{"title":"Correction to: Comparison of dietary and physical activity behaviors in women with and without polycystic ovary syndrome: a systematic review and meta-analysis of 39 471 women.","authors":"","doi":"10.1093/humupd/dmac036","DOIUrl":"https://doi.org/10.1093/humupd/dmac036","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"29 1","pages":"155"},"PeriodicalIF":13.3,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825261/pdf/dmac036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10505301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Kazemi, Joy Y Kim, Cynthia Wan, Julia D Xiong, Julia Michalak, Isabella B Xavier, Kiran Ganga, Chau Thien Tay, Jessica A Grieger, Stephen A Parry, Lisa J Moran, Marla E Lujan
{"title":"Comparison of dietary and physical activity behaviors in women with and without polycystic ovary syndrome: a systematic review and meta-analysis of 39 471 women.","authors":"Maryam Kazemi, Joy Y Kim, Cynthia Wan, Julia D Xiong, Julia Michalak, Isabella B Xavier, Kiran Ganga, Chau Thien Tay, Jessica A Grieger, Stephen A Parry, Lisa J Moran, Marla E Lujan","doi":"10.1093/humupd/dmac023","DOIUrl":"10.1093/humupd/dmac023","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle (dietary and/or physical activity [PA]) modification is recommended as first-line therapy to manage polycystic ovary syndrome (PCOS). Current recommendations are based on healthy lifestyle practices for the general public since evidence for unique lifestyle approaches in PCOS is limited and low quality.</p><p><strong>Objective and rationale: </strong>We aimed to synthesize evidence on dietary and PA behaviors between women with PCOS and those without PCOS. Primary outcomes were overall diet quality, total energy intake and total PA, and secondary outcomes included macronutrients, micronutrients, food groups, foods, glycemic indices, sedentary time and sitting levels. We conducted this work to identify any unique lifestyle behaviors in women with PCOS that could underlie the propensity of weight gain and obesity in PCOS and be targeted for precision nutrition and PA interventions. These findings could be used to inform future practice recommendations and research that more effectively address complications (weight gain, obesity, diabetes, infertility, cardiovascular disease and mental health) in this high-risk population.</p><p><strong>Search methods: </strong>Databases of MEDLINE, Web of Science, Scopus and CINAHL were searched until 15 February 2022 to identify observational studies documenting dietary and PA behaviors between women with PCOS and without PCOS (Controls). Studies on children, adolescents (<18 years), pregnant or menopausal-aged women (>50 years) were excluded. Data were pooled by random-effects models and expressed as (standardized) mean differences (MD) and 95% CIs. The risk of bias was assessed by the Newcastle-Ottawa scale (NOS).</p><p><strong>Outcomes: </strong>Fifty-four studies (N = 39 471 participants; [n = 8736 PCOS; 30 735 Controls]) were eligible (96%; [52/54] NOS scores ≥ 7). Women with PCOS had higher cholesterol (MD: 12.78, 95% CI: 1.48 to 24.08 mg/day; P = 0.03; I2 = 19%), lower magnesium (MD: -21.46, 95% CI: -41.03 to -1.91 mg/day; P = 0.03; I2 = 76%), and a tendency for lower zinc (MD: -1.08, 95% CI: -2.19 to -0.03 mg/day; P = 0.05; I2 = 96%) intake, despite lower alcohol consumption (MD: -0.95, 95% CI: -1.67 to 0.22 g/day; P = 0.02; I2 = 0%) versus Controls. Also, women with PCOS had lower total PA (standardized mean difference: -0.38, 95% CI: -0.72 to 0.03; P = 0.03; I2 = 98%). Conversely, energy, macronutrients (carbohydrate, fat, protein, fiber), micronutrients (folic acid, iron, calcium, sodium), glycemic index and glycemic load were similar (all: P ≥ 0.06). Most eligible studies reported lower total adherence to healthy eating patterns or poorer consumption of major food groups (grains, fruits, vegetables, proteins, seeds, nuts, dairy) in women with PCOS, as described narratively since variable study methodology did not permit meta-analyses.</p><p><strong>Wider implications: </strong>Collective evidence supports that women with PCOS have a lower overall diet qu","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 6","pages":"910-955"},"PeriodicalIF":14.8,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629501/pdf/dmac023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9877256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natiela Caponi, Luis F O Silva, Marcos L S Oliveira, Dison S P Franco, Matias S Netto, Felipe Vedovatto, Marcus V Tres, Giovani L Zabot, Ederson R Abaide, Guilherme L Dotto
{"title":"Adsorption of basic fuchsin using soybean straw hydrolyzed by subcritical water.","authors":"Natiela Caponi, Luis F O Silva, Marcos L S Oliveira, Dison S P Franco, Matias S Netto, Felipe Vedovatto, Marcus V Tres, Giovani L Zabot, Ederson R Abaide, Guilherme L Dotto","doi":"10.1007/s11356-022-20652-w","DOIUrl":"10.1007/s11356-022-20652-w","url":null,"abstract":"<p><p>The valorization of agro-industrial residues can be improved through their full use, making the production of second-generation ethanol viable. In this scenario, hydrolyzed soybean straw generated from a subcritical water process was applied to the basic fuchsin adsorption. At pH eight, a high adsorption capacity was obtained. The mass test results showed that basic fuchsin's removal and adsorption capacity could be maximized with an adsorbent dosage of 0.9 g L<sup>-1</sup>. The linear driving force model was suitable for predicting the kinetic profile, and the kinetic curves showed that equilibrium was reached with only 30 min of contact time. Besides, the Langmuir model was the best to predict the adsorption isotherms. The thermodynamic parameters revealed a spontaneous and endothermic process. At 328 K, there is maximum adsorption capacity (72.9 mg g<sup>-1</sup>). Therefore, it can be stated that this material could be competitive in terms of adsorption capacity coupled with the idea of full use of waste.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"7 1 1","pages":"68547-68554"},"PeriodicalIF":5.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82953573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Bamford, Amy Barrie, Sue Montgomery, Rima Dhillon-Smith, Alison Campbell, Christina Easter, Arri Coomarasamy
{"title":"Morphological and morphokinetic associations with aneuploidy: a systematic review and meta-analysis.","authors":"Thomas Bamford, Amy Barrie, Sue Montgomery, Rima Dhillon-Smith, Alison Campbell, Christina Easter, Arri Coomarasamy","doi":"10.1093/humupd/dmac022","DOIUrl":"https://doi.org/10.1093/humupd/dmac022","url":null,"abstract":"<p><strong>Background: </strong>A time lapse system (TLS) is utilized in some fertility clinics with the aim of predicting embryo viability and chance of live birth during IVF. It has been hypothesized that aneuploid embryos display altered morphokinetics as a consequence of their abnormal chromosome complement. Since aneuploidy is one of the fundamental reasons for IVF failure and miscarriage, attention has focused on utilizing morphokinetics to develop models to non-invasively risk stratify embryos for ploidy status. This could avoid or reduce the costs associated with pre-implantation genetic testing for aneuploidy (PGT-A). Furthermore, TLS have provided an understanding of the true prevalence of other dysmorphisms. Hypothetically, the incorporation of morphological features into a model could act synergistically, improving a model's discriminative ability to predict ploidy status.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and meta-analysis was to investigate associations between ploidy status and morphokinetic or morphological features commonly denoted on a TLS. This will determine the feasibility of a prediction model for euploidy and summarize the most useful prognostic markers to be included in model development.</p><p><strong>Search methods: </strong>Five separate searches were conducted in Medline, Embase, PubMed and Cinahl from inception to 1 July 2021. Search terms and word variants included, among others, PGT-A, ploidy, morphokinetics and time lapse, and the latter were successively substituted for the following morphological parameters: fragmentation, multinucleation, abnormal cleavage and contraction. Studies were limited to human studies.</p><p><strong>Outcomes: </strong>Overall, 58 studies were included incorporating over 40 000 embryos. All except one study had a moderate risk of bias in at least one domain when assessed by the quality in prognostic studies tool. Ten morphokinetic variables were significantly delayed in aneuploid embryos. When excluding studies using less reliable genetic technologies, the most notable variables were: time to eight cells (t8, 1.13 h, 95% CI: 0.21-2.05; three studies; n = 742; I2 = 0%), t9 (2.27 h, 95% CI: 0.5-4.03; two studies; n = 671; I2 = 33%), time to formation of a full blastocyst (tB, 1.99 h, 95% CI 0.15-3.81; four studies; n = 1640; I2 = 76%) and time to expanded blastocyst (tEB, 2.35 h, 95% CI: 0.06-4.63; four studies; n = 1640; I2 = 83%). There is potentially some prognostic potential in the degree of fragmentation, multinucleation persisting to the four-cell stage and frequency of embryo contractions. Reverse cleavage was associated with euploidy in this meta-analysis; however, this article argues that these are likely spurious results requiring further investigation. There was no association with direct unequal cleavage in an embryo that progressed to a blastocyst, or with multinucleation assessed on Day 2 or at the two-cell stage. However, owing","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 5","pages":"656-686"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J A Wessel,N A Danhof,R van Eekelen,M P Diamond,R S Legro,K Peeraer,T M D'Hooghe,M Erdem,T Dankert,B J Cohlen,C Thyagaraju,B W J Mol,M Showell,M van Wely,M H Mochtar,R Wang
{"title":"Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis.","authors":"J A Wessel,N A Danhof,R van Eekelen,M P Diamond,R S Legro,K Peeraer,T M D'Hooghe,M Erdem,T Dankert,B J Cohlen,C Thyagaraju,B W J Mol,M Showell,M van Wely,M H Mochtar,R Wang","doi":"10.1093/humupd/dmac021","DOIUrl":"https://doi.org/10.1093/humupd/dmac021","url":null,"abstract":"BACKGROUNDIntrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment-covariate interactions to identify couples who benefit most from a particular treatment.OBJECTIVE AND RATIONALEWe performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment-covariate interactions for important baseline characteristics in couples undergoing IUI.SEARCH METHODSWe searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.OUTCOMESSeven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12-1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33-3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05-1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94-1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45-1.96; RR 0.81, 95% CI 0.32-2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when c","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"1136 ","pages":"733-746"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C S Uldbjerg, T Koch, Y-H Lim, L S Gregersen, C S Olesen, A-M Andersson, H Frederiksen, B A Coull, R Hauser, A Juul, E V Bräuner
{"title":"Prenatal and postnatal exposures to endocrine disrupting chemicals and timing of pubertal onset in girls and boys: a systematic review and meta-analysis.","authors":"C S Uldbjerg, T Koch, Y-H Lim, L S Gregersen, C S Olesen, A-M Andersson, H Frederiksen, B A Coull, R Hauser, A Juul, E V Bräuner","doi":"10.1093/humupd/dmac013","DOIUrl":"https://doi.org/10.1093/humupd/dmac013","url":null,"abstract":"<p><strong>Background: </strong>Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established.</p><p><strong>Objective and rationale: </strong>EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs.</p><p><strong>Search methods: </strong>Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys.</p><p><strong>Outcomes: </strong>The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations.</p><p><strong>Wider implications: </strong>Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with ex","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 5","pages":"687-716"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434240/pdf/dmac013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Navigating parent-child disagreement about fertility preservation in minors: scoping review and ethical considerations.","authors":"Michelle Bayefsky,Dorice Vieira,Arthur Caplan,Gwendolyn Quinn","doi":"10.1093/humupd/dmac019","DOIUrl":"https://doi.org/10.1093/humupd/dmac019","url":null,"abstract":"BACKGROUNDOffering fertility preservation (FP) prior to gonadotoxic therapy, including cancer care and gender-affirming treatment, is now considered standard of care. Periodically, parents and children disagree about whether to pursue FP. However, it is unknown how often this occurs and how disagreement is handled when it arises. Moreover, there is no clear guidance on how to resolve these difficult situations.OBJECTIVE AND RATIONALEThe purpose of this scoping review is to provide an overview of available research evidence about parent-child disagreement regarding FP in order to establish that disagreement occurs in practice, understand the basis for disagreement and explore suggestions for how such disputes could be resolved. Based on our findings, we offer a discussion of the ethical principles at stake when disagreement occurs, which can be used to guide clinicians' approaches when these challenging scenarios present.SEARCH METHODSA comprehensive literature search was run in several databases, including PubMed/Medline, Embase and the Cochrane Library. The search was performed in February 2021 and updated in August 2021. Articles were included in the final review if they discussed how parents or children wanted their views on FP taken into account, presented evidence that parent-child discordance regarding FP exists, discussed how to handle disagreement in a particular case or offered general suggestions for how to approach parent-child discordance about FP. Studies were excluded if the patients were adult only (age 18 years and older), pertained to fertility-sparing treatments (e.g. gonad shielding, gonadopexy) rather than fertility-preserving treatments (e.g. testicular tissue cryopreservation, ovarian tissue cryopreservation, oocyte cryopreservation or sperm cryopreservation) or explored the views of clinicians but not patients or parents. Meta-synthesis was used to synthesize and interpret data across included studies and thematic analysis was used to identify common patterns and themes.OUTCOMESIn total, 755 publications were screened, 118 studies underwent full-text review and 35 studies were included in the final review. Of these studies, 7 discussed how parents or children wanted their opinions to be incorporated, 11 presented evidence that discordance exists between parents and children regarding FP, 4 discussed how disagreement was handled in a particular case and 21 offered general suggestions for how to approach parent-child disagreement. There was a range of study designs, including quantitative and qualitative studies, case studies, ethical analyses and commentaries. From the thematic analysis, four general themes regarding FP disagreement emerged, and four themes relating to the ethical principles at stake in parent-child disagreement were identified. The general themes were: adolescents typically desire to participate in FP decision-making; some parents prefer not to involve their children; minors may feel more favorably about FP","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"962 1","pages":"747-762"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oliwia W Mlodawska, Priyanka Saini, J Brandon Parker, Jian-Jun Wei, Serdar E Bulun, Melissa A Simon, Debabrata Chakravarti
{"title":"Epigenomic and enhancer dysregulation in uterine leiomyomas.","authors":"Oliwia W Mlodawska, Priyanka Saini, J Brandon Parker, Jian-Jun Wei, Serdar E Bulun, Melissa A Simon, Debabrata Chakravarti","doi":"10.1093/humupd/dmac008","DOIUrl":"https://doi.org/10.1093/humupd/dmac008","url":null,"abstract":"<p><strong>Background: </strong>Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common benign gynecological tumors and are found in women of reproductive and postmenopausal age. There is an exceptionally high prevalence of this tumor in women by the age of 50 years. Black women are particularly affected, with an increased incidence, earlier age of onset, larger and faster growing fibroids and greater severity of symptoms as compared to White women. Although advances in identifying genetic and environmental factors to delineate these fibroids have already been made, only recently has the role of epigenomics in the pathogenesis of this disease been considered.</p><p><strong>Objective and rationale: </strong>Over recent years, studies have identified multiple epigenomic aberrations that may contribute to leiomyoma development and growth. This review will focus on the most recent discoveries in three categories of epigenomic changes found in uterine fibroids, namely aberrant DNA methylation, histone tail modifications and histone variant exchange, and their translation into altered target gene architecture and transcriptional outcome. The findings demonstrating how the altered 3D shape of the enhancer can regulate gene expression from millions of base pairs away will be discussed. Additionally, translational implications of these discoveries and potential roadblocks in leiomyoma treatment will be addressed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was performed to identify published articles containing keywords relevant to the focus of the review, such as: uterine leiomyoma, uterine fibroids, epigenetic alterations, epigenomics, stem cells, chromatin modifications, extracellular matrix [ECM] organization, DNA methylation, enhancer, histone post-translational modifications and dysregulated gene expression. Articles until September 2021 were explored and evaluated to identify relevant updates in the field. Most of the articles focused on in the discussion were published between 2015 and 2021, although some key discoveries made before 2015 were included for background information and foundational purposes. We apologize to the authors whose work was not included because of space restrictions or inadvertent omission.</p><p><strong>Outcomes: </strong>Chemical alterations to the DNA structure and of nucleosomal histones, without changing the underlying DNA sequence, have now been implicated in the phenotypic manifestation of uterine leiomyomas. Genome-wide DNA methylation analysis has revealed subsets of either suppressed or overexpressed genes accompanied by aberrant promoter methylation. Furthermore, differential promoter access resulting from altered 3D chromatin structure and histone modifications plays a role in regulating transcription of key genes thought to be involved in leiomyoma etiology. The dysregulated genes function in tumor suppression, apoptosis, angiogenesis, ECM formation, a variety o","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"518-547"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247409/pdf/dmac008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}