Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1 DOI Creative Commons
Cai ZhaoWei,

RuoPeng Zhang,

Rongju Liu

и другие.

Journal of Ovarian Research, Год журнала: 2025, Номер 18(1)

Опубликована: Июнь 2, 2025

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease in women of reproductive age. One its core pathologies ovarian granulosa cell (GC) dysfunction, and ferroptosis, as novel death mode dependent on iron ions lipid peroxidation, may be involved the PCOS process, but exact mechanism unknown. Plumbagin (PLB) shows potential treatment due to antioxidant properties. The present study aimed elucidate molecular mechanisms by which PLB ameliorates mitochondrial dysfunction ferroptosis GCs through YTH N6-methyladenosine RNA binding protein 1/L-type amino acid transporter 1 (YTHDF1/SLC7A5) axis. An vitro model was constructed treating KGN cells with dihydrotestosterone (DHT), treatment, YTHDF1 knockdown (si-YTHDF1), SLC7A5 overexpression (pcDNA 3.1-SLC7A5) were intervened respectively. Cell viability measured counting kit-8. Lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) level, ion, peroxidation (LPO) content detected commercial kits. Mitochondrial membrane (MMP) analyzed JC-1 staining combined flow cytometry. Reactive oxygen species (ROS) levels assessed C11-BODIPY probe, oxidative stress indicators including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase kits, Cytochrome C, Ferritin, transcription factor A (TFAM), 4 (GPX4) expression Western blot. Fluorescence situ hybridization, immunoprecipitation, m6A quantitative real-time polymerase chain reaction verified interaction translational regulation SLC7A5. DHT significantly decreased viability, MMP ATP levels, increased LDH ROS, MDA, LPO content, up-regulated C expression, down-regulated TFAM, GPX4 expression. Both reversed above changes, protective effect PLB. co-localized mRNA enhanced translation modification. reduced without affecting weakened knockdown, resulting deterioration function, ferroptosis. DHT-induced inhibiting action regulates Downregulating or enhances GC survival function.

Язык: Английский

Comparative Analysis of Letrozole and Estradiol Valerate PCOS Models: Reproductive and Metabolic Outcomes with and Without High-Fat Diet DOI Creative Commons

Xóchitl Acuña Escalona,

Rocío Ayala,

Karla L. Cortez

и другие.

Biology, Год журнала: 2025, Номер 14(6), С. 592 - 592

Опубликована: Май 23, 2025

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligoanovulation, and polycystic ovarian morphology. Despite its classification as reproductive disorder, PCOS closely associated with metabolic dysregulation, including insulin resistance obesity. An ideal animal model for should replicate both features of the condition. In this study, we compared two widely used postnatal models (letrozole estradiol valerate [EV]) administered alone or combination high-fat diet (HFD), assessing their ability to induce features. Letrozole treatment led significant weight gain increased visceral adiposity, effects that were amplified HFD. Conversely, EV showed tendency toward reduced body mass. While neither significantly altered fasting glucose levels, letrozole combined HFD impaired tolerance, supporting role dysfunction. Hyperandrogenism was more consistently induced EV, aligning clinical phenotypes. Both treatments disrupted estrous cyclicity morphology, though disturbances pronounced model. These findings suggest letrozole, particularly HFD, provides consistent studying facets PCOS.

Язык: Английский

Процитировано

0

Androgens and Hirsutism in a Large Cohort of Portuguese Women DOI Open Access
Joana Pinto, Nicoletta Cera, Claudia Camerino

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(3), С. 673 - 673

Опубликована: Янв. 21, 2025

Background/Objectives: Hirsutism is excessive male-patterned hair in postpubertal women with multifactorial etiology and an indicator of hyperandrogenism associated polycystic ovary syndrome (PCOS). Indeed, it can be caused by the enhanced peripheral conversion androgen precursors to testosterone, as idiopathic hirsutism (IH). Moreover, hirsutism-related hyperandrogenic syndromes like non-classic congenital adrenal hyperplasia (NCAH) (IHA). Methods: In this study, we characterized a large cohort Portuguese referred for estimated prevalence PCOS, NCAH, IHA, IH. The levels androgens gonadotropins body mass index (BMI) were measured compared controls. correlation between each variable was calculated. Results: cohort, found PCOS 56.2%, IH 20.2%, IHA 17.3%, NCAH 6.2%. Subjects only ones showing significant difference BMI controls had lowest sex hormone-binding globulin (SHBG). Those younger more hirsute higher among other androgens. lower luteinizing hormone (LH) LH/follicle-stimulating (FSH) ratios than those PCOS. SHBG free (FAI). IH, particular, adrenal-derived Conclusions: pathogenesis complex, contributions pituitary gland, ovaries, adrenals, adipose tissue, liver have ascertained understand clinical manifestations delineate appropriate treatments. This study sheds new light on fine hormonal regulation these diseases.

Язык: Английский

Процитировано

0

Gut Microbiota Modulation by Inulin Improves Metabolism and Ovarian Function in Polycystic Ovary Syndrome DOI Creative Commons
Lulu Geng, Xin Yang, Jiani Sun

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Abstract The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved gut microbiota, while the underlying mechanism unclear. Here, we investigated role inulin, a microbiota regulator, in alleviation PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism both cohort mice. Consistent cohort, increased abundance microbial co‐abundance group (CAG) 12 mice, including Bifidobacterium species other short‐chain fatty acids (SCFAs)‐producers. We further verified enhancement SCFAs biosynthesis capacity fecal content by inulin. Moreover, decreased lipopolysaccharide‐binding protein (LBP) ameliorated ovarian inflammation whereas intraperitoneal lipopolysaccharide (LPS) administration reversed protective effects Furthermore, transplantation (FMT) from inulin‐treated patients enhanced insulin sensitivity, lipid accumulation thermogenesis, reduced inflammatory response antibiotic‐treated Collectively, these revealed mediates beneficial on dysfunction Therefore, modulating represents promising therapeutic strategy for

Язык: Английский

Процитировано

0

Distribution of polycystic ovary syndrome (PCOS) phenotypes in Iranian women: a cross-sectional study DOI Creative Commons
Asma Kheirollahi,

Hediyeh Hamidi,

Akram Vatannejad

и другие.

BMC Research Notes, Год журнала: 2025, Номер 18(1)

Опубликована: Май 13, 2025

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by diverse clinical and metabolic manifestations. This study aimed to investigate the prevalence of PCOS phenotypes their association with hematological, biochemical, hormonal parameters in PCOS, particular focus on infertile women those recurrent pregnancy loss (RPL). Phenotype A was most prevalent phenotype overall within both RPL subgroups. However, no significant differences or were observed among phenotypes, except for lower RBC hematocrit levels F. demonstrate significantly RBC, hemoglobin,

Язык: Английский

Процитировано

0

Androgen Receptor PROTAC ARV-110 Ameliorates Metabolic Complications in a Mouse Model of Polycystic Ovary Syndrome DOI
Jelina Basnet, Samar Rezq, Alexandra M. Huffman

и другие.

Endocrinology, Год журнала: 2025, Номер 166(7)

Опубликована: Май 19, 2025

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. Hyperandrogenemia (HA) a hallmark of PCOS and positively associated with metabolic complications. Androgens exert their biological actions through androgen receptor (AR), which regulates transcriptional activity. Antiandrogens are not recommended for managing complications due to hepatotoxicity, despite being viable therapy treat HA. We hypothesized that novel AR Proteolysis Targeting Chimera (PROTAC) degrader ARV-110 would downregulate protein levels abolish or mitigate HA-mediated using well-established HA mouse model PCOS. Three-week-old female mice were implanted dihydrotestosterone (DHT) control pellets. Four weeks later, treated low- (ARV-110-L, 1 mg/kg.day) high-dose (ARV-110-H, 10 an additional 8 weeks. dose-dependently reduced white adipose tissue (WAT), kidney, liver, ovary. attenuated DHT-induced increases body weight, fat mass, kidney WAT circulating leptin antimüllerian hormone, altered glucose homeostasis. ARV-110-H increased (UACR, KIM-1, NGAL) liver (ALT, AST, LDH) injury markers caused severe hepatomegaly, while ARV-110-L mostly spared those deleterious effects. Unbiased proteomics analysis revealed treatment severely affected proteome dysregulated multiple signaling canonical pathways, only minimal effects observed treatment. In summary, our findings underscore potential PROTACs as therapeutic approach PCOS, provided dosing carefully optimized avoid adverse

Язык: Английский

Процитировано

0

Assessment of Ovarian Stiffness in Women With Polycystic Ovary Syndrome DOI
Muradiye Yıldırım, Sümeyya Duran Kaymak, Neval Çayönü Kahraman

и другие.

Journal of Ultrasound in Medicine, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Objective To evaluate ovarian stiffness in polycystic ovary syndrome (PCOS) patients with and without metabolic (MetS) using acoustic pulse imaging. Methods This case–control study was conducted a tertiary center PCOS outpatient clinic. A total of 105 participants, 51 (20 MetS 31 non‐MetS) 54 healthy women between the ages 20 35 years, were included study. Laboratory sonographic assessments performed early follicular phase. The shear wave elastography (SWE) technique used to measure tissue transvaginally. Results Age body mass index found be similar control groups. Mean SWE values 13.61 ± 2.2 kPa 8.82 1.62 kPa, groups, respectively; P < 0.001. intraobserver intraclass correlation coefficient value for mean measurement (kPa) 0.811 (good reliability agreement). Using receiver operating curve analysis, an optimized cut‐off point SWE_mean 10.58 determined. Similar subgroups clinical and/or biochemical hyperandrogenism. In MetS, 15.68 1.36 12.28 1.50 respectively ( 0.001). moderate positive waist circumference, triglyceride insulin resistance parameters, weak systolic diastolic blood pressure. Conclusion Ovulatory dysfunction fibroinflammatory environment lead quantitatively measurable changes elasticity. exacerbates these changes. Ovarian elasticity associated laboratory markers.

Язык: Английский

Процитировано

0

Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1 DOI Creative Commons
Cai ZhaoWei,

RuoPeng Zhang,

Rongju Liu

и другие.

Journal of Ovarian Research, Год журнала: 2025, Номер 18(1)

Опубликована: Июнь 2, 2025

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease in women of reproductive age. One its core pathologies ovarian granulosa cell (GC) dysfunction, and ferroptosis, as novel death mode dependent on iron ions lipid peroxidation, may be involved the PCOS process, but exact mechanism unknown. Plumbagin (PLB) shows potential treatment due to antioxidant properties. The present study aimed elucidate molecular mechanisms by which PLB ameliorates mitochondrial dysfunction ferroptosis GCs through YTH N6-methyladenosine RNA binding protein 1/L-type amino acid transporter 1 (YTHDF1/SLC7A5) axis. An vitro model was constructed treating KGN cells with dihydrotestosterone (DHT), treatment, YTHDF1 knockdown (si-YTHDF1), SLC7A5 overexpression (pcDNA 3.1-SLC7A5) were intervened respectively. Cell viability measured counting kit-8. Lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) level, ion, peroxidation (LPO) content detected commercial kits. Mitochondrial membrane (MMP) analyzed JC-1 staining combined flow cytometry. Reactive oxygen species (ROS) levels assessed C11-BODIPY probe, oxidative stress indicators including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase kits, Cytochrome C, Ferritin, transcription factor A (TFAM), 4 (GPX4) expression Western blot. Fluorescence situ hybridization, immunoprecipitation, m6A quantitative real-time polymerase chain reaction verified interaction translational regulation SLC7A5. DHT significantly decreased viability, MMP ATP levels, increased LDH ROS, MDA, LPO content, up-regulated C expression, down-regulated TFAM, GPX4 expression. Both reversed above changes, protective effect PLB. co-localized mRNA enhanced translation modification. reduced without affecting weakened knockdown, resulting deterioration function, ferroptosis. DHT-induced inhibiting action regulates Downregulating or enhances GC survival function.

Язык: Английский

Процитировано

0