1,430 DEGs in ADENO-SECorg and 1,999 DEGs in ADENO-GESTorg. In ADENO-SECorg, upregulated genes included OLFM1, FXYD5, and RUNX2, which are involved in impaired endometrial receptivity and implantation failure, while downregulated genes included RRM2, SOSTDC1, and CHAC2 implicated in recurrent implantation failure. In ADENO-GESTorg, upregulated CXCL14 and CYP24A1 and downregulated PGR were related to pregnancy loss. IPA predicted a significant inhibition of ID1 signaling, histamine degradation, and activation of HMGB1 and Senescence pathways, which are related to implantation failure. Alternatively, IPA predicted an inhibition of D-myo-inositol biosynthesis and VEGF signaling, and upregulation of Rho pathway, which are related to pregnancy loss and preeclampsia. Conclusions Identifying dysregulated molecular mechanisms in mid-secretory and gestational endometrium of adenomyosis women contributes to the understanding of adenomyosis-related implantation failure and/or pregnancy disorders revealing potential therapeutic targets. Following experimental validation of our transcriptomic and in silico findings, our differentiated adenomyosis patient-derived organoids have the potential to provide a reliable platform for drug discovery, development, and personalized drug screening for affected patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

Juárez-Barber,

Corachán,

Carbajo-García

et al. 2024

Reprod Biol Endocrinol

View full text Add to dashboard Cite

show abstract

“…На сьогоднішній день роль генетичних факторів у розвитку акушерсько-гінекологічної патології недостатньо вивчена. Відкритим залишається питання ролі гена PROGINS в генезі повторних репродуктивних втрат [7,15].…”

unclassified

Genetic Aspects of Adverse Consequences of Pregnancy With Isthmic-Cervinal Insufficiency

ISMAILOV¹

2022

AAGU

View full text Add to dashboard Cite

According to modern ideas, both physiological and pathological processes are the result of complex interactions of genetic and epigenetic factors. Among the publications of recent years, there are no studies on the connection of PROGINS and ESR1 gene polymorphisms or gene methylation with ICI and adverse pregnancy outcomes on its background, which prompted us to conduct research in this direction. The aim of the study. To assess the influence of genetic and eugenetic factors on adverse pregnancy outcomes in isthmic-cervical insufficiency (ICI). Research material and methods. comprehensively examined 20 pregnant women with ICI, the correction of which was carried out with the use of a cerclage (main group), in which 2 subgroups were distinguished: ICI1 - 10 women with ICI and an unfavorable end of pregnancy (miscarriage before 22 weeks of pregnancy in 4 women and premature birth in 6 patients ) and ICI2 – 20 patients in whom delivery was urgent (after 37 weeks). A molecular genetic analysis of PGR gene variants (Alu insertion), ESR1 (A351G, rs 9340799) and an epigenetic study of methylation of the promoter region of the estrogen receptor α (ESR1) gene was performed. The results. Loss of pregnancy and premature birth in ICI can be caused not only by a decrease in hormone levels, but also by a violation of hormonalreceptive relationships. The probability of genetic conditioning of disorders of receptive progesterone and estrogen mechanisms in patients with ICI has been established. The presence in a pregnant woman of the mutant T2 allele of the PGR polymorphism (Alu-insertion) and the combination of homozygous genotypes T2T2+ GG of the polymorphic variants of the PGR (Alu-insertion) and ESR1 (A351G rs9340799) genes can be markers of a high risk of adverse pregnancy termination in ICI. In addition, the change in gene expression can be caused by epigenetic disorders, namely gene methylation: hypermethylation of the promoter region of the estrogen receptor α (ESR1) gene was detected in 40% of women with ICI and pregnancy loss in the II trimester or premature birth, which is 4 times higher than the rate women with ICI and normal termination of pregnancy. Conclusions. Adverse pregnancy outcomes with ICI can be caused by genetic (presence of a mutant T2 allele of the PGR polymorphism and combinations of homozygous T2T2+ GG genotypes of polymorphic variants of the PGR Alu-insertion and ESR1 A351G genes) and epigenetic factors (hypermethylation of the promoter region of the estrogen receptor α ESR1 gene). However, these results are preliminary and require further indepth studies on larger data samples.

show abstract

Association of estrogen receptor and progesterone receptor genetic polymorphisms with recurrent pregnancy loss: A systematic review and meta-analysis

Huang,

Yin,

Song

et al. 2024

European Journal of Obstetrics & Gynecology and Reproductiv

View full text Add to dashboard Cite

Effect of steroid hormone receptor gene variants PROGINS (Alu insertion) and PGR C/T (rs1042839) as a risk factor for recurrent pregnancy loss in Kashmiri population (North India)

Cited by 6 publications

References 27 publications

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

Genetic Aspects of Adverse Consequences of Pregnancy With Isthmic-Cervinal Insufficiency

Association of estrogen receptor and progesterone receptor genetic polymorphisms with recurrent pregnancy loss: A systematic review and meta-analysis

Contact Info

Product

Resources

About