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Taiwanese Journal of Obstetrics &... Mar 2020Anomalies in the müllerian ducts are congenital alterations with more prevalence than it is imagined, varying from 0.5 to 6.7% in the general population and up to 16.7%... (Review)
Review
Anomalies in the müllerian ducts are congenital alterations with more prevalence than it is imagined, varying from 0.5 to 6.7% in the general population and up to 16.7% in women with recurrent miscarriage. The main findings are primary amenorrhea, dysmenorrhea, pelvic pain, endometriosis, sexual difficulties and low self-esteem. The major impact on the quality of life in women stricken by these problems justifies this study, whose objective is to analyze their most important aspects such as etiopathogeny, classification, diagnostic methods and proposed treatments. The research was performed on the Medline-PubMed database from 1904 to 2018. The American Fertility Society, European Society of Human Reproduction and Embryology, and the European Society of Gynaecological Endoscopy classify malformations as: Class 1/U5bC4V4: agenesis or hypoplasia of uterus and vagina; Class 1/U5aC4V4: cervical hypoplasia, associated with total or partial vaginal agenesis; Class 2/U4: unicornuate uterus; Class 3/U3bC2V1 or Class3/U3bC2V2: uterus didelphys; Class 4/U3C0: bicornuate uterus; Class 5/U2: septate uterus; Class 6: arcuate uterus; Class 7/U1: induced by diethylstilbestrol, represented by a T-shaped uterus; and V3: transverse vaginal septum. The diagnostic methods are the two-dimensional or three-dimensional ultrasound, MRI, hysterosalpingo-contrast-sonography, X-ray hysterosalpingography, hysteroscopy and laparoscopy. Some müllerian malformations are healed with surgery and/or self-dilatation. For vaginal agenesis, dilatation by Frank technique shows good results while malformations with obstruction of the menstrual flow need to be rapidly treated by surgery.
Topics: Adult; Congenital Abnormalities; Dysmenorrhea; Endometriosis; Female; Humans; Hysterosalpingography; Hysteroscopy; Laparoscopy; Magnetic Resonance Imaging; Mullerian Ducts; Pelvic Pain; Pregnancy; Sexual Dysfunction, Physiological; Ultrasonography; Urogenital Abnormalities; Uterus; Vagina
PubMed: 32127135
DOI: 10.1016/j.tjog.2020.01.003 -
Current Obesity Reports Mar 2017The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure.
RECENT FINDINGS
Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.
Topics: Adipocytes; Adipogenesis; Animals; Appetite; Endocrine Disruptors; Endocrine System Diseases; Female; Food Preferences; Health Status; Humans; Mice, Obese; Obesity; Organic Chemicals; PPAR gamma; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Aryl Hydrocarbon; Receptors, Steroid; Risk Assessment; Satiation
PubMed: 28205155
DOI: 10.1007/s13679-017-0240-4 -
Nature Reviews. Endocrinology Jan 2020Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including... (Review)
Review
Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.
Topics: Animals; Consensus; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Humans; Receptors, Corticotropin
PubMed: 31719706
DOI: 10.1038/s41574-019-0273-8 -
JBRA Assisted Reproduction Apr 2019This review aimed to look into agents and mechanisms characterized as endocrine disrupting chemicals (EDCs). These agents are known to cause several harmful effects to... (Review)
Review
This review aimed to look into agents and mechanisms characterized as endocrine disrupting chemicals (EDCs). These agents are known to cause several harmful effects to the reproductive system of women and wildlife. There is a wide range of chemicals, developed for commercial use mainly in agriculture, which may cause endocrine disruption. Numerous studies show evidence of environmental contamination. However, no one is being held liable for the damages. The most important potentially harmful agents are identified and described, along with the different effects they have on the female genital area. Brazil is a large consumer of pesticides and others chemicals that may interfere with a normal women's life. We analyzed and described the mode of action and the impacts of different EDCs (bisphenols, phthalates, atrazine, polychlorinated and polybrominated biphenyls, DDT-dichlorodiphenyltrichloroethane; DDE-dichlorodiphenyldichloroethylene; DDD-dichlorodiphenyldichloroethane; and DES-diethylstilbestrol) on the genital area, ovarian steroidogenesis, polycystic ovary syndrome, endometriosis, the structure of the uterus and the vagina, and on the formation of leiomyomas.
Topics: Endocrine Disruptors; Environmental Exposure; Female; Genital Diseases, Male; Hazardous Substances; Humans; Male; Ovary; Reproductive Health
PubMed: 30875185
DOI: 10.5935/1518-0557.20190016 -
Frontiers in Endocrinology 2022It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and... (Review)
Review
It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in exposed children (n=1,612), and a French cohort study (n=1,002 DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment ( and ). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.
Topics: Child; Humans; Female; Cohort Studies; Endocrine Disruptors; Epigenomics; Mothers
PubMed: 36479217
DOI: 10.3389/fendo.2022.1034959 -
Journal of Translational Medicine Aug 2023Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished.
BACKGROUND
Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished.
METHODS
Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran's Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses.
RESULTS
The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, P = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, P = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, P = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive-compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis.
CONCLUSIONS
In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders.
Topics: Humans; Depressive Disorder, Major; Autism Spectrum Disorder; Genome-Wide Association Study; Mendelian Randomization Analysis; Mental Disorders; 3',5'-Cyclic-AMP Phosphodiesterases
PubMed: 37605207
DOI: 10.1186/s12967-023-04368-0 -
Fertility and Sterility Sep 2016Uterine fibroids are the most frequent gynecologic tumor, affecting 70% to 80% of women over their lifetime. Although these tumors are benign, they can cause significant... (Review)
Review
Uterine fibroids are the most frequent gynecologic tumor, affecting 70% to 80% of women over their lifetime. Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy. Many risk factors for these tumors have been identified, including environmental exposures to endocrine-disrupting chemicals (EDCs) such as genistein and diethylstilbestrol. Uterine development may be a particularly sensitive window to environmental exposures, as some perinatal EDC exposures have been shown to increase tumorigenesis in both rodent models and human epidemiologic studies. The mechanisms by which EDC exposures may increase tumorigenesis are still being elucidated, but epigenetic reprogramming of the developing uterus is an emerging hypothesis. Given the remarkably high incidence of uterine fibroids and their significant impact on women's health, understanding more about how prenatal exposures to EDCs (and other environmental agents) may increase fibroid risk could be key to developing prevention and treatment strategies in the future.
Topics: Animals; Biomarkers, Tumor; Cellular Reprogramming; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Female; Gene Expression Regulation, Developmental; Humans; Leiomyoma; Neoplastic Stem Cells; Risk Assessment; Risk Factors; Uterine Neoplasms
PubMed: 27553264
DOI: 10.1016/j.fertnstert.2016.08.023 -
Cellular Signalling Aug 2023Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyse the intracellular second messengers cAMP and cGMP to their inactive forms 5'AMP... (Review)
Review
Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyse the intracellular second messengers cAMP and cGMP to their inactive forms 5'AMP and 5'GMP. Some members of the PDE family display specificity towards a single cyclic nucleotide messenger, and PDE4, PDE7, and PDE8 specifically hydrolyse cAMP. While the role of PDE4 and its use as a therapeutic target have been well studied, less is known about PDE7 and PDE8. This review aims to collate the present knowledge on human PDE7 and outline its potential use as a therapeutic target. Human PDE7 exists as two isoforms PDE7A and PDE7B that display different expression patterns but are predominantly found in the central nervous system, immune cells, and lymphoid tissue. As a result, PDE7 is thought to play a role in T cell activation and proliferation, inflammation, and regulate several physiological processes in the central nervous system, such as neurogenesis, synaptogenesis, and long-term memory formation. Increased expression and activity of PDE7 has been detected in several disease states, including neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's disease, autoimmune diseases such as multiple sclerosis and COPD, and several types of cancer. Early studies have shown that administration of PDE7 inhibitors may ameliorate the clinical state of these diseases. Targeting PDE7 may therefore provide a novel therapeutic strategy for targeting a broad range of disease and possibly provide a complementary alternative to inhibitors of other cAMP-selective PDEs, such as PDE4, which are severely limited by their side-effects.
Topics: Humans; Cyclic Nucleotide Phosphodiesterases, Type 7; Phosphodiesterase Inhibitors; 3',5'-Cyclic-AMP Phosphodiesterases; Nucleotides, Cyclic
PubMed: 37120115
DOI: 10.1016/j.cellsig.2023.110689