Development Of Uterine Fibroids Research Articles

Exploring the gut-inflammation connection: A Mendelian randomization study on gut microbiota, inflammatory factors, and uterine fibroids risk

This study employs Mendelian randomization (MR) approach to investigate the potential causal association between genetic variants associated with gut microbiota, inflammatory factors, and the risk of uterine fibroids development. We extracted data on 211 types of gut microbiota, 91 inflammatory factors, and uterine fibroids occurrence from genome-wide association studies and applied the inverse-variance weighted (IVW) method for analysis. To further assess the robustness of our MR analysis, we conducted sensitivity tests including Cochrane’s Q test, the MR-Egger intercept test, the MR-PRESSO global test, and a leave-one-out analysis. IVW analysis identified a potential causal association between 14 types of gut microbiota and 8 inflammatory factors with the risk of uterine fibroids. When using 91 inflammation-related proteins as the outcome variable, 13 proteins demonstrated a potential causal association with uterine fibroids risk (IVW, all P < .05). Additionally, the MR-Egger intercept and MR-PRESSO global tests indicated no evidence of horizontal pleiotropy (P > .05), and the leave-one-out analysis confirmed the robustness of the results. This MR approach suggests that specific gut microbiota and inflammatory factors may have a causal association with the development of uterine fibroids, shedding light on the pathogenesis of uterine fibroids and potentially identifying targets for future therapeutic interventions.

Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids.

SERPINA3 (α-1-antichymotrypsin, AACT, ACT) is produced by the liver and released into plasma in an anti-inflammatory response and plays a role as a modulator of extracellular matrix (ECM) by inhibiting serine proteases. Numerous studies proved an increased level of SERPINA3 in many types of cancer, which could be linked to SERPINA3's anti-apoptotic function. In the context of progressive ECM fibrosis during the development of uterine fibroids, which are one of the most common hypertrophic changes within the uterus, it is interesting to describe the level of SERPINA3 protein in this type of lesion and the surrounding tissues. We used immunohistochemical staining of the SERPINA3 protein and compared the intensity of the signal between the myoma tissue and the surrounding normal tissue. We showed a surprising reduction in the amount of the SERPINA3 protein within uterine fibroids compared to surrounding tissues. This observation sheds new light on the role of this protein in the formation of proliferative changes and suggests that understanding the mechanism of its action may become the basis for the development of new diagnostic and therapeutic tools.

Factors associated with uterine fibroids in women of reproductive age: A cross-sectional study

Background. Uterine fibroids is a benign monoclonal tumor originating from the smooth muscle layer of the uterus. Non-modifiable risk factors for the development of uterine fibroids, such as age, ethnicity, age at menarche, etc, have been studied quite extensively, while the role of many controllable factors remains debatable.The aim of the study. To identify the main modifiable factors associated with uterine fibroids in women of reproductive age living in the Baikal region, including certain ethnic groups.Materials and methods. We carried out a multicenter cross-sectional study in 2016–2019 in institutions of Irkutsk and Bokhan (Irkutsk region) and Ulan-Ude (Republic of Buryatia). The subjects of the study were women to have annual workplace medical examination. The study included 1,347 participants of reproductive age (34.33 ± 6.37 years) who met the inclusion criteria. Among all women included in the study, there were 867 (64.37 %) Caucasians, 361 (26.80 %) Asians, and 119 (8.83%) women of mixed (Caucasian-Asian), ethnicity. The research methods included a questionnaire, general clinical and gynecological examination, and pelvic ultrasound examination.Results. According to our study, the main non-modifiable factors associated with the presence of uterine fibroids were: Asian ethnicity; age at menarche 12–13 years; age of the study participant 40–44 years; menopausal symptoms; adenomyosis. The “controllable” factors included: city residency; body mass index over 40 kg/m2; history of abortions and miscarriages; metabolic syndrome; using combined oral contraceptives; lack of sexual activity; smoking; presence of anumber of occupational hazards.Conclusion. Our study identified the main controllable factors associated with the presence of uterine fibroids in a multiethnic population of women of reproductive age.

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

Association of polymorphic variants of cytokines genes, endothelial growth factor and matrix metalloproteinases with the development of uterine fibroids among russian women

One of the factors in the development of uterine fibroids is a genetic predisposition to its occurrence in some women, but the real molecular genetic mechanisms of this phenomenon remain unknown. Aim of the study was the distribution analysis of gene polymorphism of cytokines TNFα, IL-1β, IL-4, IL-6, IL-10, factors of angiogenesis (vascular endothelial growth factor, VEGF) and remodeling of extracellular matrix (metalloproteinases MMP2, MMP3, MMP9), which are associated with their levels. Material and methods. Genotyping was performed by real-time PCR using commercial test systems SYBR GreenI (Litech, Russia) and TaqMan (Syntol, Russia) in accordance with the instructions of the developer. Cytokine content in blood serum was determined by flow cytometry using microspheres coated with monoclonal antibodies to cytokines (Bio-Plex ProTM Human Cytokine 27-plex Assay), according to the instructions for Bio-Plex 200 (Bio-Rad Laboratories, USA).To evaluate the results obtained, in addition to the generally accepted methods of statistical processing for case – control studies, computational methods of bioinformatics were used for comparative analysis of the diagnostic value of various combined genetic traits. Results. It was shown that the maximum odds ratio value of uterine fibroids development are combined genetic traits that include representatives of all four regulatory factors: cytokines with pro-inflammatory activity, cytokines with anti-inflammatory activity, vascular endothelial growth factors and metalloproteinases (p = 0.002). Conclusions. The presented data reveal the real mechanisms of manifestation of the genetic predisposition of individual women to the uterine fibroids development, associated with the presence of polymorphism of certain genes in their genome, which provide features of the structure of cytokine networks with the predominance of certain activities in the regulation of tissue processes in the uterus. In addition to purely scientific interest, these results indicate the real possibility of their clinical application in the form of prognostic criteria with a certain level of prognostic significance.

UTERINE FIBROIDS AND THE CORRELATION WITH BLACK WOMEN

Uterine fibroids are common benign tumors in the uterus of women of reproductive age and can cause symptoms such as heavy menstrual bleeding, pelvic pain and increased abdominal volume. Studies have shown a higher prevalence of uterine fibroids in black women compared to women of other ethnicities. Understanding the causes of this disparity is fundamental to developing more effective prevention and treatment strategies. Investigating the relationship between the incidence of uterine fibroids and black ethnicity, analyzing the genetic and social factors that may contribute to this correlation and proposing measures to reduce the incidence of uterine fibroids in black women are the aims of this study. This is a systematic literature review using an exploratory and narrative method, with qualitative and quantitative premises. The databases used were PubMed, Scielo, Scopus, Web of Science and the Virtual Health Library. The articles analyzed were selected by exclusion and inclusion criteria, which are set out here, using the health sciences descriptors “uterine fibroids”, “black women and uterine fibroids”, “genetic factors and uterine fibroids” and “environmental factors and uterine fibroids”, reaching a total of 617 articles searched and 9 used in this study. Genetic studies have suggested a genetic predisposition to the development of uterine fibroids in black women, with the identification of genetic variants associated with a higher risk. In addition, social factors such as limited access to quality healthcare, socioeconomic inequalities and exposure to psychosocial stressors may also play an important role. Lack of access to preventive healthcare and unequal access to effective treatments may contribute to a higher prevalence of uterine fibroids in black women. Measures to reduce this disparity include promoting equitable access to healthcare, reproductive health education and public policies that address the underlying causes of health inequalities. The correlation between uterine fibroids and black women highlights the need for integrated approaches that consider both genetic and social factors. Promoting equity in access to health care and implementing public policies aimed at women’s health are key to reducing the incidence of uterine fibroids and improving the quality of life of black women.

Uterine fibroids and longitudinal profiles of the vaginal microbiota in a cohort presenting for transvaginal ultrasound.

Bacterial vaginosis, characterized in part by low levels of vaginal Lactobacillus species, has been associated with pro-inflammatory cytokines which could fuel uterine fibroid development. However, prior work on the associations between uterine fibroids and vaginal bacteria is sparse. Most studies have focused on assessment of individual taxa in a single sample. To address research gaps, we sought to compare short, longitudinal profiles of the vaginal microbiota in uterine fibroid cases versus controls with assessment for hormonal contraceptives (HCs), a possible confounder associated with both protection from fibroid development and increases in Lactobacillus-dominated vaginal microbiota. This is a secondary analysis of 83 reproductive-age cisgender women who presented for transvaginal ultrasound (TVUS) and self-collected mid-vaginal swabs daily for 1-2 weeks before TVUS (Range: 5-16 days, n = 697 samples). Sonography reports detailed uterine fibroid characteristics (N = 21 cases). Vaginal microbiota was assessed by 16S rRNA gene amplicon sequencing and longitudinal microbiota profiles were categorized by hierarchical clustering. We compared longitudinal profiles of the vaginal microbiota among fibroid cases and controls with exact logistic regression. Common indications for TVUS included pelvic mass (34%) and pelvic pain (39%). Fibroid cases tended to be older and report Black race. Cases less often reported HCs versus controls (32% vs. 58%). A larger proportion of cases had low-Lactobacillus longitudinal profiles (48%) than controls (34%). In unadjusted analysis, L. iners-dominated and low-Lactobacillus profiles had higher odds of fibroid case status compared to other Lactobacillus-dominated profiles, however these results were not statistically significant. No association between vaginal microbiota and fibroids was observed after adjusting for race, HC and menstruation. Results were consistent when number of fibroids were considered. There was not a statistically significant association between longitudinal profiles of vaginal microbiota and uterine fibroids after adjustment for common confounders; however, the study was limited by small sample size.

Body Mass Index and Uterine Fibroid Development: A Prospective Study.

Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with a body mass index (BMI) ≥30 kg/m2 into a single category and relied on clinically diagnosed fibroids, which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound. The Study of Environment, Lifestyle & Fibroids followed 1693 Black/African American women, ages 23 to 35 years from Detroit, Michigan, with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates. Compared with BMI <25 kg/m2, those with BMI 30 to <35 kg/m2 had increased fibroid incidence (adjusted hazard ratio, 1.37; 95% CI, 0.96-1.94), those with BMI ≥40 kg/m2 had reduced incidence (adjusted hazard ratio, 0.61; 95% CI, 0.41-0.90). Fibroid growth had mostly small magnitude associations with BMI. BMI has a nonlinear association with fibroid incidence, which could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed.

Influence of nutrition on the course of uterine fibroids

Currently, there is a negative trend in the increase in the incidence of uterine fibroids, often diagnosed at a later date, requiring more invasive laparotomic myomectomy, up to hysterectomy. It was also revealed that the patients had an aggravated premorbid background in the form of obesity and related diseases.The purpose of the study. To study domestic and foreign studies. To identify the features of the course of uterine fibroids in patients with hypersthenic and normosthenic body types.Materials and methods. Anonymous and voluntary questionnaire survey with an in-depth collection of food history, interviews of 260 patients and analysis of their case histories with uterine fibroids who underwent laparoscopic and laparotomic myomectomy were carried out, dividing them into 2 groups according to BMI.Results. In both groups, there was the following distribution according to the presence of pregnancies: 0 – 4 % and 5 %, 1 – 86 % and 84 %, 2 – 10 % and 11 % for groups I and II, respectively (p = 0.041 criterion). 25 % in group I and 31 % in group II had a history of surgery – caesarean section. The presence of inflammatory diseases of the pelvic organs in both groups was 89.3 % and 91.6 %, respectively. Also noted was a high consumption of beef and pork by 10 and 23 %, potatoes by 8 % and 13 %, white cabbage by 12 % and 11 %, bakery products by 21 % and 26 %. Low consumption of seafood and fish products by 35 % and 56 %, dairy products by 44 % and 47 %, absolutely low content of olive oil in the daily diet. The above data are presented for groups I and II, respectively. (criterion p = 0.029-0.054).Сonclusions. Obesity plays a role as a risk factor for the development of uterine fibroids, acting either through hormonal or inflammatory mechanisms. Obesity can contribute to the development of insulin resistance and hyperinsulinemia, which can directly or indirectly influence the development of fibroids by promoting the proliferation of myometrial smooth muscle cells and increasing circulating levels of ovarian hormones.

Predictors of uterine fibroids development in women outside and during pregnancy

Predictors of uterine fibroids development in women outside and during pregnancy

FRI414 Association Between Uterine Leiomyoma Prevalence And Metabolic Syndrome In A Reproductive Aged Latina/Latinx Population

Abstract Disclosure: E.L. Ferrell: None. S. Schon: None. L. Jiang: None. F. Valbuena: None. E. Manuel: None. M. Castillo-Mackenzie: None. M. Carnethon: None. D.D. Baird: None. L. Neff: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. E.E. Marsh: Consulting Fee; Self; Pfizer, Inc., Myovant Sciences. Objectives: Uterine leiomyomas, commonly known as fibroids, are benign tumors in the wall of the uterus that affect approximately 30% of females by the age of 35, and 70% of females by the age of 50. Greater fibroid prevalence has been observed in certain cohorts, with some studies reporting &amp;gt; 85% prevalence in African American women by the age of 50. Increasing evidence suggests that cardiometabolic risk factors contribute to uterine fibroid development. Few studies have assessed either the prevalence of fibroids or their relationship with Metabolic Syndrome (MetS) in the Latina/Latinx population. The objective of this study was to assess the relationship between MetS and fibroid prevalence in a large cohort of Latina/Latinx females. Materials &amp; Methods: This is a cross-sectional analysis of data collected as part of a prospective longitudinal cohort study. The Environment, Leiomyomas, Latinas, and Adiposity Study (ELLAS) follows 707 Latina women over a 4-year period. All participants in this study were between the ages of 21-50 at the time of enrollment. Demographic and baseline information was collected by trained bilingual study staff. Anthropometric measurements were performed, and fasting blood samples were collected. Participants underwent a baseline pelvic ultrasound to assess for the presence of fibroids. MetS diagnosis was based on the 2005 AHA/NHLBI criteria. The association between MetS and fibroids were assessed as categorical variables. Statistical associations were determined using chi-squared tests and logistic regression. Results: Of the 707 participants enrolled in ELLAS, 621 completed the first study visit, and data from the criteria used to diagnose MetS were available from 590 participants. Of those 590, 578 participants completed ultrasound evaluation for fibroids and were included in final analysis. The mean age was 37.4±6.95 years and the mean BMI was 30.1±6.76 kg/m2. A total of 143 participants met criteria for MetS (24.7%). Prevalence of MetS was positively correlated with age. The prevalence of fibroids in this Latina population was 10.7%. There was no statistically significant association between MetS and the presence of fibroids (p value &amp;gt;0.05). Conclusion: Among a large cohort of Latinx females, MetS was not significantly associated with fibroids. The prevalence of fibroids in this population was lower than observed in other populations, suggesting a possible protective factor yet to be identified amongst Latinx females. Given the low prevalence, we were likely underpowered to detect an association. Further research is needed to determine the relationship between cardiovascular, metabolic, and reproductive outcomes in this understudied population. Presentation: Friday, June 16, 2023

Serum Calcium and Magnesium Levels in Women with Uterine Fibroids in Southwest Nigeria: a Cross-sectional Study.

Studies have suggested the potential roles of serum macronutrients such as calcium and magnesium in the development of uterine fibroids. The primary objective was to assess the association between serum magnesium and calcium levels and the prevalence of uterine fibroids in women of reproductive age. A cross-sectional study of 194 parity-matched women with or without a sonographic diagnosis of uterine fibroids enrolled at a university teaching hospital in Lagos, Southwest Nigeria. Participants' sociodemographic, ultrasound, and anthropometric information as well as the estimated serum levels of calcium and magnesium were collected for statistical analyses. This study found significant negative associations between low serum calcium levels and uterine fibroids (adjusted odds ratio = 0.06), uterine size, and the number of fibroid nodules. However, no significant association was observed between serum magnesium levels and uterine fibroids. This study found significant inverse associations between low serum calcium levels and uterine fibroids, uterine size, and the number of fibroid nodules.

TGFβ signaling links early life endocrine-disrupting chemicals exposure to suppression of nucleotide excision repair in rat myometrial stem cells

Environmental exposure to endocrine-disrupting chemicals (EDCs) is linked to the development of uterine fibroids (UFs) in women. UFs, non-cancerous tumors, are thought to originate from abnormal myometrial stem cells (MMSCs). Defective DNA repair capacity may contribute to the emergence of mutations that promote tumor growth. The multifunctional cytokine TGFβ1 is associated with UF progression and DNA damage repair pathways. To investigate the impact of EDC exposure on TGFβ1 and nucleotide excision repair (NER) pathways, we isolated MMSCs from 5-month-old Eker rats exposed neonatally to diethylstilbestrol (DES), an EDC, or to vehicle (VEH). EDC-MMSCs exhibited overactivated TGFβ1 signaling and reduced mRNA and protein levels of NER pathway components compared to VEH-MMSCs. EDC-MMSCs also demonstrated impaired NER capacity. Exposing VEH-MMSCs to TGFβ1 decreased NER capacity while inhibiting TGFβ signaling in EDC-MMSCs restored it. RNA-seq analysis and further validation revealed decreased expression of Uvrag, a tumor suppressor gene involved in DNA damage recognition, in VEH-MMSCs treated with TGFβ1, but increased expression in EDC-MMSCs after TGFβ signaling inhibition. Overall, we demonstrated that the overactivation of the TGFβ pathway links early life exposure to EDCs with impaired NER capacity, which would lead to increased genetic instability, arise of mutations, and fibroid tumorigenesis. We demonstrated that the overactivation of the TGFβ pathway links early life exposure to EDCs with impaired NER capacity, which would lead to increased fibroid incidence.

The Biological Effects of Vitamin D on the Development of Uterine Fibroids: A Literature Review

Uterine Fibroids (UFs), also known as uterineleiomyomas or myomas, are benign tumors derivedfrom smooth muscle tissue. Vitamin D deficiency is oneof the many factors involved in the development andgrowth of UFs. Many studies have shown that vitamin Dsupplementation decreases the size of fibroids despitea poorly understood pathogenesis. The activity ofvitamin D against UF cells has mainly been supportedby various in vitro and in vivo studies. For this review,we conducted in-depth research of published literatureon vitamin D's biological and pathophysiological effectson UFs. We searched on Google Scholar and PubMedusing common keywords and selected 23 studies fromthe search results. The literature chosen from the pastten years was read and analyzed thoroughly. However,because of the limited research on the effects of vitaminD on UFs and the different inclusion criteria, the clinicalefficacy of vitamin D on women with UFs remainsunclear. More extensive, well-organized studies on thespecific effects of vitamin D on the growth of UFs wouldprove efficacious in establishing treatments.

Pathways of Hypoxia-Inducible Factor (HIF) in the Orchestration of Uterine Fibroids Development.

Uterine fibroids (UF) are common benign tumors in women. The course of UF is associated with troubling symptoms and the development of infertility and pregnancy pathology. Surgical treatment even implies hysterectomy, while pharmacological interventions are modestly effective. Classically, hypoxic metabolism is considered a hallmark of malignant tumor. However, the role of hypoxia-induced factor (HIF) is significant in benign tumors as well. Herein, we briefly review the basic biology of HIF-family proteins, outlining their possible roles in UF. Apart from theoretical justifications, we summarized 15 studies reporting increased expression of HIFs and downstream factors in UF samples. Altogether, data suggest that increased expression of the HIF-protein and altered expression of its dependent genes are presumed to be the factors leading to UF development. Thus, even without being a malignant tumor, UF is characterized by the strong involvement of HIF. This novel insight may give rise to further research in the direction of finding new prognostic markers and effective medicines against UF.

Uterine Fibroids: Retrospective Study with Analysis of Different Risk Factors

Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids.

Beta blockers reduce uterine fibroid incidence in hypertensive women

ObjectiveIs prior beta blocker (BB) use associated with reduced odds of the clinical incidence of leiomyomas? What is known alreadyIn-vitro and in-vivo evidence has supported the role of beta receptor blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association. Study design, size, durationA nested case-control study was conducted in a population of women aged 18–65 with arterial hypertension (n = 699,966). Cases (n = 18,918) with a leiomyoma diagnosis were matched to controls (n = 681,048) with no such diagnosis at a 1:36 ratio by age and region of origin within the United States. Participants/materials, setting, methodsThis population was assembled from the Truven Health MarketScan® Research Database, which includes health insurance claims from January 1st, 2012 to December 31st, 2017. Prior use of BB wasdetermined fromoutpatient drug claims and leiomyoma development was indicated by a first-time diagnosis code. We conducted a conditional logistic regression to determine the odds of uterine fibroid development in women with prior use of BB compared to women with no such history. We then conducted subset analyses, stratifying the women by age group and by type of BB. ResultsWomen on a BB experienced 15% reduced odds of developing clinically recognized leiomyoma compared to non-users (OR 0.85, 95% CI 0.76–0.94). This association was significant for the 30–39 age group (OR 0.61, 95% CI 0.40–0.93) but no other age group. Of the BBs, propranolol (OR 0.58, 95% CI 0.36–95) demonstrated a significant association with reduced leiomyoma incidence and metoprolol (OR 0.82, 95% CI 0.70–0.97) was associated with lower uterine fibroid incidence after adjustment for comorbidities. ConclusionsHypertensive women with prior BB use experienced reduced odds of developing clinically recognized leiomyoma compared to non-users. A key predisposing risk factor for uterine leiomyoma is elevated blood pressure. Thus, the results of this analysis may have clinical relevance to women with hypertension, as the use of this drug may introduce a dual benefit of managing hypertension as well as curbing an increased risk of leiomyomas.

Search for key genes, key signaling pathways, and immune cell infiltration in uterine fibroids by bioinformatics analysis.

Uterine fibroids grow in the myometrium and are benign tumors. The etiology and molecular mechanism are not fully understood. Here, we hope to study the potential pathogenesis of uterine fibroids by bioinformatics. Our aim is to search for the key genes, signaling pathways and immune infiltration about the development of uterine fibroids. The GSE593 expression profile was downloaded from the Gene Expression Omnibus database, which contains 10 samples, including 5 uterine fibroids samples and 5 normal controls. Bioinformatics methods were used to find differentially expressed genes (DEGs) in tissues and further analyze the DEGs. R (version 4.2.1) software was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis of DEGs in uterine leiomyoma tissues and normal control. STRING database was used to generate protein-protein interaction (PPI) networks of key genes. Then, CIBERSORT was used to assess the infiltration of immune cells in uterine fibroids. A total of 834 DEGs were identified, of which 465 were up-regulated and 369 were down-regulated. GO andKEGG pathway analysis showed that the DEGs were mainly concentrated in extracellular matrix and cytokine related signaling pathways. We identified 30 key genes in DEGs from the PPI network. There were some differences in infiltration immunity between the 2 tissues. This study indicated that screening key genes, signaling pathways and immune infiltration by comprehensive bioinformatics analysis is helpful to understand the molecular mechanism of uterine fibroids and provide new insights into understanding the molecular mechanism.

Keloids, hypertrophic scars, and uterine fibroid development: a prospective ultrasound study of Black and African American women

To examine the association between keloids, hypertrophic scars, and uterine fibroid incidence as well as growth. Both keloids and fibroids are fibroproliferative conditions that have been reported to be more prevalent among Blacks than Whites, and they share similar fibrotic tissue structures, including extracellular matrix composition, gene expression, and protein profiles. We hypothesized that women with a history of keloids would have greater uterine fibroid development. A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds to detect and measure fibroids ≥0.5 cm in diameter, assess the history of keloid and hypertrophic scars, and update covariates. Detroit, Michigan area. A total of 1,610 self-identified Black and/or African American women aged 23-35 years at enrollment without a previous clinical diagnosis of fibroids. Keloids (raised scars that grow beyond the margins of the original injury) and hypertrophic scars (raised scars that stay within the bounds of the original injury). Because of the difficulties in distinguishing keloids and hypertrophic scars, we separately examined the history of keloids and the history of either keloids or hypertrophic scars (any abnormal scarring) and their associations with fibroid incidence and growth. Fibroid incidence (new fibroid after a fibroid-free ultrasound at enrollment) was assessed using Cox proportional-hazards regression. Fibroid growth was assessed using linear mixed models. The estimates for the change in log volume per 18 months were converted to the estimated percentage difference in volume for scarring vs. no-scarring. Both incidence and growth models were adjusted for time-varying demographic, reproductive, and anthropometric factors. Of the 1,230 fibroid-free participants, 199 (16%) reported ever having keloids, 578 (47%) reported keloids or hypertrophic scars, and 293 (24%) developed incident fibroids. Neither keloids (adjusted hazard ratio = 1.04; 95% confidence interval: 0.77, 1.40) nor any abnormal scarring (adjusted hazard ratio = 1.10; 95% confidence interval: 0.88, 1.38) were associated with fibroid incidence. Fibroid growth differed little by scarring status. Despite molecular similarities, self-reported keloid and hypertrophic scars did not show an association with fibroid development. Future research may benefit from the examination of dermatologist-confirmed keloids or hypertrophic scars; however, our data suggest little shared susceptibility for these 2 types of fibrotic conditions.

Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.

In the last few decades, our understanding of the complex pathobiology of uterine fibroid development has grown. While previously believed to be a purely neoplastic entity, we now understand that uterine fibroids possess different and equally important aspects of their genesis. An increasing body of evidence suggests that oxidative stress, the imbalance between pro- and antioxidants, is an important factor in fibroid development. Oxidative stress is controlled by multiple, interconnecting cascades, including angiogenesis, hypoxia, and dietary factors. Oxidative stress in turn influences fibroid development through genetic, epigenetic, and profibrotic mechanisms. This unique aspect of fibroid pathobiology has introduced several clinical implications, both diagnostic and therapeutic, that can aid us in managing these debilitating tumors by using biomarkers as well as dietary and pharmaceutical antioxidants for diagnosis and treatment. This review strives to summarize and add to the current evidence revealing the relationship between oxidative stress and uterine fibroids by elucidating the proposed mechanisms and clinical implications.