When one size does not fit all: Reconsidering PCOS etiology, diagnosis, clinical subgroups, and subgroup-specific treatments

Endocrine and Metabolic Science, Journal Year: 2024, Volume and Issue: 14, P. 100159 - 100159

Published: Jan. 21, 2024

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects large proportion of women. Due to its heterogeneity, the best diagnostic strategy has been matter contention. Since 1990 scientific societies in field human reproduction have tried define pivotal criteria for diagnosis PCOS. The consensus Rotterdam included presence hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology (PCOM), now updated evidence based 2018 2023 International Guideline endorsed by 39 internationally. Within Criteria, at least two out three above-mentioned features are required be present diagnose PCOS, resulting four phenotypes being identified: phenotype A, characterized all features, B, exhibiting hyperandrogenism oligo-anovulation, C, presenting as PCOM finally D oligo-anovulation PCOM, lacking hyperandrogenic component. However, it hypothesis EGOI group C different underlying causality D. Recent studies highlighted strong correlation between insulin resistance role these factors driving alterations, such follicular functional cyst formation. This new understanding PCOS pathogenesis led authors endocrine-metabolic syndromes with metabolic clinical onset. Conversely, absence disturbances suggests origin this condition, point towards novel pathophysiological mechanisms; however, still not fully understood. Further questions raised regarding suitability "phenotypes" described Criteria publication recent GWAS studies, which demonstrated should considered subtypes they reflected genetic picture. Hence, capturing heterogeneity disorder, current may benefit from reassessment evaluation additional parameters endometrial thickness, purpose only improving their accuracy but also assigning an appropriate personalized treatment. In framework, overview aims analyze currently recognized community assess application practice light newly emerging evidence.

Language: Английский

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Effects of Organochlorine Pesticide Residues in Maternal Body on Infants

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 9, 2022

There are many organochlorine pollutants in the environment, which can be directly or indirectly exposed to by mothers, and as estrogen endocrine disruptors cause damage lactation capacity of mammary gland. In addition, because breast milk contains a lot nutrients, it is most important food source for new-born babies. If mothers pesticides (OCPs), lipophilic contaminants accumulate fat passed infant through milk. Therefore, necessary investigate human estimate health risks these breastfed infants. toxic substances mother also fetus placenta, something we need pay attention to. This article introduces several types OCPs, such dichlorodiphenyltrichloroethane (DDT), methoxychlor (MXC), hexachlorocyclohexane (HCH), endosulfan, chlordane, heptachlorand hexachlorobenzene (HCB), mainly expounds their effects on women’s ability health, provides reference maternal health. some measures methods control described here.

Language: Английский

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The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(6), P. 699 - 720

Published: June 23, 2023

Abstract BACKGROUND Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure complications, including hypertensive disorders low birthweight babies. However, the role estrogens in periconceptional period early is still understudied. OBJECTIVE AND RATIONALE This review aims to summarize current evidence on maternal during first trimester pregnancies conceived naturally following ART. Detailed molecular mechanisms related clinical impacts are extensively described. SEARCH METHODS Data for this narrative were independently identified by seven researchers Pubmed Embase databases. The keywords selected: ‘estrogens’ OR ‘estrogen level(s)’ ‘serum estradiol’ ‘estradiol/estrogen concentration’, ‘early pregnancy’ ‘first ‘preconceptional period’ ‘ART’ ‘In Vitro Fertilization (IVF)’ ‘Embryo Transfer’ ‘Frozen Embryo ‘oocyte donation’ ‘egg ‘miscarriage’ ‘pregnancy outcome’ ‘endometrium’. OUTCOMES During (defined here as critical time window starting 1 month before conception), play a crucial endometrial receptivity, through activation paracrine/autocrine signaling. A derailed estrogenic milieu within seems be detrimental both natural ART-conceived pregnancies. Low non-conception cycles On other hand, excessive supraphysiologic concentrations at LH peak correlate lower live birth rates higher complications. In pregnancy, plays massive placentation mainly modulating angiogenic factor expression—and development an immune-tolerant uterine micro-environment remodeling function killer T-helper cells. Lower thought trigger abnormal pregnancies, whereas excess worsen outcomes. WIDER IMPLICATIONS Most available endorses relation between outcomes, further depicting optimal concentration range optimize success. how co-operate factors order maintain fine balance local tolerance towards developing fetus immune responses pathogens remains elusive. Further studies highly warranted, also aiming identify determinants response biomarkers personalized administration regimens

Language: Английский

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Implantation and Decidualization in PCOS: Unraveling the Complexities of Pregnancy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1203 - 1203

Published: Jan. 18, 2024

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, affecting 5–15% globally with large proportion undiagnosed. This review explores the multifaceted nature PCOS and its impact on pregnancy, including challenges fertility due to hormonal imbalances insulin resistance. Despite restoring ovulation pharmacologically, face lower pregnancy rates higher risks implantation failure miscarriage. Our focuses complexities metabolic that impair endometrial receptivity decidualization PCOS. Disrupted estrogen signaling, reduced integrity epithelial tight junctions, resistance window receptivity. Furthermore, progesterone adversely affects decidualization. also examines roles various immune cells inflammatory processes endometrium, contributing condition’s challenges. Lastly, we discuss use rodent models understanding PCOS, particularly those induced by interventions, offering insights into syndrome’s potential treatments. comprehensive underscores need for advanced treatment strategies address complications associated emphasizing intricate interplay hormonal, metabolic, factors.

Language: Английский

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ERβ Regulation of Gonadotropin Responses during Folliculogenesis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10348 - 10348

Published: Sept. 26, 2021

Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of follicles, luteinizing (LH) regulates preovulatory maturation oocytes, ovulation, formation corpus luteum. Cognate receptors FSH LH G-protein coupled that predominantly signal through cAMP-dependent cAMP-independent mechanisms activate protein kinases. Subsequent vital steps in response to gonadotropins mediated activation or inhibition transcription factors required follicular gene expression. Estrogen receptors, classical ligand-activated transcriptional regulators, play crucial roles gonadotropin secretion from hypothalamic–pituitary axis as well function target organs. In this review, we discuss role estrogen receptor β (ERβ) during folliculogenesis. Ovarian follicles Erβ knockout (ErβKO) mutant female mice rats cannot develop beyond antral state, lack oocyte maturation, fail ovulate. Theca cells (TCs) express receptor, whereas granulosa (GCs) both (FSHR) (LHCGR). As oocytes do not somatic a induced maturation. Somatic also high levels receptors; while TCs ERα involved GCs ERβ steroidogenesis primary site ERβ-regulated We observed subset gonadotropin-induced genes GCs, which dependent on ERβ. Thus, plays responses ovary.

Language: Английский

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The estrogen receptor and metabolism

Women s Health, Journal Year: 2024, Volume and Issue: 20

Published: Jan. 1, 2024

Across the globe, metabolic syndrome, hyperuric acid, and their related diseases, such as cardiovascular disease, diabetes, insulin resistance, are increasing in incidence due to imbalances. Due pathogenesis, women more prone these diseases than men. As estrogen levels decrease after menopause, obesity disorders likely occur. Men also affected by acid. To provide ideas for prevention treatment of syndrome hyperuricemia, this article reviews analyzes relationship between receptors, hyperuricemia.

Language: Английский

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Role of ERβ in the ovary and ovary related diseases

Gene, Journal Year: 2024, Volume and Issue: 927, P. 148678 - 148678

Published: June 19, 2024

Language: Английский

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Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 29, 2024

Abstract Background Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, hirsutism. Mutations in the estrogen receptor genes ESR1 ESR2 , involved normal follicular development ovulation, can contribute to PCOS. The present study focuses on investigating potential correlation between single nucleotide polymorphisms (SNPs) incidence this syndrome. Methods For study, SNPs were retrieved from ENSEMBL database analyzed for their effect mutated proteins using different bioinformatics tools SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL HDDOCK. Results All documented deleterious. except rs1583384537, rs1450198518, rs78255744 decreased protein stability. Two variants rs1463893698 rs766843910 gene altered localization i.e. addition nucleus, also found mitochondria extracellular, respectively. rs104893956 rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 rs1384121511 significantly changed secondary structure (2D). that markedly 3D configuration included rs1554259481, rs188957694 rs755667747 rs1463893698, gene. Variants rs1467954450 ( ) rs140630557 ESR2) identified reduce binding tendency ESRα β receptors with estradiol as reflected docking scores -164.97 -173.23, Conclusion Due impact encoded proteins, these might be proposed biomarkers predict likelihood developing PCOS future diagnostic purposes.

Language: Английский

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Short-Chain Chlorinated Paraffins May Induce Ovarian Damage in Mice via AIM2- and NLRP12-PANoptosome

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Humans may intake 0.02 mg/kg/day of short-chain chlorinated paraffins (SCCPs), and no study is available on mammalian ovarian damage caused by low-level SCCPs. In this study, four groups 5-week-old female Institute Cancer Research (ICR) mice were orally administered 0, 0.01, 0.1, 1.0 SCCPs for 21 consecutive days, serum ovaries collected 20 h after the last SCCPs-administration. at ≥0.1 found to reduce follicle counts each stage, induce dose-dependent oxidative stress in mice, lower E2 anti-Müllerian hormone levels. The data indicated that cellular PANoptosis increased all SCCP-treated mice. Furthermore, AIM2- NLRP12-PANoptosome gene protein levels considerably elevated. Female germline stem cells (FGSCs) cortical portion ovary exhibited substantial SCCP groups, additionally, expression FGSC marker genes major proteins was diminished ovaries. Oral administration with resulted Therefore, it suggested oral suppressed function, which be attributed fact induced generation cells.

Language: Английский

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Role of Seed Therapy on Estrous and Non‐Estrous Cycle in Healthy Female Rats

Food Science & Nutrition, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

ABSTRACT Seed cycling therapy (SCT) involves the consumption of specific seeds during follicular and luteal phases menstrual cycle to help balance reproductive hormones. This study aimed investigate effects SCT on healthy female Wistar albino rats prevent hormonal imbalances. For SCT, a seed mixture (SM1) consisting flax, pumpkin, soybeans (estrogenic seeds) was administered at doses 5.4, 4, 8, 12 g per 100 diet non‐estrous phase. Another (SM2) comprising sunflower, sesame, chickpeas (also estrogenic) given 3.12, 8 estrous A total 36 were divided into four groups, each containing nine rats: Basal diet, 1, 2, 3 (SC ). All diets isocaloric iso‐nitrogenous. The results showed that body weight, feed intake, water significantly decreased in SC group ( p < 0.05), with increased nutrient digestibility. tested led significant positive changes levels follicle‐stimulating hormone, luteinizing high‐density lipoproteins (HDL‐c), low‐density (LDL‐c), LDL‐c/HDL‐c ratio, aspartate aminotransferase, alanine aminotransferase across both cycle. There also notable increase estrogen, testosterone, prolactin, insulin 0.05). Ovarian histology normal morphology group, suggesting this dosage most effective. findings indicate further studies are warranted explore genetic mechanisms underlying phytoestrogen action stages.

Language: Английский

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