Search Results (287)

Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article

Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic ovarian syndrome (PCOS) induced in female rats. PCOS, a complex hormonal disorder, was experimentally induced by administering Letrozole (1 mg/kg) in combination with a high-fat diet for 21 days. The affected rats were then treated with hydro-alcoholic extracts of Fagonia cretica at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg for 20 days. Key biochemical parameters—including serum testosterone, insulin, fasting blood glucose, insulin resistance (HOMA-IR), cholesterol, triglycerides, and lipoprotein levels—were measured. Ultrasound imaging and histopathological analysis of ovarian tissues were also performed. The data were analyzed using computer-based statistical tools, including one-way ANOVA, Cohen’s d effect size, and Tukey’s HSD test, with graphical representations generated using Python 3.10 on the Kaggle platform. Results demonstrated a significant reduction in serum testosterone, insulin, cholesterol, and triglyceride levels (p < 0.05) in treated groups, along with improved ovarian morphology. These findings support the therapeutic potential of Fagonia cretica as a natural treatment for PCOS. Full article

The accumulation of nanoparticles (NPs) in the female body has raised global concerns regarding potential effects on the reproductive system. This study aimed to investigate the toxic effects of nano-titanium dioxide (nano-TiO₂) exposure on the ovaries and the underlying mechanisms. By establishing a nano-TiO₂ accumulation model in mice, our research systematically evaluated the effects of different concentrations of nano-TiO₂ exposure on the development and reproductive endocrine functions of mice. The results showed that nano-TiO₂ exposure significantly reduced the littering rate, sex hormone levels, and ovarian index of mice, and the effects were dose-dependent. Studies on the mechanisms involved revealed that nano-TiO₂ induces an excessive production of reactive oxygen species (ROS), leading to the potential collapse of the mitochondrial membrane and an increase in the apoptosis rate of granulosa cells, thereby triggering oxidative stress and inhibiting the expression of ovarian-specific genes and granulosa-cell function genes. This study reveals the “dual blow” mechanism of nano-TiO₂-mediated ovarian morphology and function through oxidative stress in granulosa cells, namely directly disrupting cellular homeostasis and interfering with the reproductive-related gene network, ultimately leading to decreased ovarian function. This provides experimental evidence for assessing the reproductive risks of nanomaterials in women. Full article

Introduction: Fetal ovarian cysts are known to be a common form of fetal abdominal masses in female fetuses, often resulting from hormonal stimulation in utero. Although many resolve spontaneously without sequelae, others can develop into more complex pathologies, such as intracystic hemorrhage or torsion, which can compromise ovarian integrity and long-term reproductive outcomes. Early detection and appropriate follow-up evaluation are therefore crucial for optimal perinatal management. Materials and Methods: We conducted a retrospective study of 12 cases of fetal ovarian cysts diagnosed by routine prenatal ultrasound examinations over a two-year period at our institution. Inclusion criteria were the presence of a cystic adnexal lesion detected in utero, detailed prenatal ultrasound documentation, and a comprehensive postnatal examination. Sonographic features such as cyst size, internal echogenicity, and signs of vascular compromise were recorded. The mother’s clinical variables, including gestational age at diagnosis and relevant medical conditions, were noted. Postnatal follow-up evaluation consisted of ultrasound examinations and, if indicated, pediatric surgical consultation. Results: Of the 12 cases, 9 were characterized by a simple cystic morphology. All spontaneously regressed postnatally and did not require surgical intervention. Three were defined as complex cysts showing septations or echogenic deposits; one of these cysts required immediate surgical exploration for suspected torsion. No cases with a malignant background were identified. All infants showed a favorable course with normal growth and development until follow-up evaluation. Conclusions: This series emphasizes that most fetal ovarian cysts are benign and often resolve without intervention, highlighting the benefit of systematic prenatal imaging. Nevertheless, complex or large cysts require close prenatal and neonatal monitoring to diagnose complications such as torsion. Full article

Background/Objective: Lifestyle intervention is recommended as first-line treatment for polycystic ovary syndrome (PCOS). This pilot study aimed to determine if a short-term hypocaloric dietary intervention induced changes in the phenotypic presentation of PCOS. Methods: Twenty women with PCOS and overweight/obesity participated in a 3-month hypocaloric dietary intervention with a 6-month follow-up. At pre-intervention, post-intervention, and follow-up, assessments of menstrual cycle status, hyperandrogenism, and polycystic ovarian morphology were performed, and PCOS phenotype status was determined using the following scale of decreasing severity: Phenotype A (ovulatory dysfunction, hyperandrogenism, and polycystic ovaries), Phenotype B (ovulatory dysfunction and hyperandrogenism), Phenotype C (hyperandrogenism and polycystic ovaries), or Phenotype D (ovulatory dysfunction and polycystic ovaries). Results: The participants lost 8 ± 3% of their initial body weight with the intervention (p < 0.001). Eight (40%) participants experienced a favorable shift in PCOS phenotype, while the remaining 12 (60%) participants had an unfavorable shift or no change. Changes in PCOS phenotype were primarily driven by reductions in menstrual cycle length (p = 0.010) and follicle number per ovary (p = 0.017), albeit no baseline clinical variable predicted a favorable-change PCOS presentation. At the 6-month follow-up (N = 12), weight was increased (p < 0.05), and seven participants (58%) had reverted to a more severe phenotype. Conclusions: Weight loss may provide temporary improvement in the phenotypic presentation of PCOS, yet sustained lifestyle change may be required to maintain these benefits. Full article

Objective: Most studies concentrate on comparisons between the cleavage stage and blastocyst stage of embryos during in vitro stimulation treatment. We aimed, in this study, to compare the pregnancy rates of day 4 or day 5 blastocyst transfers, all derived from fresh, antagonist-regulated in vitro fertilization (IVF) cycles, and to evaluate the factors affecting pregnancy success. Methods: This retrospective cohort study evaluated 3681 fresh embryo transfer cycles conducted at a private IVF center between 2019 and 2021. Patients were divided into two groups based on the day of embryo transfer: day 4 (Group 1) and day 5 (Group 2). Subgroup analyses were performed according to age (≤40 vs. >40 years) and the number of oocytes retrieved (≤4 vs. >4). All patients underwent ovarian stimulation with FSH alone or in combination with hMG, and GnRH antagonist protocols were used for pituitary suppression. Final oocyte maturation was triggered with recombinant hCG, and fertilization was achieved via intracytoplasmic sperm injection (ICSI) for all cases. Embryos were cultured in sequential media and assessed daily until transfer on day 4 or day 5, based on embryo morphology and clinic logistics. Results: Pregnancy was more likely among women under 40 than among women over 40. There were a total of 1217 women who underwent day 4 transfer and 2464 women who underwent day 5 transfer. A total of 660 (54.2%) of the women transferred on day 4 developed pregnancy. Among those transferred on day 5, 1610 (65.3%) developed pregnancy. When compared to the 4th day, a single embryo transfer on the 5th day enhances pregnancy success by 1.8 times, while two embryo transfers raise it by 1.6 times. Furthermore, when the number of oocytes is greater than four and the number of embryos transferred is two, the pregnancy success rate is 2.5 times higher when embryo transfer is performed on the fifth day versus the fourth day. Regardless of age, oocyte count, or number of embryos transferred, 5th-day fresh embryo transfers enhanced pregnancy success by 1.9 times compared to 4th-day transfer. Conclusions: Transfers of fresh embryos on day 5 are superior to those on day 4 and should be favored, especially for people over the age of 40, regardless of the number of embryos transferred, even if that individual has fewer than four oocytes. Full article

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen. Full article

Background/Objectives: According to recent reports, the BRAF^V600E mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of this is the appearance of eosinophilic cells (ECs). The aim of the current study was to determine the interobserver reproducibility of ECs and their predictive significance for the detection of the BRAF^V600E mutation in SBTs. Methods: The study was conducted using 63 cases of ovarian SBTs. Three gynecological pathologists, blinded to each tumor’s mutation status, assessed the presence of ECs. Immunohistochemical staining with p16 and Ki-67 was performed to validate ECs. Mutational analysis was carried out using targeted NGS. Results: Genetic analysis revealed 30 BRAF-mutated, 1 NRAS-mutated, and 9 KRAS-mutated SBTs. ECs were identified by the majority of pathologists (two or three) in 78% of the BRAF^V600E-mutated and 11% of the wild-type tumors with other mutations (p < 0.0001). The interobserver reproducibility of the presence of ECs was substantial (κ = 0.66). ECs validated with p16/Ki-67 were identified in 92.6% of the BRAF^V600E-mutated and in 13.8% of the wild-type tumors with other mutations (p < 0.0001). For the ECs identified by the majority of pathologists, the sensitivity and specificity when predicting the BRAF^V600E mutation were 77.8% and 88.9%, respectively. For the ECs validated with p16/Ki-67, the sensitivity and specificity when predicting the BRAF^V600E mutation were 95.3% and 90.5%, respectively. Conclusions: Overall, these results suggest that ECs in SBTs have potential association with the BRAF^V600E mutation. Full article

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H₂S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H₂S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging. Full article

Mesonephric-like adenocarcinoma (MLA) of ovaries is a new and rare neoplastic entity, recently classified by the World Health Organization. Its morphological and immunohistochemical profile is similar to primitive cervical mesonephric adenocarcinoma, but its origin has not been determined yet. Some authors believe that this neoplasm originates from Wolffian remnants in the ovarian hilum, while others suggest an origin from the Mϋllerian epithelium, followed by a mesonephric trans-differentiation. Starting from a recently diagnosed mismatch repair-deficient ovarian MLA, we try to further develop this line of research. A detailed molecular analysis of the studied tumor helps clarify our ideas. In fact, the typical KRAS mutation was not present. We found mutations in numerous other genes, which are rarely described in the literature or are already described in the endometrioid histotype. We reached some interesting conclusions, which, if supported by future studies, will clarify the true nature of these tumors, allowing for better stratification and a better therapeutic framework. Full article

Background/Objectives: This study aims to assess ovarian stromal vascularity using microvascular imaging in reproductive-aged women with polycystic ovarian morphology (PCOM) and to explore its associations with endocrine parameters and polycystic ovary syndrome (PCOS) phenotypes. Methods: We conducted a retrospective, single-center study between January 2021 and November 2023. Women aged 18–49 who met the PCOM criteria (≥20 follicles measuring 2–9 mm or an ovarian volume >10 cm³ in at least one ovary) were included. Pelvic ultrasound with MV-Flow Doppler imaging was used to quantify the stromal vascularity index (VI). On the same day, serum levels of FSH, LH, total and free testosterone, DHEAS, and estradiol were measured. PCOS phenotypes (A, C, D, and non-PCOS) were classified according to the Rotterdam criteria. Statistical analysis involved interobserver agreement using intraclass correlation coefficients (ICCs), correlation analysis for hormonal associations, and group comparisons using ANOVA. Results: A total of 111 women (mean age: 27.4 ± 6.1 years) were evaluated. The mean VI was 43.88 ± 19.84, with good interobserver agreement (ICC = 0.79; 95% CI: 0.65–0.88). VI was highest in Phenotype A (61.36 ± 10.11), followed by Phenotype C (42.57 ± 3.59), Phenotype D (26.47 ± 4.24), and Non-PCOS individuals (9.95 ± 5.44; p < 0.001). VI showed strong positive correlations with total testosterone (r = 0.797) and free testosterone (r = 0.778), and a moderate negative correlation with DHEAS (r = −0.483; p < 0.001). Conclusions: Microvascular imaging is a promising tool for quantifying ovarian stromal vascularity in PCOM. Its strong correlation with androgen levels, especially in hyperandrogenic phenotypes, highlights its potential role in enhancing diagnostic precision and deepening our understanding of PCOS pathophysiology. Full article

Follicular atresia is a natural process of follicular degeneration in mammal ovaries, significantly impacting female reproductive potential. However, the underlying regulatory mechanisms remain underexplored, particularly those involving non-coding RNAs like PIWI-interacting RNAs (piRNAs). In this study, we collected single antral follicles from the ovaries of 180-day-old commercial sows, classified them as healthy (HF) and atretic (AF) based on morphological and biochemical criteria, and sequenced the RNA samples using the Illumina Hiseq 3000 system (San Diego, CA, USA). piRNAs were identified using three algorithms, and the differential expression was compared and validated by qPCR. The target genes of differentially expressed piRNAs were predicted and subjected to functional analysis. A total of 452 piRNAs were identified across all samples, with 103 showing differential expression between HFs and AFs. Among the top 12 piRNAs with the most significant expression differences validated by qPCR, 5 (piR-23, piR-27, piR-64, piR-65, and piR-76) exhibited statistically significant differences. Pathway analysis showed that these piRNAs primarily targeted genes involved in cell apoptosis regulation, inflammation and oxidative stress response, substance transport and signal transduction, and cellular structural integrity maintenance. Our study provides the first comprehensive profile of piRNAs in porcine ovarian follicles during atresia and reveals underlying potential regulatory mechanisms. These findings enhance our understanding of piRNA functions during the early follicular atresia process and offer insights for further functional studies and biomarker development in ovarian pathology. Full article

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

Selective serotonin reuptake inhibitors (SSRIs), like fluoxetine, are increasingly used by women of a reproductive age, raising concerns about their impact on oocyte quality and early embryonic development. This study investigated the effects of chronic fluoxetine exposure on oocyte maturation, ovulation, and embryonic development in a mouse model. Female mice were administered fluoxetine via drinking water, and their reproductive outcomes were compared to those of control mice. Oocyte quantity and quality were assessed following superovulation, including the analysis of spindle morphology, chromatin configuration, and maturation markers. In vitro maturation assays were conducted to evaluate the developmental competence of oocytes exposed to fluoxetine. Finally, the impact of fluoxetine on blastocyst formation, litter size, offspring growth, and ovarian reserve was examined. The results show that fluoxetine treatment reduced the number of ovulated oocytes but did not significantly affect oocyte quality or meiotic spindle formation. Fluoxetine exposure impaired cytoplasmic maturation at the germinal vesicle stage, resulting in a lower proportion of fully mature oocytes and reduced in vitro maturation efficiency. While blastocyst numbers were modestly reduced in fluoxetine-treated mice, litter size and offspring ovarian reserve were unaffected. Unexpectedly, offspring of fluoxetine-treated mothers exhibited increased body weight. These findings suggest that while fluoxetine may impair oocyte developmental competence through disruptions in cytoplasmic maturation, it does not severely compromise overall reproductive outcomes or offspring fertility. Full article