1 1114 123 COMMONALITIES AND DISPARITIES BETWEEN ENDOMETRIOSIS AND CHRONIC ENDOMETRITIS: THERAPEUTIC POTENTIAL OF NOVEL ANTIBIOTIC TREATMENT STRATEGY AGAINST ECTOPIC ENDOMETRIUM. CHRONIC ENDOMETRITIS (CE) IS A LOCAL MUCOSAL INFLAMMATORY DISORDER OF THE UTERINE LINING, WHICH IS HISTOPATHOLOGICALLY RECOGNIZED AS THE UNUSUAL INFILTRATION OF CD138(+) PLASMACYTES INTO THE ENDOMETRIAL STROMAL COMPARTMENT. ACCUMULATING BODY OF RESEARCH DOCUMENTED THAT CE IS ASSOCIATED WITH FEMALE INFERTILITY AND SEVERAL OBSTETRIC/NEONATAL COMPLICATIONS. THE MAJOR CAUSE OF CE IS THOUGHT TO BE INTRAUTERINE INFECTION REPRESENTED BY COMMON BACTERIA (ESCHERICHIA COLI, ENTEROCOCCUS FAECALIS, STREPTOCOCCUS, AND STAPHYLOCOCCUS), MYCOPLASMA/UREAPLASMA, AND MYCOBACTERIUM. ADDITIONALLY, LOCAL DYSBIOSIS IN THE FEMALE REPRODUCTIVE TRACT MAY BE INVOLVED IN THE ONSET AND DEVELOPMENT OF CE. ANTIBIOTIC TREATMENTS AGAINST THESE MICROORGANISMS ARE EFFECTIVE IN THE ELIMINATION OF ENDOMETRIAL STROMAL PLASMACYTES IN THE AFFECTED PATIENTS. MEANWHILE, ENDOMETRIOSIS IS A COMMON FEMALE REPRODUCTIVE TRACT DISEASE CHARACTERIZED BY ENDOMETRIOTIC TISSUES (ECTOPIC ENDOMETRIUM) GROWING OUTSIDE THE UTERUS AND POTENTIALLY CAUSES CHRONIC PELVIC SYMPTOMS (DYSMENORRHEA, DYSPAREUNIA, DYSCHEZIA, AND DYSURIA), INFERTILITY, AND OVARIAN CANCERS. ENDOMETRIOSIS INVOLVES ENDOCRINOLOGICAL, GENETIC, AND EPIGENETIC FACTORS IN ITS ETIOLOGY AND PATHOGENESIS. RECENT STUDIES FOCUS ON IMMUNOLOGICAL, INFLAMMATORY, AND INFECTIOUS ASPECTS OF ENDOMETRIOSIS AND DEMONSTRATE SEVERAL COMMON CHARACTERISTICS BETWEEN ENDOMETRIOSIS AND CE. THIS REVIEW AIMED TO BETTER UNDERSTAND THE IMMUNOLOGICAL AND MICROBIAL BACKGROUNDS UNDERLYING ENDOMETRIOSIS AND CE AND LOOK INTO THE THERAPEUTIC POTENTIAL OF THE NOVEL ANTIBIOTIC TREATMENT STRATEGY AGAINST ENDOMETRIOSIS IN LIGHT OF ENDOMETRIAL INFECTIOUS DISEASE. 2023 2 1889 32 ENDOMETRIOSIS MALIGNANT TRANSFORMATION: EPIGENETICS AS A PROBABLE MECHANISM IN OVARIAN TUMORIGENESIS. ENDOMETRIOSIS, DEFINED AS THE PRESENCE OF ECTOPIC ENDOMETRIAL GLANDS AND STROMA OUTSIDE THE UTERINE CAVITY, IS A CHRONIC, HORMONE-DEPENDENT GYNECOLOGIC DISEASE AFFECTING MILLIONS OF WOMEN ACROSS THE WORLD, WITH SYMPTOMS INCLUDING CHRONIC PELVIC PAIN, DYSMENORRHEA, DYSPAREUNIA, DYSURIA, AND SUBFERTILITY. IN ADDITION, THERE IS WELL-ESTABLISHED EVIDENCE THAT, ALTHOUGH ENDOMETRIOSIS IS CONSIDERED BENIGN, IT IS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT TRANSFORMATION, WITH THE INVOLVEMENT OF VARIOUS MECHANISMS OF DEVELOPMENT. MORE AND MORE EVIDENCE REVEALS AN IMPORTANT CONTRIBUTION OF EPIGENETIC MODIFICATION NOT ONLY IN ENDOMETRIOSIS BUT ALSO IN MECHANISMS OF ENDOMETRIOSIS MALIGNANT TRANSFORMATION, INCLUDING DNA METHYLATION AND DEMETHYLATION, HISTONE MODIFICATIONS, AND MIRNA ABERRANT EXPRESSIONS. IN THIS PRESENT REVIEW, WE MAINLY SUMMARIZE THE RESEARCH PROGRESS ABOUT THE CURRENT KNOWLEDGE REGARDING THE EPIGENETIC MODIFICATIONS OF THE RELATIONS BETWEEN ENDOMETRIOSIS MALIGNANT TRANSFORMATION AND OVARIAN CANCER IN AN EFFORT TO IDENTIFY SOME RISK FACTORS PROBABLY ASSOCIATED WITH ECTOPIC ENDOMETRIUM TRANSFORMATION. 2018 3 6237 30 THE MAIN THEORIES ON THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A COMPLEX DISEASE, WHICH IS DEFINED BY ABNORMAL GROWTH OF ENDOMETRIAL TISSUE OUTSIDE THE UTERUS. IT AFFECTS ABOUT 10% OF WOMEN OF REPRODUCTIVE AGE ALL OVER THE WORLD. ENDOMETRIOSIS CAUSES SYMPTOMS THAT NOTABLY WORSEN PATIENT'S WELL-BEING-SUCH AS SEVERE PELVIC PAIN, DYSFUNCTION OF THE ORGANS OF PELVIC CAVITY, INFERTILITY AND SECONDARY MENTAL ISSUES. THE DIAGNOSIS OF ENDOMETRIOSIS IS QUITE OFTEN DELAYED BECAUSE OF NONSPECIFIC MANIFESTATIONS. SINCE THE DISEASE WAS DEFINED, SEVERAL DIFFERENT PATHOGENETIC PATHWAYS HAVE BEEN CONSIDERED, INCLUDING RETROGRADE MENSTRUATION, BENIGN METASTASIS, IMMUNE DYSREGULATION, COELOMIC METAPLASIA, HORMONAL DISBALANCE, INVOLVEMENT OF STEM CELLS AND ALTERATIONS IN EPIGENETIC REGULATION, BUT THE TRUE PATHOGENESIS OF ENDOMETRIOSIS REMAINS POORLY UNDERSTOOD. THE KNOWLEDGE OF THE EXACT MECHANISM OF THE ORIGIN AND PROGRESSION OF THIS DISEASE IS SIGNIFICANT FOR THE APPROPRIATE TREATMENT. THEREFORE, THIS REVIEW REPORTS THE MAIN PATHOGENETIC THEORIES OF ENDOMETRIOSIS BASED ON CURRENT STUDIES. 2023 4 2602 35 EPIGENETICS, ENDOMETRIOSIS AND SEX STEROID RECEPTORS: AN UPDATE ON THE EPIGENETIC REGULATORY MECHANISMS OF ESTROGEN AND PROGESTERONE RECEPTORS IN PATIENTS WITH ENDOMETRIOSIS. ENDOMETRIOSIS IS A BENIGN GYNECOLOGICAL DISEASE AFFECTING APPROXIMATELY 10% OF REPRODUCTIVE-AGED WOMEN AND IS DEFINED AS THE PRESENCE OF ENDOMETRIAL GLANDS AND STROMA OUTSIDE THE UTERINE CAVITY. ENDOMETRIOSIS CAN CAUSE A VARIETY OF HEALTH PROBLEMS, FROM PELVIC DISCOMFORT TO CATAMENIAL PNEUMOTHORAX, BUT IT'S MAINLY LINKED WITH SEVERE AND CHRONIC PELVIC PAIN, DYSMENORRHEA, AND DEEP DYSPAREUNIA, AS WELL AS REPRODUCTIVE ISSUES. THE PATHOGENESIS OF ENDOMETRIOSIS INVOLVES AN ENDOCRINE DYSFUNCTION, WITH ESTROGEN DEPENDENCY AND PROGESTERONE RESISTANCE, AND INFLAMMATORY MECHANISM ACTIVATION, TOGETHER WITH IMPAIRED CELL PROLIFERATION AND NEUROANGIOGENESIS. THE PRESENT CHAPTER AIMS TO DISCUSS THE MAIN EPIGENETIC MECHANISMS RELATED TO ESTROGEN RECEPTORS (ERS) AND PROGESTERONE RECEPTORS (PRS) IN PATIENTS WITH ENDOMETRIOSIS. THERE ARE NUMEROUS EPIGENETIC MECHANISMS PARTICIPATING IN ENDOMETRIOSIS, REGULATING THE EXPRESSION OF THE GENES ENCODING THESE RECEPTORS BOTH INDIRECTLY, THROUGH THE REGULATION OF TRANSCRIPTION FACTORS, AND DIRECTLY, THROUGH DNA METHYLATION, HISTONE MODIFICATIONS, MICRO RNAS AND LONG NONCODING RNAS. THIS REPRESENTS AN OPEN FIELD OF INVESTIGATION, WHICH MAY LEAD TO IMPORTANT CLINICAL IMPLICATIONS SUCH AS THE DEVELOPMENT OF EPIGENETIC DRUGS FOR THE TREATMENT OF ENDOMETRIOSIS AND THE IDENTIFICATION OF SPECIFIC AND EARLY BIOMARKERS FOR THE DISEASE. 2023 5 4956 34 PATHOGENESIS OF ENDOMETRIOSIS: FOCUS ON ADENOGENESIS-RELATED FACTORS. ENDOMETRIOSIS CAN BE DEFINED AS THE PRESENCE OF THE ENDOMETRIUM OUTSIDE THE UTERINE CAVITY. IT AFFECTS APPROXIMATELY 10% OF WOMEN OF REPRODUCTIVE AGE AND CAUSES INFERTILITY, CHRONIC PAIN, AND DETERIORATION OF THE QUALITY OF LIFE. SINCE THE IDENTIFICATION OF THE DISEASE, VARIOUS PATHOGENETIC MECHANISMS HAVE BEEN PROPOSED, SUCH AS RETROGRADE MENSTRUATION, COELOMIC METAPLASIA, HORMONAL IMBALANCE, STEM CELL INVOLVEMENT, AND ALTERATIONS IN EPIGENETIC REGULATION. HOWEVER, THE UNDERLYING PATHOGENESIS OF ENDOMETRIOSIS REMAINS INADEQUATELY UNDERSTOOD. ELUCIDATION OF THE PRECISE MECHANISM OF THE DEVELOPMENT AND PROGRESSION OF ENDOMETRIOSIS IS CRUCIAL FOR EFFECTIVE TREATMENT. THIS REVIEW PRESENTS THE MAJOR PATHOGENETIC THEORIES OF ENDOMETRIOSIS BASED ON CURRENT RESEARCH STUDIES WITH A MAJOR FOCUS ON THE POTENTIAL ROLE OF UTERINE FACTORS. 2023 6 4435 42 MOLECULAR DYSREGULATIONS UNDERLYING THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A CRIPPLING DISEASE CHARACTERIZED BY THE PRESENCE OF ENDOMETRIUM-LIKE TISSUE OR SCAR OUTSIDE THE UTERINE CAVITY, COMMONLY CONFINED TO THE PERITONEAL AND SEROSAL SURFACES OF THE PELVIC ORGANS. 10-15% OF WOMEN IN REPRODUCTIVE AGE ARE ESTIMATED TO BE AFFECTED BY ENDOMETRIOSIS. MOST OF THESE PATIENTS PRESENT WITH INFERTILITY AND SUFFER FROM PELVIC PAIN. THE BENIGN DISEASE RARELY PROGRESSES TO MALIGNANCY. REGARDLESS OF ITS HIGH PREVALENCE, THE PATHOGENESIS OF THE DISEASE IS NOT FULLY UNDERSTOOD. TREATMENT OPTIONS FOR ENDOMETRIOSIS ARE LIMITED AND ARE OFTEN BASED ON A SYMPTOMATIC APPROACH. THE UNAVAILABILITY OF PROPER DIAGNOSTIC APPROACHES, FEWER THERAPEUTIC OPTIONS, AND SPARSE UNDERSTANDING OF MOLECULAR ALTERATIONS ARE RESPONSIBLE FOR THE CONTINUED DISEASE BURDEN. EXPLORING THE MOLECULAR ELEMENTS CAUSING THE PATHOGENESIS OF ENDOMETRIOSIS MAY LEAD TO A NUMBER OF BREAKTHROUGHS IN THE TREATMENT OF THE ILLNESS, SUCH AS THE DISCOVERY OF NEW BIOMARKERS FOR DIAGNOSIS AND THERAPEUTIC TARGETS THAT CAN BE A GUIDE TO BETTER PROGNOSIS AND REDUCED RECURRENCE. THE GOAL OF THIS REVIEW IS TO PROVIDE THE READER A CRITICAL UNDERSTANDING OF THE DISEASE BY SUMMARIZING THE GENETIC, IMMUNOLOGICAL, HORMONAL, AND EPIGENETIC DEREGULATIONS THAT SUPPORT THE MOLECULAR BASIS FOR DEVELOPMENT OF ENDOMETRIOTIC CYST, WITH A SPECIAL FOCUS ON THE STUDY MODELS NEEDED TO ANALYZE THESE CHANGES IN THE ENDOMETRIOTIC MICROENVIRONMENT. 2021 7 4957 32 PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY. OBJECTIVE: TO STUDY THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS. DESIGN: OVERVIEW OF OBSERVATIONS ON ENDOMETRIOSIS. SETTING: NOT APPLICABLE. PATIENT(S): NONE. INTERVENTIONS(S): NONE. MAIN OUTCOME MEASURE(S): THE HYPOTHESIS IS COMPATIBLE WITH ALL OBSERVATIONS. RESULT(S): ENDOMETRIOSIS, ENDOMETRIUM-LIKE TISSUE OUTSIDE THE UTERUS, HAS A VARIABLE MACROSCOPIC APPEARANCE AND A POORLY UNDERSTOOD NATURAL HISTORY. IT IS A HEREDITARY AND HETEROGENEOUS DISEASE WITH MANY BIOCHEMICAL CHANGES IN THE LESIONS, WHICH ARE CLONAL IN ORIGIN. IT IS ASSOCIATED WITH PAIN, INFERTILITY, ADENOMYOSIS, AND CHANGES IN THE JUNCTIONAL ZONE, PLACENTATION, IMMUNOLOGY, PLASMA, PERITONEAL FLUID, AND CHRONIC INFLAMMATION OF THE PERITONEAL CAVITY. THE SAMPSON HYPOTHESIS OF IMPLANTED ENDOMETRIAL CELLS FOLLOWING RETROGRADE MENSTRUATION, ANGIOGENIC SPREAD, LYMPHOGENIC SPREAD, OR THE METAPLASIA THEORY CANNOT EXPLAIN ALL OBSERVATIONS IF METAPLASIA IS DEFINED AS CELLS WITH REVERSIBLE CHANGES AND AN ABNORMAL BEHAVIOR/MORPHOLOGY DUE TO THE ABNORMAL ENVIRONMENT. WE PROPOSE A POLYGENETIC/POLYEPIGENETIC MECHANISM. THE SET OF GENETIC AND EPIGENETIC INCIDENTS TRANSMITTED AT BIRTH COULD EXPLAIN THE HEREDITARY ASPECTS, THE PREDISPOSITION, AND THE ENDOMETRIOSIS-ASSOCIATED CHANGES IN THE ENDOMETRIUM, IMMUNOLOGY, AND PLACENTATION. TO DEVELOP TYPICAL, CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS, A VARIABLE SERIES OF ADDITIONAL TRANSMISSIBLE GENETIC AND EPIGENETIC INCIDENTS ARE REQUIRED TO OCCUR IN A CELL WHICH MAY VARY FROM ENDOMETRIAL TO STEM CELLS. SUBTLE LESIONS ARE VIEWED AS ENDOMETRIUM IN A DIFFERENT ENVIRONMENT UNTIL ADDITIONAL INCIDENTS OCCUR. TYPICAL CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS ARE HETEROGENEOUS AND REPRESENT THREE DIFFERENT DISEASES. CONCLUSION(S): THE GENETIC EPIGENETIC THEORY IS COMPATIBLE WITH ALL OBSERVATIONS ON ENDOMETRIOSIS. IMPLICATIONS FOR TREATMENT AND PREVENTION ARE DISCUSSED. 2019 8 5378 26 RECENT INSIGHTS ON THE GENETICS AND EPIGENETICS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A GYNECOLOGIC DISEASE AFFECTING UP TO 10% OF THE WOMEN AND A MAJOR CAUSE OF PAIN AND INFERTILITY. IT IS CHARACTERIZED BY THE IMPLANTATION OF FUNCTIONAL ENDOMETRIAL TISSUE AT ECTOPIC POSITIONS GENERALLY WITHIN THE PERITONEUM. THIS COMPLEX DISEASE HAS AN IMPORTANT GENETIC COMPONENT WITH A HERITABILITY ESTIMATED AT AROUND 50%. THIS REVIEW AIMS AT PROVIDING RECENT INSIGHTS INTO THE GENETIC BASES OF ENDOMETRIOSIS, AND PRESENTS A DETAILED OVERVIEW OF EVIDENCE OF EPIGENETIC ALTERATIONS SPECIFIC TO THIS DISEASE. IN THE FUTURE, THESE ALTERATIONS MAY CONSTITUTE THERAPEUTIC TARGETS FOR PHARMACOLOGICAL COMPOUNDS ABLE TO MODIFY THE EPIGENETIC CODE. 2017 9 5892 37 SYSTEMS GENETICS VIEW OF ENDOMETRIOSIS: A COMMON COMPLEX DISORDER. ENDOMETRIOSIS IS A CONDITION IN WHICH CELLS DERIVED FROM THE ENDOMETRIUM GROW OUTSIDE THE UTERUS, E.G. IN THE PERITONEUM (EXTERNAL GENITAL ENDOMETRIOSIS). AS THESE CELLS ARE UNDER THE INFLUENCE OF FEMALE HORMONES, MAJOR SYMPTOMS OF ENDOMETRIOSIS ARE PAIN, ESPECIALLY DURING THE CYCLE, AND INFERTILITY. NUMEROUS HYPOTHESES FOR THE FORMATION OF ENDOMETRIOSIS CAN BE FOUND IN THE LITERATURE, BUT THERE IS GROWING EVIDENCE OF SERIOUS GENETIC CONTRIBUTIONS TO ENDOMETRIOSIS SUSCEPTIBILITY. THE INVOLVEMENT OF GENES, STEROID HORMONE METABOLISM, IMMUNOLOGICAL REACTIONS, RECEPTOR FORMATION, INFLAMMATION, PROLIFERATION, APOPTOSIS, INTERCELLULAR ADHESION, CELL INVASION AND ANGIOGENESIS AS WELL AS GENES REGULATING THE ACTIVITY OF AFOREMENTIONED ENZYMES HAVE BEEN SUGGESTED. SOME MORE RECENTLY SUGGESTED CANDIDATE GENES PICKED UP IN GENOME-WIDE ASSOCIATION STUDIES ARE INVOLVED IN ONCOGENESIS, METAPLASIA OF ENDOMETRIUM CELLS AND PATHWAYS OF EMBRYONIC DEVELOPMENT OF THE FEMALE REPRODUCTIVE SYSTEM. HOWEVER, GENE MUTATIONS PROVEN TO BE CAUSATIVE FOR ENDOMETRIOSIS HAVE NOT BEEN IDENTIFIED SO FAR, EVEN THOUGH THE ABNORMAL EXPRESSION OF CANDIDATE GENES FOR ENDOMETRIOSIS COULD BE PROVOKED BY DIFFERENT EPIGENETIC MODIFICATIONS INCLUDING DNA METHYLATION, HETEROCHROMATIZATION OR INTRODUCTION OF REGULATORY MIRNA. WE HYPOTHESIZE THAT ENDOMETRIOSIS IS INDUCED BY A COMBINATION OF ABNORMAL GENETIC AND/OR EPIGENETIC MUTATIONS: THE LATTER PAVE THE WAY FOR PATHOLOGICAL CHANGES WHICH BECOME IRREVERSIBLE, AND ACCORDING TO THE "EPIGENETIC LANDSCAPE" THEORY, THIS PROCEEDS TO THE TYPICAL CLINICAL MANIFESTATIONS. TWO STAGES IN THE ENDOMETRIOSIS PATHWAY ARE SUGGESTED: (1) INDUCTION OF PRIMARY ENDOMETRIAL CELLS TOWARD ENDOMETRIOSIS, AND (2) IMPLANTATION AND PROGRESSION OF THESE CELLS INTO ENDOMETRIOSIS LESIONS. THE MODEL FAVORS ENDOMETRIOSIS AS AN OUTGROWTH OF PRIMARY CELLS DIFFERENT IN THEIR ORIGIN, CANALIZATION OF PATHOLOGICAL PROCESSES, MANIFESTATION DIVERSITY PROVOKED BY UNIQUE GENETIC BACKGROUND AND EPIGENETIC INFLUENCES, WHICH RESULT IN MANY DIFFERENT CLINICAL FORMS OF THE DISEASE. 2015 10 3003 33 GENETIC, EPIGENETIC AND STEM CELL ALTERATIONS IN ENDOMETRIOSIS: NEW INSIGHTS AND POTENTIAL THERAPEUTIC PERSPECTIVES. HUMAN ENDOMETRIUM IS A HIGHLY DYNAMIC TISSUE, UNDERGOING PERIODIC GROWTH AND REGRESSION AT EACH MENSTRUAL CYCLE. ENDOMETRIOSIS IS A FREQUENT CHRONIC PATHOLOGICAL STATUS CHARACTERIZED BY ENDOMETRIAL TISSUE WITH AN ECTOPIC LOCALIZATION, CAUSING PELVIC PAIN AND INFERTILITY AND A VARIABLE CLINICAL PRESENTATION. IN ADDITION, THERE IS WELL-ESTABLISHED EVIDENCE THAT, ALTHOUGH ENDOMETRIOSIS IS CONSIDERED BENIGN, IT IS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT TRANSFORMATION IN APPROXIMATELY 1.0% OF AFFECTED WOMEN, WITH THE INVOLVEMENT OF MULTIPLE PATHWAYS OF DEVELOPMENT. INCREASING EVIDENCE SUPPORTS A KEY CONTRIBUTION OF DIFFERENT STEM/PROGENITOR CELL POPULATIONS NOT ONLY IN THE CYCLIC REGENERATION OF EUTOPIC ENDOMETRIUM, BUT ALSO IN THE PATHOGENESIS OF AT LEAST SOME TYPES OF ENDOMETRIOSIS. EVIDENCE HAS ARISEN FROM EXPERIMENTS IN ANIMAL MODELS OF DISEASE THROUGH DIFFERENT KINDS OF ASSAYS (INCLUDING CLONOGENICITY, THE LABEL-RETAINING CELL APPROACH, THE ANALYSIS OF UNDIFFERENTIATION MARKERS), AS WELL AS FROM DESCRIPTIVE STUDIES ON ECTOPIC AND EUTOPIC TISSUE SAMPLES HARVESTED FROM AFFECTED WOMEN. CHANGES IN STEM CELL POPULATIONS IN ENDOMETRIOTIC LESIONS ARE ASSOCIATED WITH GENETIC AND EPIGENETIC ALTERATIONS, INCLUDING IMBALANCE OF MIRNA EXPRESSION, HISTONE AND DNA MODIFICATIONS AND CHROMOSOMAL ABERRATIONS. THE PRESENT SHORT REVIEW MAINLY SUMMARIZES THE LATEST OBSERVATIONS CONTRIBUTING TO THE CURRENT KNOWLEDGE REGARDING THE PRESENCE AND THE POTENTIAL CONTRIBUTION OF STEM/PROGENITOR CELLS IN EUTOPIC ENDOMETRIUM AND THE AETIOLOGY OF ENDOMETRIOSIS, TOGETHER WITH A REPORT OF THE MOST RECENTLY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS IN ENDOMETRIOSIS. WE ALSO DESCRIBE THE POTENTIAL ADVANTAGES OF SINGLE CELL MOLECULAR PROFILING IN ENDOMETRIUM AND IN ENDOMETRIOTIC LESIONS. ALL THESE DATA CAN HAVE CLINICAL IMPLICATIONS AND PROVIDE A BASIS FOR NEW POTENTIAL THERAPEUTIC APPLICATIONS. 2014 11 1028 35 CIRCULATING MIRNAS RELATED TO EPITHELIAL-MESENCHYMAL TRANSITIONS (EMT) AS THE NEW MOLECULAR MARKERS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE DEFINED BY THE PRESENCE OF ENDOMETRIAL-LIKE TISSUE FOUND OUTSIDE THE UTERUS, MOST COMMONLY IN THE PERITONEAL CAVITY. ENDOMETRIOSIS LESIONS ARE HETEROGENOUS BUT USUALLY CONTAIN ENDOMETRIAL STROMAL CELLS AND EPITHELIAL GLANDS, IMMUNE CELL INFILTRATES AND ARE VASCULARIZED AND INNERVATED BY NERVES. THE COMPLEX ETIOPATHOGENESIS AND HETEROGENITY OF THE CLINICAL SYMPTOMS, AS WELL AS THE LACK OF A SPECIFIC NON-INVASIVE DIAGNOSTIC BIOMARKERS, UNDERLINE THE NEED FOR MORE ADVANCED DIAGNOSTIC TOOLS. UNFORTUNATELY, THE CONTRIBUTION OF ENVIRONMENTAL, HORMONAL AND IMMUNOLOGICAL FACTORS IN THE DISEASE ETIOLOGY IS INSUFFICIENT, AND THE CONTRIBUTION OF GENETIC/EPIGENETIC FACTORS IS STILL FRAGMENTARY. THEREFORE, THERE IS A NEED FOR MORE FOCUSED STUDY ON THE MOLECULAR MECHANISMS OF ENDOMETRIOSIS AND NON-INVASIVE DIAGNOSTIC MONITORING SYSTEMS. MICRORNAS (MIRNAS) DEMONSTRATE HIGH STABILITY AND TISSUE SPECIFICITY AND PLAY A SIGNIFICANT ROLE IN MODULATING A RANGE OF MOLECULAR PATHWAYS, AND HENCE MAY BE SUITABLE DIAGNOSTIC BIOMARKERS FOR THE ORIGIN AND DEVELOPMENT OF ENDOMETRIOSIS. OF THESE, THE MOST FREQUENTLY STUDIED ARE THOSE RELATED TO ENDOMETRIOSIS, INCLUDING THOSE INVOLVED IN EPITHELIAL-MESENCHYMAL TRANSITION (EMT), WHOSE EXPRESSION IS ALTERED IN PLASMA OR ENDOMETRIOTIC LESION BIOPSIES; HOWEVER, THE RESULTS ARE AMBIGUOUS. SPECIFIC MIRNAS EXPRESSED IN ENDOMETRIOSIS MAY SERVE AS DIAGNOSTICS MARKERS WITH PROGNOSTIC VALUE, AND THEY HAVE BEEN PROPOSED AS MOLECULAR TARGETS FOR TREATMENT. THE AIM OF THIS REVIEW IS TO PRESENT SELECTED MIRNAS ASSOCIATED WITH EMT KNOWN TO HAVE EXPERIMENTALLY CONFIRMED SIGNIFICANCE, AND DISCUSS THEIR UTILITY AS BIOMARKERS IN ENDOMETRIOSIS. 2021 12 3820 30 INTRODUCTION TO PRECLINICAL EVIDENCE FROM ANIMAL MODELS OF ENDOMETRIOSIS. ENDOMETRIOSIS, THE PRESENCE AND GROWTH OF UTERINE ENDOMETRIAL GLANDULAR EPITHELIAL AND STROMA CELLS OUTSIDE THE UTERINE CAVITY, CAUSES PAIN AND INFERTILITY IN WOMEN AND GIRLS OF REPRODUCTIVE AGE. AS RANDOMIZED, DOUBLE-BLINDED, CONTROLLED STUDIES OF ENDOMETRIOSIS IN WOMEN ARE IMPRACTICAL AND AT TIMES ETHICALLY PROHIBITIVE, ANIMAL MODELS FOR ENDOMETRIOSIS AROSE AS AN IMPORTANT ADJUNCT TO GAIN MECHANISTIC INSIGHTS INTO THE ETIOLOGY AND PATHOPHYSIOLOGICAL MECHANISMS OF THIS PERPLEXING DISORDER. A MORE THOROUGH UNDERSTANDING OF ENDOMETRIOSIS IN WOMEN MAY HELP DEVELOP NOVEL NONINVASIVE DIAGNOSTICS, CLASSIFICATION SYSTEMS, THERAPEUTIC REGIMES, AND EVEN PREVENTATIVE METHODS FOR THE MANAGEMENT OF ENDOMETRIOSIS. THIS CHAPTER IS INTENDED TO INTRODUCE A BRIEF HISTORICAL BACKGROUND, BIOLOGICAL AND EPIDEMIOLOGICAL ASPECTS, THE MAJOR SYMPTOMS, THE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS, AND AN EXAMPLE OF AN EPIGENETIC FACTOR OF ENDOMETRIOSIS IN WOMEN. 2020 13 1891 39 ENDOMETRIOSIS. PELVIC ENDOMETRIOSIS IS A COMPLEX SYNDROME CHARACTERIZED BY AN ESTROGEN-DEPENDENT CHRONIC INFLAMMATORY PROCESS THAT AFFECTS PRIMARILY PELVIC TISSUES, INCLUDING THE OVARIES. IT IS CAUSED WHEN SHED ENDOMETRIAL TISSUE TRAVELS RETROGRADE INTO THE LOWER ABDOMINAL CAVITY. ENDOMETRIOSIS IS THE MOST COMMON CAUSE OF CHRONIC PELVIC PAIN IN WOMEN AND IS ASSOCIATED WITH INFERTILITY. THE UNDERLYING PATHOLOGIC MECHANISMS IN THE INTRACAVITARY ENDOMETRIUM AND EXTRAUTERINE ENDOMETRIOTIC TISSUE INVOLVE DEFECTIVELY PROGRAMMED ENDOMETRIAL MESENCHYMAL PROGENITOR/STEM CELLS. ALTHOUGH ENDOMETRIOTIC STROMAL CELLS, WHICH COMPOSE THE BULK OF ENDOMETRIOTIC LESIONS, DO NOT CARRY SOMATIC MUTATIONS, THEY DEMONSTRATE SPECIFIC EPIGENETIC ABNORMALITIES THAT ALTER EXPRESSION OF KEY TRANSCRIPTION FACTORS. FOR EXAMPLE, GATA-BINDING FACTOR-6 OVEREXPRESSION TRANSFORMS AN ENDOMETRIAL STROMAL CELL TO AN ENDOMETRIOTIC PHENOTYPE, AND STEROIDOGENIC FACTOR-1 OVEREXPRESSION CAUSES EXCESSIVE PRODUCTION OF ESTROGEN, WHICH DRIVES INFLAMMATION VIA PATHOLOGICALLY HIGH LEVELS OF ESTROGEN RECEPTOR-BETA. PROGESTERONE RECEPTOR DEFICIENCY CAUSES PROGESTERONE RESISTANCE. POPULATIONS OF ENDOMETRIAL AND ENDOMETRIOTIC EPITHELIAL CELLS ALSO HARBOR MULTIPLE CANCER DRIVER MUTATIONS, SUCH AS KRAS, WHICH MAY BE ASSOCIATED WITH THE ESTABLISHMENT OF PELVIC ENDOMETRIOSIS OR OVARIAN CANCER. IT IS NOT KNOWN HOW INTERACTIONS BETWEEN EPIGENOMICALLY DEFECTIVE STROMAL CELLS AND THE MUTATED GENES IN EPITHELIAL CELLS CONTRIBUTE TO THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS-ASSOCIATED PELVIC PAIN IS MANAGED BY SUPPRESSION OF OVULATORY MENSES AND ESTROGEN PRODUCTION, CYCLOOXYGENASE INHIBITORS, AND SURGICAL REMOVAL OF PELVIC LESIONS, AND IN VITRO FERTILIZATION IS FREQUENTLY USED TO OVERCOME INFERTILITY. ALTHOUGH NOVEL TARGETED TREATMENTS ARE BECOMING AVAILABLE, AS ENDOMETRIOSIS PATHOPHYSIOLOGY IS BETTER UNDERSTOOD, PREVENTIVE APPROACHES SUCH AS LONG-TERM OVULATION SUPPRESSION MAY PLAY A CRITICAL ROLE IN THE FUTURE. 2019 14 2989 40 GENETIC FACTORS INVOLVED IN THE CO?OCCURRENCE OF ENDOMETRIOSIS WITH ANKYLOSING SPONDYLITIS (REVIEW). PREVIOUS RESEARCH HAS REVEALED AN ASSOCIATION BETWEEN ENDOMETRIOSIS AND VARIOUS AUTOIMMUNE DISEASES, WHILE RECENT DATA SUGGEST, FOR THE FIRST TIME, AN ASSOCIATION BETWEEN ENDOMETRIOSIS AND THE RISK OF DEVELOPING ANKYLOSING SPONDYLITIS (AS). AS, THE PROTOTYPE OF SPONDYLOARTHRITIDES DISEASES, IS A SYSTEMIC, CHRONIC, IMMUNE?MEDIATED INFLAMMATORY ARTHRITIS, WHICH PRIMARILY AFFECTS THE SPINE AND SACROILIAC JOINTS, AS WELL AS THE AXIAL SKELETON WITH OR WITHOUT EXTRASPINAL MANIFESTATIONS. AS IS OF POLYGENIC INHERITANCE AND NUMEROUS IMMUNOLOGICALLY RELEVANT GENES CONTRIBUTE TO ITS DEVELOPMENT. ENDOMETRIOSIS IS AN ENIGMATIC, RELATIVELY COMMON, BENIGN, ESTROGEN?DEPENDENT, HETEROGENEOUS GYNECOLOGICAL DISEASE, INFLUENCED BY MULTIPLE GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. IT IS CHARACTERIZED BY THE GROWTH OF ENDOMETRIAL TISSUE OCCURRING IN SITES OTHER THAN THE UTERINE CAVITY, MOST COMMONLY IN THE PELVIC CAVITY, INCLUDING THE OVARIES AND THE UTEROSACRAL LIGAMENTS, AFFECTING UP TO 10% OF THE FEMALE POPULATION OF CHILDBEARING AGE, CAUSING PAIN AND INFERTILITY. THE PRESENT REVIEW DISCUSSES WHETHER A PARTIALLY SHARED GENETIC BACKGROUND MAY EXPLAIN THE CO?OCCURRENCE OF THESE DISORDERS, AS WELL AS POTENTIAL SIMILARITIES REGARDING THE UNDERLYING PATHOGENETIC MECHANISMS AND SPECIFIC MOLECULAR AND CELLULAR PATHWAYS. 2023 15 3005 37 GENETIC, EPIGENETIC, AND STEROIDOGENIC MODULATION MECHANISMS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE, AFFECTING UP TO 10% OF REPRODUCTIVE-AGE WOMEN. THE EXACT CAUSE OF THE DISEASE IS UNKNOWN; HOWEVER, IT IS A HERITABLE CONDITION AFFECTED BY MULTIPLE GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. PREVIOUS STUDIES REPORTED VARIATIONS IN THE EPIGENETIC PATTERNS OF NUMEROUS GENES KNOWN TO BE INVOLVED IN THE ABERRANT MODULATION OF CELL CYCLE STEROIDOGENESIS, ABNORMAL HORMONAL, IMMUNE AND INFLAMMATORY STATUS IN ENDOMETRIOSIS, APOPTOSIS, ADHESION, ANGIOGENESIS, PROLIFERATION, IMMUNE AND INFLAMMATORY PROCESSES, RESPONSE TO HYPOXIA, STEROIDOGENIC PATHWAY AND HORMONE SIGNALING ARE INVOLVED IN THE PATHOGENESIS OF ENDOMETRIOSIS. ACCUMULATING EVIDENCE SUGGEST THAT VARIOUS EPIGENETIC ABERRATIONS MAY CONTRIBUTE TO THE PATHOGENESIS OF ENDOMETRIOSIS. AMONG THEM, DNA METHYLTRANSFERASES, HISTONE DEACETYLATORS, AND NON-CODING MICRORNAS DEMONSTRATE DIFFERENTIAL EXPRESSION WITHIN ENDOMETRIOTIC LESIONS AND IN THE ENDOMETRIUM OF PATIENTS WITH ENDOMETRIOSIS. IT HAS BEEN INDICATED THAT THE IDENTIFICATION OF EPIGENETIC DIFFERENCES WITHIN THE DNA OR HISTONE PROTEINS MAY CONTRIBUTE TO THE DISCOVERY OF A USEFUL PROGNOSTIC BIOMARKER, WHICH COULD AID IN THE FUTURE EARLIER DETECTION, TIMELY DIAGNOSIS, AND INITIATION OF A NEW APPROACH TO THE TREATMENT OF ENDOMETRIOSIS, AS WELL AS INFORM US ABOUT THE EFFECTIVENESS OF TREATMENT AND THE STAGE OF THE DISEASE. AS THE ETIOLOGY OF ENDOMETRIOSIS IS HIGHLY COMPLEX AND STILL FAR FROM BEING FULLY ELUCIDATED, THE PRESENTED REVIEW FOCUSES ON DIFFERENT APPROACHES TO IDENTIFY THE GENETIC AND EPIGENETIC LINKS OF ENDOMETRIOSIS AND ITS PATHOGENESIS. 2020 16 4310 34 MICRORNAS AND PROGESTERONE RECEPTOR SIGNALING IN ENDOMETRIOSIS PATHOPHYSIOLOGY. ENDOMETRIOSIS IS A SIGNIFICANT DISEASE CHARACTERIZED BY INFERTILITY AND PELVIC PAIN IN WHICH ENDOMETRIAL STROMAL AND GLANDULAR TISSUE GROW IN ECTOPIC LOCATIONS. ALTERED RESPONSIVENESS TO PROGESTERONE IS A CONTRIBUTING FACTOR TO ENDOMETRIOSIS PATHOPHYSIOLOGY, BUT THE PRECISE MECHANISMS ARE POORLY UNDERSTOOD. PROGESTERONE RESISTANCE INFLUENCES BOTH THE EUTOPIC AND ECTOPIC (ENDOMETRIOTIC LESION) ENDOMETRIUM. AN INABILITY OF THE EUTOPIC ENDOMETRIUM TO PROPERLY RESPOND TO PROGESTERONE IS BELIEVED TO CONTRIBUTE TO THE INFERTILITY ASSOCIATED WITH THE DISEASE, WHILE AN ALTERED RESPONSIVENESS OF ENDOMETRIOTIC LESION TISSUE MAY CONTRIBUTE TO THE SURVIVAL OF THE ECTOPIC TISSUE AND ASSOCIATED SYMPTOMS. WOMEN WITH ENDOMETRIOSIS EXPRESS ALTERED LEVELS OF SEVERAL ENDOMETRIAL PROGESTERONE TARGET GENES WHICH MAY BE DUE TO THE ABNORMAL EXPRESSION AND/OR FUNCTION OF PROGESTERONE RECEPTORS AND/OR CHAPERONE PROTEINS, AS WELL AS INFLAMMATION, GENETICS, AND EPIGENETICS. MIRNAS ARE A CLASS OF EPIGENETIC MODULATORS PROPOSED TO PLAY A ROLE IN ENDOMETRIOSIS PATHOPHYSIOLOGY, INCLUDING THE MODULATION OF PROGESTERONE SIGNALING. IN THIS PAPER, WE SUMMARIZE THE ROLE OF PROGESTERONE RECEPTORS AND PROGESTERONE SIGNALING IN ENDOMETRIOSIS PATHOPHYSIOLOGY, REVIEW MIRNAS, WHICH ARE OVER-EXPRESSED IN ENDOMETRIOSIS TISSUES AND FLUIDS, AND FOLLOW THIS WITH A DISCUSSION ON THE POTENTIAL REGULATION OF KEY PROGESTERONE SIGNALING COMPONENTS BY THESE MIRNAS, CONCLUDING WITH SUGGESTIONS FOR FUTURE RESEARCH ENDEAVORS IN THIS AREA. 2022 17 2086 26 EPIGENETIC DYSREGULATION IN ENDOMETRIOSIS: IMPLICATIONS FOR PATHOPHYSIOLOGY AND THERAPEUTICS. ENDOMETRIOSIS IS A PREVALENT GYNECOLOGICAL CONDITION ASSOCIATED WITH PELVIC PAIN AND INFERTILITY. DESPITE MORE THAN A CENTURY OF RESEARCH, THE ETIOLOGY OF ENDOMETRIOSIS STILL ELUDES SCIENTIFIC CONSENSUS. THIS LACK OF CLARITY HAS RESULTED IN SUBOPTIMAL PREVENTION, DIAGNOSIS, AND TREATMENT OPTIONS. EVIDENCE OF GENETIC CONTRIBUTORS TO ENDOMETRIOSIS IS INTERESTING BUT LIMITED; HOWEVER, SIGNIFICANT PROGRESS HAS BEEN MADE IN RECENT YEARS IN IDENTIFYING EPIGENETIC ROLE IN THE PATHOGENESIS OF ENDOMETRIOSIS THROUGH CLINICAL STUDIES, IN VITRO CELL CULTURE EXPERIMENTS, AND IN VIVO ANIMAL MODELS. THE PREDOMINANT FINDINGS INCLUDE ENDOMETRIOSIS-RELATED DIFFERENTIAL EXPRESSION OF DNA METHYLTRANSFERASES AND DEMETHYLASES, HISTONE DEACETYLASES, METHYLTRANSFERASES, AND DEMETHYLASES, AND REGULATORS OF CHROMATIN ARCHITECTURE. THERE IS ALSO AN EMERGING ROLE FOR MIRNAS IN THE CONTROL OF EPIGENETIC REGULATORS IN THE ENDOMETRIUM AND ENDOMETRIOSIS. CHANGES IN THESE EPIGENETIC REGULATORS RESULT IN DIFFERENTIAL CHROMATIN ORGANIZATION AND DNA METHYLATION WITH CONSEQUENCES FOR GENE EXPRESSION INDEPENDENT OF A GENETIC SEQUENCE. EPIGENETICALLY ALTERED EXPRESSION OF GENES RELATED TO STEROID HORMONE PRODUCTION AND SIGNALING, IMMUNE REGULATION, AND ENDOMETRIAL CELL IDENTITY AND FUNCTION HAVE ALL BEEN IDENTIFIED AND APPEAR TO PLAY INTO THE PATHOPHYSIOLOGICAL MECHANISMS OF ENDOMETRIOSIS AS WELL AS RESULTING INFERTILITY. THIS REVIEW SUMMARIZES AND CRITICALLY DISCUSSES EARLY SEMINAL FINDINGS, THE EVER-GROWING RECENT EVIDENCE OF EPIGENETIC CONTRIBUTIONS TO THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS, AND IMPLICATIONS FOR PROPOSED EPIGENETICALLY TARGETED THERAPEUTICS. 2023 18 2275 39 EPIGENETIC REGULATION AND T-CELL RESPONSES IN ENDOMETRIOSIS - SOMETHING OTHER THAN AUTOIMMUNITY. ENDOMETRIOSIS IS DEFINED AS THE PRESENCE OF ENDOMETRIAL-LIKE GLANDS AND STROMA LOCATED OUTSIDE THE UTERINE CAVITY. THIS COMMON, ESTROGEN DEPENDENT, INFLAMMATORY CONDITION AFFECTS UP TO 15% OF REPRODUCTIVE-AGED WOMEN AND IS A WELL-RECOGNIZED CAUSE OF CHRONIC PELVIC PAIN AND INFERTILITY. DESPITE THE STILL UNKNOWN ETIOLOGY OF ENDOMETRIOSIS, MUCH EVIDENCE SUGGESTS THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DISEASE ETIOPATHOGENESIS. THE MAIN RATIONALE IS BASED ON THE FACT THAT HERITABLE PHENOTYPE CHANGES THAT DO NOT INVOLVE ALTERATIONS IN THE DNA SEQUENCE ARE COMMON TRIGGERS FOR HORMONAL, IMMUNOLOGICAL, AND INFLAMMATORY DISORDERS, WHICH PLAY A KEY ROLE IN THE FORMATION OF ENDOMETRIOTIC FOCI. EPIGENETIC MECHANISMS REGULATING T-CELL RESPONSES, INCLUDING DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS, DESERVE ATTENTION BECAUSE TISSUE-RESIDENT T LYMPHOCYTES WORK IN CONCERT WITH ORGAN STRUCTURAL CELLS TO GENERATE APPROPRIATE IMMUNE RESPONSES AND ARE FUNCTIONALLY SHAPED BY ORGAN-SPECIFIC ENVIRONMENTAL CONDITIONS. THUS, A FAILURE TO PRECISELY REGULATE IMMUNE CELL TRANSCRIPTION MAY RESULT IN COMPROMISED IMMUNOLOGICAL INTEGRITY OF THE ORGAN WITH AN INCREASED RISK OF INFLAMMATORY DISORDERS. THE COEXISTENCE OF ENDOMETRIOSIS AND AUTOIMMUNITY IS A WELL-KNOWN OCCURRENCE. RECENT RESEARCH RESULTS INDICATE REGULATORY T-CELL (TREG) ALTERATIONS IN ENDOMETRIOSIS, AND AN INCREASED NUMBER OF HIGHLY ACTIVE TREGS AND MACROPHAGES HAVE BEEN FOUND IN PERITONEAL FLUID FROM WOMEN WITH ENDOMETRIOSIS. ELIMINATION OF THE REGULATORY FUNCTION OF T CELLS AND AN IMBALANCE BETWEEN T HELPER CELLS OF THE TH1 AND TH2 TYPES HAVE BEEN REPORTED IN THE ENDOMETRIA OF WOMEN WITH ENDOMETRIOSIS-ASSOCIATED INFERTILITY. THIS REVIEW AIMS TO PRESENT THE STATE OF THE ART IN RECOGNITION EPIGENETIC REPROGRAMMING OF T CELLS AS THE KEY FACTOR IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS IN THE CONTEXT OF T-CELL-RELATED AUTOIMMUNITY. THE NEW POTENTIAL THERAPEUTIC APPROACHES BASED ON EPIGENETIC MODULATION AND/OR ADOPTIVE TRANSFER OF T CELLS WILL ALSO BE OUTLINED. 2022 19 1892 26 ENDOMETRIOSIS: EPIDEMIOLOGY, CLASSIFICATION, PATHOGENESIS, TREATMENT AND GENETICS (REVIEW OF LITERATURE). ENDOMETRIOSIS IS A "MYSTERIOUS" DISEASE AND ITS EXACT CAUSE HAS NOT YET BEEN ESTABLISHED. AMONG THE ETIOLOGICAL FACTORS, CONGENITAL, ENVIRONMENTAL, EPIGENETIC, AUTOIMMUNE AND ALLERGIC FACTORS ARE LISTED. IT IS BELIEVED THAT THE PRIMARY MECHANISM OF THE FORMATION OF ENDOMETRIOSIS FOCI IS RETROGRADE MENSTRUATION, I.E., THE PASSAGE OF MENSTRUAL BLOOD THROUGH THE FALLOPIAN TUBES INTO THE PERITONEAL CAVITY AND IMPLANTATION OF EXFOLIATED ENDOMETRIAL CELLS. HOWEVER, SINCE THIS MECHANISM IS ALSO OBSERVED IN HEALTHY WOMEN, OTHER FACTORS MUST ALSO BE INVOLVED IN THE FORMATION OF ENDOMETRIOSIS FOCI. ENDOMETRIOSIS IS IN MANY WOMEN THE CAUSE OF INFERTILITY, CHRONIC PAIN AND THE DETERIORATION OF THE QUALITY OF LIFE. IT ALSO REPRESENTS A SIGNIFICANT FINANCIAL BURDEN ON HEALTH SYSTEMS. THE ARTICLE PRESENTS A REVIEW OF THE LITERATURE ON ENDOMETRIOSIS-A DISEASE AFFECTING WOMEN THROUGHOUT THE WORLD. 2021 20 506 37 ASSOCIATION OF ENDOMETRIOSIS WITH CARDIOVASCULAR DISEASE: GENETIC ASPECTS (REVIEW). CARDIOVASCULAR DISEASE (CVD) COMPRISES A BROAD SPECTRUM OF PATHOLOGICAL CONDITIONS THAT AFFECT THE HEART OR BLOOD VESSELS, INCLUDING SEQUELAE THAT ARISE FROM DAMAGED VASCULATURE IN OTHER ORGANS OF THE BODY, SUCH AS THE BRAIN, KIDNEYS OR EYES. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY DISEASE OF THE ARTERIAL INTIMA AND IS THE PRIMARY CAUSE OF CORONARY ARTERY DISEASE, PERIPHERAL VASCULAR DISEASE, HEART ATTACK, STROKE AND RENAL PATHOLOGY. IT REPRESENTS A LEADING CAUSE OF MORTALITY WORLDWIDE AND THE LOSS OF HUMAN PRODUCTIVITY THAT IS MARKED BY AN ALTERED IMMUNE RESPONSE. ENDOMETRIOSIS IS A HERITABLE, HETEROGENEOUS, COMMON GYNECOLOGICAL CONDITION INFLUENCED BY MULTIPLE GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS, AFFECTING UP TO 10% OF THE FEMALE POPULATION OF CHILDBEARING AGE, CAUSING PAIN AND INFERTILITY; IT IS CHARACTERIZED BY THE ECTOPIC GROWTH OF ENDOMETRIAL TISSUE OUTSIDE THE UTERINE CAVITY. OF NOTE, EPIDEMIOLOGICAL DATA OBTAINED THUS FAR HAVE SUGGESTED A LINK BETWEEN ENDOMETRIOSIS AND THE RISK OF DEVELOPING CVD. THE SIMILARITIES OBSERVED IN SPECIFIC MOLECULAR AND CELLULAR PATHWAYS OF ENDOMETRIOSIS AND CVD MAY BE PARTIALLY EXPLAINED BY A SHARED GENETIC BACKGROUND. THE PRESENT REVIEW PRESENTS AND DISCUSSES THE SHARED GENETIC FACTORS WHICH HAVE BEEN REPORTED TO BE ASSOCIATED WITH THE DEVELOPMENT OF BOTH DISORDERS. 2023