Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome

Endocrine Reviews, Journal Year: 2024, Volume and Issue: 45(4), P. 437 - 459

Published: Jan. 31, 2024

Abstract The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. US Food and Drug Administration has not approved any drug specifically for treating PCOS. As the significance genetics epigenetics rises in development, their pivotal insights have greatly enhanced efficacy success target discovery validation, offering promise guiding advancement PCOS treatments. In this context, we outline genetic epigenetic PCOS, which provide novel into pathogenesis complex disease. We also delve prospective method harnessing strategies to identify potential targets ensure safety. Additionally, shed light on preliminary evidence distinctive associated with gene therapies context

Language: Английский

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The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 21, 2023

Background To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment. Methods Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots used present the results of this meta-analysis. Begg’s and Egger’s tests applied estimate publication bias. Subgroup sensitivity analysis performed check potential sources heterogeneity verify robustness pooled results, respectively. Results A total 14 studies 4182 participants included There was evidence a statistically notable increase clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p 0.05), optimal embryos 1.50, [1.20, 1.88], 0.0004), cumulative 1.73, [1.14, 2.60], 0.009), duration amount required (MD 1.56, [0.47, 2.66], 0.005; SMD 1.51, [0.90, 2.12], < 0.00001), along decrease cycle cancellation 0.78, [0.64, 0.95], 0.02), luteinizing hormone (LH) level on day hCG (SMD -0.81, [-1.10, -0.53], premature LH surge 0.10, [0.07, 0.15], 0.00001) when PPOS used. No bias within revealed. Conclusions Based evidence-based protocol seems improve IVF/ICSI outcomes DOR. More research larger sample sizes rigorous designs are further explore value among diagnosed Systematic review registration www.crd.york.ac.uk , identifier CRD42023430202.

Language: Английский

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Therapeutic Effects and Molecular Mechanism of Chlorogenic Acid on Polycystic Ovarian Syndrome: Role of HIF-1alpha

Nutrients, Journal Year: 2023, Volume and Issue: 15(13), P. 2833 - 2833

Published: June 21, 2023

Chlorogenic acid (CGA) is a powerful antioxidant polyphenol molecule found in many diets and liquid beverages, playing preventive therapeutic role various diseases caused by oxidative stress inflammation. Recent research has that CGA can not only improve clinical symptoms PCOS patients but also follicular development, hormone status, rats, indicating the effect of on PCOS. Notably, our previous series studies demonstrated expression changes regulatory mechanisms HIF-1alpha signaling ovaries. Considering pathway, present article systematically elucidates molecular during treatment CGA, including steroid synthesis, inflammatory response, stress, insulin resistance, order to further understand effects different types provide theoretical basis for promoting CGA-rich beverages simultaneously.

Language: Английский

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A preliminary understanding of the relationship between synthetic phenolic antioxidants and early pregnancy loss: Uncovering the potential molecular mechanisms

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 927, P. 171972 - 171972

Published: March 28, 2024

Language: Английский

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Introduction to Polycystic Ovary Syndrome (PCOS) and Nutritional Challenges

Published: Jan. 1, 2025

Language: Английский

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Fine particulate matter components and reproductive hormones in female adults: A 15-year longitudinal cohort study

International Journal of Hygiene and Environmental Health, Journal Year: 2025, Volume and Issue: 266, P. 114562 - 114562

Published: March 18, 2025

Few cohort studies have evaluated the long-term impacts of ambient fine particulate matter (PM2.5) and its components on reproductive hormone levels in female adults. We conducted a 15-year retrospective study Taiwan between 2003 2017. The two-year average concentrations PM2.5 components, including sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), organic (OM), black carbon (BC), were assessed at each participant's addresses. Linear mixed models used to examine associations with hormones, follicle-stimulating (FSH), luteinizing (LH), testosterone (T), estradiol (E2), prolactin (PRL). Stratified analyses identify vulnerable populations. 17,152 adults included. Each interquartile range (IQR: 3.545 μg/m3) increase was associated 0.585 mIU/mL [95% confidence interval (CI): 0.190-0.980] FSH levels. Among five PM2.5, BC had strongest positive association [each IQR (0.272 0.863 (95% CI: 0.476-1.250) levels], followed by OM, SO42-, NH4+. Similar found for LH, 0.483 0.225-0.742) 0.684 0.431-0.938) LH per BC, respectively. pollutants marginally decreased E2 increased PRL Non-linear FSH, E2, observed. These also positively T among young Post-menopausal women more susceptible chronic components. Our highlighted adverse exposure hormonal homeostasis, revealing biological mechanism air pollution-reproductive health females. Implementing stringent control pollution can benefit adults, even moderately polluted regions.

Language: Английский

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Hormonal and metabolic influences on outcomes in PCOS undergoing assisted reproduction: the role of BMI in fresh embryo transfers

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 28, 2025

This retrospective study aimed to examine the influence of hormonal and metabolic parameters across varying body mass index (BMI) levels on embryo quality pregnancy outcomes in fresh transfer cycles using assisted reproductive technology (ART) patients diagnosed with polycystic ovary syndrome (PCOS). A total 167 women PCOS 266 without (control group) were included. Metabolic was compared between two groups evaluate their relationship outcomes. Subgroup analyses performed assess these effects normal high BMI. In group, such as insulin, blood lipids, luteinizing hormone (LH), anti-Müllerian (AMH) antral follicle counting (AFC) significantly higher than control group. The group also produced more blastocysts a proportion high-quality blastocysts. However, rate clinical rates similar groups, regardless Among high-BMI patients, miscarriage its showed positive correlation BMI, LH, testosterone (TSTO) levels. Hormonal imbalances glucose-lipid metabolism have minimal development patients. factors-particularly BMI-significantly outcomes, elevated BMI androgen increasing risk miscarriage. These findings underscore importance addressing factors management undergoing ART.

Language: Английский

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HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 18, 2023

HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It present in nucleus of eukaryotes and can be actively secreted or passively released by kinds cells. important for maintaining DNA structure binding histones, protecting it from damage. also regulates interaction between histones DNA, affecting packaging, influence gene expression promoting nucleosome sliding. And as DAMP, RAGE TLRs activates NF-κB, which triggers downstream genes like IL-18, IL-1β, TNF-α. known involved numerous physiological pathological processes. Recent studies have demonstrated significance DAMPs female reproductive system. These findings shed light on potential role pathogenesis diseases system possibilities HMGB1-targeted therapies treating them. Such help reduce inflammation metabolic dysfunction alleviate symptoms diseases. Overall, identification key player disease represents significant breakthrough our understanding these conditions presents exciting opportunities development novel therapies.

Language: Английский

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Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 7, 2023

Objective To appraise the current randomized clinical trials (RCTs) for evidence of association growth hormone (GH) with improved outcomes in infertile women diminished ovarian reserve (DOR) undergoing vitro fertilization (IVF). Methods Relevant RCTs published Chinese or English were identified through a comprehensive search nine databases from period database inception to April 20, 2023. We included investigating adjuvant GH during stimulation and reported subsequent outcomes. The group treatment without set up as trial control groups, respectively. quality was measured according Cochrane Collaboration Handbook. Results Of 579 studies initially identified, 10 comprising 852 DOR included. dose individual ranged between 3 5 IU/day. Overall, we judged be at high risk bias blinding domain. Pooled results showed that associated an increased pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) greater number oocytes retrieved (MD 0.91, [0.47, 1.35], 0.0001). Favorable associations also observed when combined therapy improving optimal embryos 1.84, [1.30, 2.59], 0.0005) 0.28, [0.08, 0.48], 0.005) along reducing cycle cancellation 0.46, [0.24, 0.89], 0.02). Moreover, resulted increase 1.33, [1.18, 1.50], 0.00001) embryo implantation 1.56, [1.21, 2.01], 0.0006). In addition, there significant enhancement estradiol levels (SMD 1.18, [0.46, 1.91], 0.001) endometrial thickness 0.75, [0.41, 1.09], on day hCG. With regard total days gonadotrophins used, correlated shorter -0.26, [-0.46, -0.06], 0.01) lower -460.97, [-617.20, -304.73], applied stimulation. Furthermore, conjunction GnRH antagonist protocol more conducive compared agonist ( notable seen IVF than equal 4.5 IU/day hCG 0.05). Conclusion For IVF, protocols better outcomes, dosages gonadotrophin required. well-designed are needed verify our future. Systematic review registration https://www.crd.york.ac.uk PROSPERO (CRD42023421739)

Language: Английский

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Low concentrations of the food contaminant Deoxynivalenol trigger apoptosis and impair GnRH-induced LH secretion in pituitary gonadotrope-like cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

The Fusarium mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. Nearly all individuals are exposed to DON, due it widespread presence in grains and grain-based products. Chronic DON poisoning associated with growth retardation, immunotoxicity as well impaired reproduction fetal development. At molecular level, alters intracellular signaling by activating mitogen-activated protein kinases (MAPKs) that modulate cell growth, differentiation, apoptosis. Of note, these MAPKs also critical mediators gonadotrophin-releasing hormone (GnRH)-induced synthesis secretion follicle-stimulating (FSH) luteinizing (LH) pituitary gonadotrope cells. So far, no research has explored potential endocrine-disrupting effects on gonadotropins production. Herein, we show first evidence affects LH production immortalized gonadotrope-like line LβT2 a concentration-dependent manner. Taken together, our experiments demonstrated low concentrations affect GnRH-induced through mechanism that, at least part, involves apoptosis inhibition phosphorylation ERK-MAPK. Consequently, expression Cga Lhb , two genes for cells mammals. This broadens knowledge toxicity brings new depth neuroendocrine implications reproduction.

Language: Английский

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