Comparison of the ESHRE-ESGE and ASRM classifications of Mullerian duct anomalies in everyday practice.
Ontology highlight
ABSTRACT:
SUBMITTER: Ludwin A
PROVIDER: S-EPMC4325671 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Comparison of the ESHRE-ESGE and ASRM classifications of Müllerian duct anomalies in everyday practice.
Human reproduction (Oxford, England) 20141222 3
<h4>Study question</h4>Does the European Society of Human Reproduction and Embryology-European Society for Gynaecological Endoscopy (ESHRE-ESGE) classification of female genital tract malformations significantly increase the frequency of septate uterus diagnosis relative to the American Society for Reproductive Medicine (ASRM) classification?<h4>Summary answer</h4>Use of the ESHRE-ESGE classification, compared with the ASRM classification, significantly increased the frequency of septate uterus ...[more]
Similar Datasets
Project description:Müllerian duct anomalies (MDAs) are developmental disorders of the Müllerian duct, the embryonic anlage of most of the female reproductive tract. The prevalence of MDAs is 6.7% in the general female population and 16.7% in women who exhibit recurrent miscarriages. Individuals affected by these anomalies suffer from high rates of infertility, first-trimester pregnancy losses, premature labour, placental retention, foetal growth retardation and foetal malpresentations. The aetiology of MDAs is complex and heterogeneous, displaying a range of clinical pictures that generally lack a direct genotype-phenotype correlation. De novo and familial cases sharing the same genomic lesions have been reported. The familial cases follow an autosomal-dominant inheritance, with reduced penetrance and variable expressivity. Furthermore, few genetic factors and molecular pathways underpinning Müllerian development and dysregulations causing MDAs have been identified. The current knowledge in this field predominantly derives from loss-of-function experiments in mouse and chicken models, as well as from human genetic association studies using traditional approaches, such as microarrays and Sanger sequencing, limiting the discovery of causal factors to few genetic entities from the coding genome. In this Review, we summarise the current state of the field, discuss limitations in the number of studies and patient samples that have stalled progress, and review how the development of new technologies provides a unique opportunity to overcome these limitations. Furthermore, we discuss how these new technologies can improve functional validation of potential causative alterations in MDAs.
| S-EPMC8246269 | biostudies-literature
Project description:PurposeThe study aims to investigate the genetic association between paired box gene 2 (PAX2) and mullerian duct anomalies (MDA) in Chinese Han females.MethodsMatrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify the genotypes of three tag single nucleotide polymorphisms (SNPs) in PAX2 in 362 MDA cases and 406 controls.ResultsWe found that one tag SNP (rs12266644) of PAX2 was associated with susceptibility to MDA. The genotype distributions of the SNP rs12266644 have a statistically significant difference in the MDA patients and controls with a p value = 0.008. In the dominant model, we also observed that the GT + TT genotype increased the risk for MDA (p = 0.015, OR = 1.637, 95 % CI = 1.096-2.443).ConclusionThe polymorphism rs12266644 of PAX2 might be a risk factor for MDA in Chinese Han females.
| S-EPMC5330971 | biostudies-literature
Project description:BackgroundMüllerian duct anomalies (MDAs) are congenital developmental disorders that present as a series of abnormalities within the reproductive tracts of females. Genetic factors are linked to MDAs and recent advancements in whole-exome sequencing (WES) provide innovative perspectives in this field. However, relevant mechanism has only been investigated in a restricted manner without clear elucidation of respective observations.MethodsOur previous study reported that 2 of 12 patients with MDAs harbored the CHD1L variant c.348-1G>C. Subsequently, an additional 85 MDAs patients were recruited. Variants in CHD1L were screened through the in-house database of WES performed in the cohort and two cases were identified. One presented with partial septate uterus with left renal agenesis and the other with complete septate uterus, duplicated cervices and longitudinal vaginal septum. The pathogenicity of the discovered variants was further assessed by molecular dynamics simulation and various functional assays.ResultsUltimately, two novel heterozygous CHD1L variants, including a missense variant c.956G>A (p.R319Q) and a nonsense variant c.1831C>T (p.R611*) were observed. The variants were absent in 100 controls. Altogether, the contribution yield of CHD1L to MDAs was calculated as 4.12% (4/97). All three variants were assessed as pathogenic through various functional analysis. The splice-site variant c.348-1G>C resulted in a 11 bp sequence skipping in exon 4 of CHD1L and led to nonsense mediated decay of its transcripts. Unlike WT CHD1L, the truncated R611* protein mislocalized to the cytoplasm, abolish the ability of CHD1L to promote cell migration and failed to interact with PARP1 owing to the loss of macro domain. The R319Q variant exhibited conformational disparities and showed abnormal protein recruitment behavior through laser microirradiation comparing with the WT CHD1L. All these variants impaired the CHD1L function in DNA damage repair, thus participating in MDAs.ConclusionsThe current study not only expands the mutational spectrum of CHD1L in MDAs but determines three variants as pathogenic according to ACMG guidelines with reliable functional evidence. Additionally, the impairment in DNA damage repair is an underlying mechanism involved in MDAs.
| S-EPMC11437902 | biostudies-literature
Project description:Müllerian ducts are paired tubular structures that give rise to most of the female reproductive organs. Any abnormalities in the development and differentiation of these ducts lead to anatomical defects in the female reproductive tract organs categorized as Müllerian duct anomalies. Due to the limited access to fetal tissues, little is understood of human reproductive tract development and the associated anomalies. Although organoids represent a powerful model to decipher human development and disease, such organoids from fetal reproductive organs are not available. Here, we developed organoids from human fetal fallopian tubes and uteri and compared them with their adult counterparts. Our results demonstrate that human fetal reproductive tract epithelia do not express some of the typical markers of adult reproductive tract epithelia. Furthermore, fetal organoids are grossly, histologically, and proteomically different from adult organoids. While external supplementation of WNT ligands or activators in culture medium is an absolute requirement for the adult reproductive tract organoids, fetal organoids are able to grow in WNT-deficient conditions. We also developed decellularized tissue scaffolds from adult human fallopian tubes and uteri. Transplantation of fetal organoids onto these scaffolds led to the regeneration of the adult fallopian tube and uterine epithelia. Importantly, suppression of Wnt signaling, which is altered in patients with Müllerian duct anomalies, inhibits the regenerative ability of human fetal organoids and causes severe anatomical defects in the mouse reproductive tract. Thus, our fetal organoids represent an important platform to study the underlying basis of human female reproductive tract development and diseases.
| S-EPMC9335258 | biostudies-literature
Project description: Not available
| S-EPMC9900425 | biostudies-literature
Project description:Over seventy years ago it was proposed that the fetal testis produces a hormone distinct from testosterone that is required for complete male sexual development. At the time the hormone had not yet been identified but was invoked by Alfred Jost to explain why the Müllerian duct, which develops into the female reproductive tract, regresses in the male fetus. That hormone, anti-Müllerian hormone (AMH), and its specific receptor, AMHR2, have now been extensively characterized and belong to the transforming growth factor-β families of protein ligands and receptors involved in growth and differentiation. Much is now known about the downstream events set in motion after AMH engages AMHR2 at the surface of specific Müllerian duct cells and initiates a cascade of molecular interactions that ultimately terminate in the nucleus as activated transcription factors. The signals generated by the AMH signaling pathway are then integrated with signals coming from other pathways and culminate in a complex gene regulatory program that redirects cellular functions and fates and leads to Müllerian duct regression.
| S-EPMC9201060 | biostudies-literature
Project description:Conventional radiography is widely used for postmortem foetal imaging, but its role in diagnosing congenital anomalies is debated. This study aimed to assess the effectiveness of X-rays in detecting skeletal abnormalities and guiding genetic analysis and counselling. This is a retrospective analysis of all post-abortion diagnostic imaging studies conducted at a centre serving a population of over 300,000 inhabitants from 2008 to 2023. The data were analysed using descriptive statistics. X-rays of 81 aborted foetuses (total of 308 projections; mean: 3.8 projections/examination; SD: 1.79) were included. We detected 137 skeletal anomalies. In seven cases (12.7%), skeletal anomalies identified through radiology were missed by prenatal sonography. The autopsy confirmed radiological data in all cases except for two radiological false positives. Additionally, radiology failed to identify a case of syndactyly, which was revealed by anatomopathology. X-ray is crucial for accurately classifying skeletal abnormalities, determining the causes of spontaneous abortion, and guiding the request for genetic counselling. Formal training for both technicians and radiologists, as well as multidisciplinary teamwork, is necessary to perform X-ray examinations on aborted foetuses and interpret the results effectively.
| S-EPMC11508908 | biostudies-literature
Project description:Müllerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells shortly after commitment of the bipotential gonads to testicular differentiation, causes Müllerian duct (MD) regression. In the fetal female gonads, MIS is not expressed and the MDs will differentiate into the internal female reproductive tract. We have investigated whether dysregulated β-catenin activity affects MD regression by expressing a constitutively activated nuclear form of β-catenin in the MD mesenchyme. We show that constitutively activated (CA) β-catenin causes focal retention of MD tissue in the epididymides and vasa deferentia. In adult mutant mice, the retained MD tissues express α-smooth muscle actin and desmin, which are markers for uterine differentiation. MD retention inhibited the folding complexity of the developing epididymides and usually led to obstructive azoospermia by spermatoceles. The MDs of urogenital ridges from mutant female embryos showed less regression with added MIS in organ culture compared with control MDs when analyzed by whole mount in situ hybridization for Wnt7a as a marker for the MD epithelium. CA β-catenin did not appear to affect expression of either MIS in the embryonic testes or its type II receptor (AMHR2) in the MD mesenchyme nor did it inhibit pSmad1/5/8 nuclear accumulation, suggesting that dysregulated β-catenin must inhibit MD regression independently of MIS signaling. These studies suggest that dysregulated Wnt/β-catenin signaling in the MD mesenchyme might also be a contributing factor in persistent Müllerian duct syndrome, a form of male pseudohermaphroditism, and development of spermatoceles.
| S-EPMC2941287 | biostudies-literature
Project description:A key event during mammalian sexual development is regression of the Müllerian ducts (MDs) in the bipotential urogenital ridges (UGRs) of fetal males, which is caused by the expression of Müllerian inhibiting substance (MIS) in the Sertoli cells of the differentiating testes. The paracrine signaling mechanisms involved in MD regression are not completely understood, particularly since the receptor for MIS, MISR2, is expressed in the mesenchyme surrounding the MD, but regression occurs in both the epithelium and mesenchyme. Microarray analysis comparing MIS signaling competent and Misr2 knockout embryonic UGRs was performed to identify secreted factors that might be important for MIS-mediated regression of the MD. A seven-fold increase in the expression of Wif1, an inhibitor of WNT/β-catenin signaling, was observed in the Misr2-expressing UGRs. Whole mount in situ hybridization of Wif1 revealed a spatial and temporal pattern of expression consistent with Misr2 during the window of MD regression in the mesenchyme surrounding the MD epithelium that was absent in both female UGRs and UGRs knocked out for Misr2. Knockdown of Wif1 expression in male UGRs by Wif1-specific siRNAs beginning on embryonic day 13.5 resulted in MD retention in an organ culture assay, and exposure of female UGRs to added recombinant human MIS induced Wif1 expression in the MD mesenchyme. Knockdown of Wif1 led to increased expression of β-catenin and its downstream targets TCF1/LEF1 in the MD mesenchyme and to decreased apoptosis, resulting in partial to complete retention of the MD. These results strongly suggest that WIF1 secretion by the MD mesenchyme plays a role in MD regression in fetal males.
| S-EPMC4047716 | biostudies-literature
Project description:In mammals, the developing reproductive tract primordium of male and female fetuses consists of the Wolffian duct and the Müllerian duct (MD), two epithelial tube pairs surrounded by mesenchyme. During male development, mesenchyme-epithelia interactions mediate MD regression to prevent its development into a uterus, oviduct, and upper vagina. It is well established that transforming growth factor-? family member anti-Müllerian hormone (AMH) secreted from the fetal testis and its type 1 and 2 receptors expressed in MD mesenchyme regulate MD regression. However, little is known about the molecular network regulating downstream actions of AMH signaling. To identify potential AMH-induced genes and regulatory networks controlling MD regression in a global nonbiased manner, we examined transcriptome differences in MD mesenchyme between males (AMH signaling on) and females (AMH signaling off) by RNA-seq analysis of purified fetal MD mesenchymal cells. This analysis found 82 genes up-regulated in males during MD regression and identified Osterix (Osx)/Sp7, a key transcriptional regulator of osteoblast differentiation and bone formation, as a downstream effector of AMH signaling during MD regression. Osx/OSX was expressed in a male-specific pattern in MD mesenchyme during MD regression. OSX expression was lost in mutant males without AMH signaling. In addition, transgenic mice ectopically expressing human AMH in females induced a male pattern of Osx expression. Together, these results indicate that AMH signaling is necessary and sufficient for Osx expression in the MD mesenchyme. In addition, MD regression was delayed in Osx-null males, identifying Osx as a factor that regulates MD regression.
| S-EPMC6099909 | biostudies-literature