Polycystic Ovary Syndrome Phenotypes Research Articles

PCOS phenotypes and their relationship to aldosterone levels

PCOS phenotypes and their relationship to aldosterone levels

Impact of PCOS phenotypes on quality of life: insights from a serbian pilot study

Impact of PCOS phenotypes on quality of life: insights from a serbian pilot study

MiRNAs specific for PCOS phenotypes

MiRNAs specific for PCOS phenotypes

Polycystic Ovarian Syndrome: Effect of Hormones, Associated Comorbidities and Recent Advances in Therapy

This study addresses the prevalent endocrine disorder, Polycystic Ovarian Syndrome (PCOS), affecting women of reproductive age. The research aims to explore the epidemiology, etiology, genetic factors, transmission patterns, environmental influences, hormonal imbalances, and comorbidities associated with PCOS. The methodology involves a comprehensive review of literature, including studies on PCOS prevalence, diagnostic criteria, phenotype classification, neuroendocrine links, genetic markers, environmental and lifestyle factors, heavy metal exposure, oxidative stress, follicular ER stress, hormonal imbalances, gut hormones, and adipose tissue dysfunction in PCOS. Results point to PCOS having a multigenetic basis, being transmitted across generations, and being influenced by environmental variables. Hormonal imbalances, including androgen excess, insulin resistance, and dysregulation of gonadotropin hormones, are significant in PCOS pathophysiology. The study also discusses the impact of PCOS on infertility, psychological stress, thyroid dysfunction, insulin resistance, dyslipidemia, diabetes,and obesity. The implications of this research highlight the need for a comprehensive strategy to managing PCOS, considering genetic predispositions, environmental exposures, lifestyle modifications, and hormonal imbalances. It also discussed alternative therapies. such as yoga, tai chi, qigong, acupuncture, and Chinese herbal medicine, and discusses the current treatment options for PCOS, including meditative stress reduction, melatonin, and cryptotanshinone.

Phenotypic Characterization of Patients with Polycystic Ovary Syndrome in a Population from the Ecuadorian Andes: A Cross-Sectional Study.

Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in women of reproductive age. Diagnosis is based on the evidence-based international guideline 2018 and the Rotterdam Consensus to classify PCOS phenotypes. This study aims to characterize the biodemographic, clinical, metabolic, and reproductive variables and their relationship with PCOS phenotypes in a population from the Ecuadorian Andes. Methodology: A cross-sectional study was conducted with a non-random consecutive sample of 92 women who attended the outpatient gynecology and endocrinology clinic at the Hospital of the Technical University of Loja (UTPL)-Santa Inés, Loja, Ecuador, between January 2022 and July 2023. Descriptive statistics, mean calculations, standard deviation, parametric and nonparametric tests, odds ratios (OR), confidence intervals (CI), and p-values were employed. Results: The average age was 22 ± 3.4 years, with a predominantly mestizo, urban, single, highly educated, and medium-high socioeconomic level population. It was identified that phenotypes A + B are at a higher risk of developing oligomenorrhea and hypertriglyceridemia compared to phenotypes C + D, with statistically significant differences (p < 0.05). Furthermore, in terms of reproductive variables, phenotypes A + B exhibit a significantly higher frequency of elevated anti-Müllerian hormone (AMH) compared to phenotypes C + D, also with statistical significance (p < 0.05). Conclusions: The classical phenotypes A and B of PCOS are the most common in Ecuadorian Andean women and carry a higher risk of insulin resistance, anovulation, metabolic disorders, and elevated triglyceride levels compared to phenotypes C and D. Ethnic diversity and sociocultural habits influence the prevalence and clinical manifestations of these phenotypes.

Association between serum levels of calcium, magnesium, iron and copper and insulin resistance in women with full blown and not-full blown phenotypes of polycystic ovary syndrome.

The aim of present study was to investigate the association between serum calcium, iron, magnesium, copper levels and insulin resistance in women with full blown phenotype of polycystic ovary syndrome (PCOS) compared to women with not-full blown phenotype. 104 women, aged 18-39, in the first phase of menstrual cycle, diagnosed with PCOS based on the Rotterdam Criteria, were qualified for the study. Patients were divided into two groups: group I contained women with full blown PCOS (phenotype A) and group II contained women with not-full blown PCOS (phenotypes B, C and D). Whole study population was divided on group X containing women with proper insulin sensitivity and group Y containing women with insulin resistance. The study found that women with full blown PCOS had lower level of magnesium compared with not-full blown phenotypes. Also, the level of copper was lower in group with proper insulin sensitivity compared to group with insulin resistance. Serum cooper content showed a negative correlation with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in group with full blown phenotype. Magnesium level showed positive correlation with level of calcium and cooper in group with proper insulin sensitivity. Level of iron content showed a negative correlation with sex hormone binding globulin (SHBG) and HOMA-IR showed a positive correlation with age and body mass index (BMI) in group with insulin resistance. Either level of calcium showed positive correlation with iron and cooper in group with insulin resistance.

Vaginal Microbiota and Proinflammatory Status in Patients with Polycystic Ovary Syndrome: An Exploratory Study.

Background/Purpose: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease most common in patients of childbearing age. This pathology is associated with clinical, metabolic, and reproductive complications. We evaluated the diversity of the vaginal microbiota (VM), the vaginal inflammatory reaction (VIR), the proinflammatory state, and the activation of polymorphonuclear neutrophils (PMN) with the production of neutrophil extracellular traps (NETs). Methods: Thirty-three patients who attended a consultation at the Hospital UTPL-Santa Inés, Loja, Ecuador, from May to August 2023 who were diagnosed with PCOS participated in this study. Blood samples, vaginal discharge, and a survey were obtained. Results: A high number of patients, 23/33 (69.7%), presented altered microbiota in clinical variables associated with PCOS phenotypes A and B, sexual partners (>2), and oligomenorrhoea. A significant statistical association was only observed for sexually transmitted infections at sampling (p = 0.023) and insulin (p = 0.002). All eight cases studied with VIR had PMN/NETotic activity. A high frequency of proinflammatory states was observed in all vaginal microbiota states. Conclusions: These results suggest that the PCOS could trigger a proinflammatory state in the vaginal epithelium independently of the state of the vaginal microbiota. Furthermore, the presence of NETs observed in the cases studied could decrease fertility in these PCOS patients.

Correlation Between Insulin Resistance Indices And Endometrial Thickness To Predict Metabolic Syndrome &amp; Ovulatory Dysfunction In Phenotypes Of Polycystic Ovarian Syndrome In South Indian Population.

Correlation Between Insulin Resistance Indices And Endometrial Thickness To Predict Metabolic Syndrome &amp; Ovulatory Dysfunction In Phenotypes Of Polycystic Ovarian Syndrome In South Indian Population.

Epigenetic/circadian clocks and PCOS.

Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women. It is associated with increased risks of metabolic syndrome, Type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer and non-alcoholic fatty liver disease. Although various susceptibility loci have been identified through genetic studies, they account for ∼10% of PCOS heritability. Therefore, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been described in diseases related to PCOS, such as diabetes, cardiovascular diseases, and obesity. Furthermore, several animal models have illustrated a link between prenatal exposure to androgens or anti-Müllerian hormone and PCOS-like phenotypes in subsequent generations, illustrating an epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMC), adipose tissue, granulosa cells (GC), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls. However, specific hypomethylated or hypermethylated genes have been reported in the different tissues of these women. They are mainly involved in hormonal regulation and inflammatory pathways, as well as lipid and glucose metabolism. Additionally, sleep disorders are present in women with PCOS and disruptions in clock genes' expression patterns have been observed in their PBMC or GCs. While epigenetic changes hold promise as diagnostic biomarkers, the current challenge lies in distinguishing whether these changes are causes or consequences of PCOS. Targeting epigenetic modifications potentially opens avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, data are still lacking in large cohorts of well-characterized PCOS phenotypes. In conclusion, understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS in the future.

Comparing GDF9 in mature follicles and clinical outcomes across different PCOS phenotype

BackgroundPolycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with individualized endocrinology and metabolism. Growth differentiation factor 9 (GDF9) is a candidate as potential biomarker for the assessment of oocyte competence. The effect on oocyte capacity has not been evaluated and analyzed in PCOS phenotypes. ObjectiveWe aimed to screen the expression levels of GDF9 in mature follicles of women with controlled ovarian hyperstimulation (COS) with different PCOS phenotypes. To determine the correlation between the expression level of GDF9 and oocyte development ability. MethodsIn Part 1, we conducted a retrospective study comparing the clinical outcomes and endocrine characteristics of patients with PCOS according to different subgroups (depending on the presence or absence of the main features of polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)) and non-PCOS control group. We stratified PCOS as phenotype A (n = 29), phenotype B (n = 18) and phenotype D (n = 24). In Part 2, the expression of GDF9 in follicular fluid (FF) and cumulus cells (CCs) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. ResultsIn Part 1, the baseline clinical, hormonal, and ultrasonographic characteristics of the study population were matched with the presence or absence of the cardinal features of each PCOS phenotypes showed a clear difference. Phenotypes A and D had statistically significant associations with blastocyst formation and clinical pregnancy compared with phenotypes B (p < 0.001). In Part 2, the levels of GDF9 in FF and CCs for phenotype A and B were significantly were higher than those of phenotype D (P = 0.019, P = 0.0015, respectively). Multivariate logistic regression analysis showed that GDF9 was an important independent predictor of blastocyst formation (P＜0.001). The blastocyst formation rate of phenotype A was higher than that of phenotype B and D (P＜0.001). Combining the results of the two parts, GDF9 appears to play a powerful role in the development of embryos into blastocysts. ConclusionsGDF9 expression varies with different PCOS phenotypes. Phenotype A had higher GDF9 levels and blastocyst formation ability.

AI-algorithm training and validation for identification of endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

BackgroundEndometrial CD138+ plasma cells serve as a diagnostic biomarker for endometrial inflammation, and their elevated occurrence correlates positively with adverse pregnancy outcomes. Infertility-related conditions like polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) are closely associated with systemic and local chronic inflammatory status, wherein endometrial CD138+ plasma cell accumulation could also contribute to endometrial pathology. Current methods for quantifying CD138+ cells typically involve laborious and time-consuming microscopic assessments of only a few random areas from a slide. These methods have limitations in accurately representing the entire slide and are susceptible to significant biases arising from intra- and interobserver variations. Implementing artificial intelligence (AI) for CD138+ cell identification could enhance the accuracy, reproducibility, and reliability of analysis. MethodsHere, an AI algorithm was developed to identify CD138+ plasma cells within endometrial tissue. The AI model comprised two layers of convolutional neural networks (CNNs). CNN1 was trained to segment epithelium and stroma across 28,363 mm2 (2.56 mm2 of epithelium and 24.87 mm2 of stroma), while CNN2 was trained to distinguish stromal cells based on CD138 staining, encompassing 7345 object layers (6942 CD138- cells and 403 CD138+ cells). The training and performance of the AI model were validated by three experienced pathologists. We collected 193 endometrial tissues from healthy controls (n = 73), women with PCOS (n = 91), and RIF patients (n = 29) and compared the CD138+ cell percentages based on cycle phases, ovulation status, and endometrial receptivity utilizing the AI model. ResultsThe AI algorithm consistently and reliably distinguished between CD138- and CD138+ cells, with total error rates of 6.32% and 3.23%, respectively. During the training validation, there was a complete agreement between the decisions made by the pathologists and the AI algorithm, while the performance validation demonstrated excellent accuracy between the AI and human evaluation methods (intraclass correlation; 0.76, 95% confidence intervals; 0.36–0.93, p = 0.002) and a positive correlation (Spearman's rank correlation coefficient: 0.79, p < 0.01). In the AI analysis, the AI model revealed higher CD138+ cell percentages in the proliferative phase (PE) endometrium compared to the secretory phase or anovulatory PCOS endometrium, irrespective of PCOS diagnosis. Interestingly, CD138+ percentages differed according to PCOS phenotype in the PE (p = 0.03). On the other hand, the receptivity status had no impact on the cell percentages in RIF samples. ConclusionOur findings emphasize the potential and accuracy of the AI algorithm in detecting endometrial CD138+ plasma cells, offering distinct advantages over manual inspection, such as rapid analysis of whole slide images, reduction of intra- and interobserver variations, sparing the valuable time of trained specialists, and consistent productivity. This supports the application of AI technology to help clinical decision-making, for example, in understanding endometrial cycle phase-related dynamics, as well as different reproductive disorders.

Effects of the prenatal and postnatal nurturing environment on the phenotype and gut microbiota of mice with polycystic ovary syndrome induced by prenatal androgen exposure: a cross-fostering study.

The gut microbiome is implicated in the pathogenesis of polycystic ovary syndrome (PCOS), and prenatal androgen exposure is involved in the development of PCOS in later life. Our previous study of a mouse model of PCOS induced by prenatal dihydrotestosterone (DHT) exposure showed that the reproductive phenotype of PCOS appears from puberty, followed by the appearance of the metabolic phenotype after young adulthood, while changes in the gut microbiota was already apparent before puberty. To determine whether the prenatal or postnatal nurturing environment primarily contributes to these changes that characterize prenatally androgenized (PNA) offspring, we used a cross-fostering model to evaluate the effects of changes in the postnatal early-life environment of PNA offspring on the development of PCOS-like phenotypes and alterations in the gut microbiota in later life. Female PNA offspring fostered by normal dams (exposed to an abnormal prenatal environment only, fostered PNA) exhibited less marked PCOS-like phenotypes than PNA offspring, especially with respect to the metabolic phenotype. The gut microbiota of the fostered PNA offspring was similar to that of controls before adolescence, but differences between the fostered PNA and control groups became apparent after young adulthood. In conclusion, both prenatal androgen exposure and the postnatal early-life environment created by the DHT injection of mothers contribute to the development of PCOS-like phenotypes and the alterations in the gut microbiota that characterize PNA offspring. Thus, both the pre- and postnatal environments represent targets for the prevention of PCOS and the associated alteration in the gut microbiota in later life.

Ovarian Morphology in Non-Hirsute, Normo-Androgenic, Eumenorrheic Premenopausal Women from a Multi-Ethnic Unselected Siberian Population.

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM). Currently, data on age- and ethnicity-dependent features of PCOM remain insufficient. We aimed to estimate ethnicity- and age-dependent differences in ovarian volume (OV) and follicle number per ovary (FNPO) in a healthy, medically unbiased population of Caucasian and Asian premenopausal women, who participated in the cross-sectional Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384) in 2016-2019. The study population consisted of 408 non-hirsute, normo-androgenic, eumenorrheic premenopausal women aged 18-44 years. All participants underwent a uniform evaluation including a review of their medical history and a physical examination, blood sampling, and pelvic ultrasonography. The statistical analysis included non-parametric tests and the estimation of the upper normal limits (UNLs) by 98th percentiles for OV and FNPO. In the total study population, the upper OV percentiles did not differ by ethnicity or age group. By contrast, the UNL of FNPO was higher in Caucasian women than in Asian women, and women aged <35 years demonstrated a higher UNL of FNPO compared to older women. In summary, these data suggest that the estimation of FNPO, but not OV, should take into account the ethnicity and age of the individual in estimating the presence of PCOM.

PCOS phenotype focus: phenotype D under the magnifying glass.

Polycystic ovary syndrome (PCOS) is defined as the combination of polycystic morphology, hyperandrogenism, and ovulatory disruption; this heterogeneity presents a conundrum for the medical community. The Rotterdam criteria have governed the diagnosis of PCOS, separating the patient cohort into four distinct phenotypes. It has been suggested that the lone normoandrogenic phenotype, so-called phenotype D, should not be classified as a PCOS subtype, with phenotypes A, B, and C displaying a hyperandrogenic biochemical and clinical profile thought to be characteristic of PCOS. To understand how to treat phenotype D patients, this review shines a spotlight on the phenotype, gathering various reports of how phenotype D is differentiated from the other PCOS phenotypes.

Age-related curves of AMH using the Gen II, the picoAMH and the Elecsys assays in women with polycystic ovary syndrome.

Several challenges still exist to adopt the anti-Müllerian hormone (AMH) as a marker of polycystic ovary morphology (PCOM), as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the last years, these studies have mainly been conducted in normo-ovulatory or infertile women. To develop an age-specific percentile distribution of AMH in patients with polycystic ovary syndrome (PCOS) measured by three different assays. Retrospective cross-sectional study. 2,725 women aged 20 to 40 years with PCOS diagnosis were included. Serum AMH measurement by the Gen II (Beckman Coulter), the picoAMH (Ansh Labs), and the Elecsys (Roche) assays. Age-specific centile curves for all the assays and correlations between AMH, clinical, hormonal, and ultrasound characteristics. Age-related nomograms for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of AMH were calculated using the LMS method for all the assays. AMH levels were significantly different between PCOS phenotypes. AMH levels were positive correlated to luteinizing hormone (LH), LH/follicular stimulating hormone (FSH) ratio, testosterone, androstenedione, free androgen index, mean follicular number, and mean ovarian volume. To our knowledge this is the first study reporting age specific percentile nomograms of serum AMH levels measured by the Gen II, the picoAMH and the Elecsys assays in a large population of PCOS women. These findings may help to interpret AMH levels in PCOS patients and facilitate the use of AMH as a diagnostic tool across age ranges.

Experimental animal models for polycystic ovarian syndrome (methods, effects, and implications)

&lt;p class="MDPI17abstract"&gt;Many studies have replicated the clinical and genetic features of polycystic ovarian syndrome (PCOS) using a range of experimental animal models to improve treatment outcomes. This article aims to present an overview of the various experimental animal models that have been used in PCOS research. In this study, we conducted a systematic review of relevant research articles on the induced animal model PCOS. We searched research articles in Indonesian and English published over the last five years through three databases: PubMed, ScienceDirect, Google Scholar. We use established inclusion and exclusion criteria to select suitable articles. Out of 19 research articles included in our systematic review, we found the animal model PCOS based Rotterdam criteria, PCOS-IR model, PCOS-Inflammation model, PCOS-Gut microbiota model and PCOS-syndrome metabolic model. Androgen agents such as testosterone propionate, free testosterone, DHEA, and letrozole, as well as sodium valproate, are effective in the induction of PCOS phenotypes based on the Rotterdam criteria (oligo/amenorrhea, hyperandrogenic, and polycystic ovaries).&lt;/p&gt;

Serum Expression of miR-23a-3p and miR-424-5p Indicate Specific Polycystic Ovary Syndrome Phenotypes: A Pilot Study.

MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of serum miRNAs and polycystic ovary syndrome (PCOS), a common heterogeneous endocrinopathy characterized by hyperandrogenism (HA), oligo- or amenorrhea (OM) and polycystic ovaries. It is not known whether these miRNA profiles also differ between PCOS phenotypes. In this pilot study, we compared serum expression profiles between the four PCOS phenotypes (A-D) and analyzed them both in PCOS (all phenotypes) and in phenotypes with HA by quantitative-real-time PCR (qRT-PCR). The serum expression of miR-23a-3p was upregulated in phenotype B (n = 10) and discriminated it from phenotypes A (n = 11), C (n = 11) and D (n = 11, AUC = 0.837; 95%CI, 0.706-0.968; p = 0.006). The expression of miR-424-5p was downregulated in phenotype C (n = 11) and discriminated it from phenotypes A, B and D (AUC = 0.801; 95%CI, 0.591-1.000; p = 0.007). MiR-93-5p expression was downregulated in women with PCOS (all phenotypes, n = 42) compared to controls (n = 8; p = 0.042). Phenotypes with HA (A, B, C; n = 32) did not show differences in the analyzed expression pattern. Our data provide new insights into phenotype-specific miRNA alterations in the serum of women with PCOS. Understanding the differential hormonal and miRNA profiles across PCOS phenotypes is important to improve the pathophysiological understanding of PCOS heterogeneity.

Letrozole induced a polycystic ovary syndrome model in zebrafish by interfering with the hypothalamic-pituitary-gonadal axis

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women of childbearing age, with an incidence of 5–10%. This study compared the traits of zebrafish with three diagnostic criteria for human PCOS, and the diagnostic criteria for zebrafish PCOS were proposed: decreased fecundity, elevated testosterone (T) or 11-ketotestosterone (11-KT) levels and increased cortical-alveolar oocyte (CO) ratio, enhancing the zebrafish PCOS model's accuracy. According to the mammalian PCOS classification, the type of zebrafsh PCOS is divided into four phenotypes (A, B, C and D), but the four phenotypes of zebrafish PCOS are not fully covered in the existing studies (A and D). In this study, we successfully induced phenotype B zebrafish PCOS model using the aromatase inhibitor, letrozole (LET). That is, wild-type female zebrafish were exposed to 1000 μg/L LET for 30 days. Reproductive tests showed decreased fecundity in female zebrafish exposed to LET (Control: 132.63, 146.00, 173.00; LET: 29.20, 90.00, 82.71). Hormone analysis showed that female zebrafish exposed to LET had significantly lower 17β-estradiol/testosterone (E2/T) ratios, indicating elevated T levels. Meanwhile, levels of 11-KT in the ovaries exposed to LET were significantly up-regulated (Control: 0.0076 pg/μg; LET: 0.0138 pg/μg). Pathological sections of the ovary showed fewer CO in the LET-exposed group (Control: 16.27%; LET: 8.38%). In summary, the zebrafish PCOS model summarized and studied in this study provide a reliable and economical tool for the screening of therapeutic drugs, as well as for the etiology research and treatment strategies of PCOS.

MALAT1 expression in granulosa cells in PCOS patients with different phenotypes

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Role of the mitophagy-apoptosis axis in the pathogenesis of polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its pathogenesis remains largely unknown. This review focuses on how androgen excess influences the molecular basis of energy metabolism, mitochondrial function, and mitophagy in granulosa cells and oocytes, summarizes our current understanding of the pathogenesis of PCOS, and discuss perspectives on future research directions. A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review. Female offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5'-triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS. In conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy-apoptosis axis.