Explore the vast range of titles available.

Premature ovarian insufficiency (POI) is the loss of normal ovarian function before the age of 40 years, a condition that affects approximately 1% of women under 40 years old and 0.1% of women under 30 years old. It is biochemically characterized by amenorrhea with hypoestrogenic and hypergonadotropic conditions, in some cases, causing loss of fertility. Heterogeneity of POI is registered by genetic and non-genetic causes, such as autoimmunity, environmental toxins, and chemicals. The identification of possible causative genes and selection of candidate genes for POI confirmation remain to be elucidated in cases of idiopathic POI. This review discusses the current understanding and future prospects of heterogeneous POI. We focus on the genetic basis of POI and the recent studies on non-coding RNA in POI pathogenesis as well as on animal models of POI pathogenesis, which help unravel POI mechanisms and potential targets. Despite the latest discoveries, the crosstalk among gene regulatory networks and the possible therapies targeting the same needs to explore in near future.

Polycystic ovary syndrome (PCOS) is a common disease that has an effect on approximately 10% of women of childbearing age. Although there is evidence regarding the role of lifestyle factors in the development of PCOS, the exact etiology remains unclear. Additionally, metformin is used in the treatment of PCOS but its role remains unclear. We compared the effects of lifestyle modification (LSM) + metformin and metformin alone on PCOS. We performed a systematic review by searching electronic databases for publications until December 2019. The primary endpoints were clinical outcomes, such as menstrual cycles and pregnancy rates, and the secondary endpoints were anthropometric, metabolic, and androgenic parameters. The meta-analysis revealed that there was no significant difference in the improvements in the menstrual cycles between LSM and metformin alone (weighted mean difference [MD] = 1.62) and between LSM + metformin and LSM (MD = 1.20). The pregnancy rates and body mass indices were not significantly different between LSM and metformin alone (MD = 1.44 and −0.11, respectively). LSM reduced insulin resistance (MD = −0.52) and increased serum levels of sex hormone-binding globulins (MD = 8.27) compared with metformin. Therefore, we suggest recommending lifestyle modifications actively to women with PCOS if they do not have indications for metformin.

Background Premature ovarian insufficiency (POI) and natural menopause both involve cessation of ovarian function but occur at different life stages and arise from distinct etiologies. Differentiating between these conditions is essential for appropriate clinical management, particularly in women of reproductive age. Exosomes—extracellular vesicles containing regulatory microRNAs (miRNAs)—offer a promising, non-invasive source of biomarkers for various diseases, including ovarian dysfunction. This study investigated whether urinary exosomal miRNAs can serve as diagnostic markers to distinguish POI from menopause and explore their potential biological relevance. Results We validated POI-associated miRNA expression in urinary exosomes from 11 POI patients and 11 age-matched controls, confirming differential expression of seven candidate miRNAs. We then analyzed urinary exosomal miRNAs from 45 premenopausal and 45 postmenopausal women, which revealed distinct expression patterns: hsa-miR-4516 was consistently elevated in both POI and menopause, whereas hsa-let-7c-5p, hsa-let-7f-5p, and hsa-miR-29a-3p were downregulated in POI but upregulated in menopause. These menopausal expression patterns were mechanistically supported by a 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model, where target proteins of these miRNAs—including STAT3, BCL2, and BCL2L1—were downregulated and p53 was upregulated, consistent with apoptotic pathway activation. To assess diagnostic utility, receiver operating characteristic (ROC) analysis demonstrated strong diagnostic performance, with individual miRNAs yielding AUC values of 0.70 to 0.99 and a combined four-miRNA panel achieving an AUC of 0.99 for distinguishing POI from menopause. Conclusions Urinary exosomal miRNAs demonstrate potential as non-invasive biomarkers for differentiating POI from menopause. Specifically, hsa-let-7c-5p, hsa-let-7f-5p, and hsa-miR-29a-3p may enable clinical distinction between these two conditions, while hsa-miR-4516 may serve as a general indicator of ovarian dysfunction. The combined miRNA panel demonstrated excellent diagnostic performance; however, these findings should be considered hypothesis-generating and require validation in larger, independent cohorts before clinical translation.

Oxidative stress has been proposed as a potential factor associated with the establishment and progression of endometriosis. Although a few studies have shown possible mechanisms which may play roles in development, progression of endometriosis, few are known in regards of initiation of the disease, especially in the relationship with endometrium. The aim of our study was to investigate whether normal endometrium may be changed by Damage-associated molecular patterns (DAMPs), which may contribute developing pathologic endometrium to induce endometriosis. Endometrial tissues were obtained from 10 patients with fibroids undergoing hysterectomy at a university hospital. High mobility group box-1 (HMGB-1), which is a representative DAMP, has been chosen that may induce alteration in endometrium. In preceding immunohistochemistry experiments using paraffin-block sections from endometriosis (N = 33) and control (N = 27) group, retrospectively, HMGB-1 expression was shown in both epithelial and stromal cell. HMGB-1 expression was significantly increased in secretory phase of endometriosis group, comparing to the controls. To examine the alteration of endometrial stromal cell (HESC) by oxidative stress in terms of HMGB-1, cell proliferation and expression of its receptor, TLR4 was measured according to recombinant HMGB-1 use. Cell proliferation was assessed by CCK-8 assay; real-time PCR and western blotting were used to quantify Toll like receptor 4 (TLR4) mRNA and protein expression respectively. A TLR4 antagonist (LPS-RS) and an inhibitor of the NF-κB pathway (TPCA-1, an IKK-2 inhibitor) were used to confirm the relationships between HMGB-1, TLR4, and the NF-κB pathway. Passive release of HMGB-1 was significantly proportional to the increase in cell death (P<0.05). HESCs showed significant proliferation following treatment with rHMGB-1 (P<0.05), and increased TLR4 expression was observed following rHMGB-1 treatment (P<0.05) in a concentration-dependent manner. Treatment with a TLR4 antagonist and an NF-κB inhibitor resulted in suppression of rHMGB-1-induced HESC proliferation (P<0.05). Levels of IL-6 were significantly decreased following treatment with an NF-κB inhibitor (P<0.05). Our results support the development of altered, pathological endometrium resulted from oxidative stress in normal endometrium. These findings may provide important insights into the changes in endometrium linking the development and progression of endometriosis.

Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux.

Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea that lasts for a minimum of four months in women < 40 years old and is typically characterized by reduced estrogen levels and elevated serum concentrations of follicle-stimulating hormone. We collected urine samples from two participant cohorts from Gil Hospital of Gachon University (Incheon, Korea): a sequencing cohort of 19 participants (seven patients with POI (POI patients without Turner syndrome), seven patients with Turner syndrome (POI patients with Turner syndrome), and five control individuals (age-matched controls with confirmed ovarian sufficiency)) and a validation cohort of 46 participants (15 patients with POI, 11 patients with Turner syndrome, and 20 control individuals). Among differentially expressed miRNAs, hsa-miR-4516 was significantly upregulated in patients with POI in both cohorts, independent of the presence of Turner syndrome. Moreover, the upregulation of miR-4516 was confirmed in the ovary—but not in the uterus—of a cyclophosphamide and busulfan-induced POI mouse model. This was accompanied by a decrease in STAT3 protein level, a predicted target of miR-4516, via miRTarBase2020. Our study provides compelling evidence that miR-4516 is highly expressed in patients with POI and POI mouse models, suggesting that miR-4516 is a diagnostic marker of POI.

This study aimed to investigate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome along with its associated risk factors in Korean postmenopausal women. This study was performed using data from the KNHANES 2008-2010 study and included 4,364 postmenopausal Korean women. Clinical and other objective characteristics, seasonality, and presence of metabolic syndrome with its five components were evaluated and correlated with the serum levels of 25(OH)D. Although no statistically significant associations were observed between the levels of serum 25(OH)D and the prevalence of metabolic syndrome, the adjusted OR for elevated blood pressure, elevated triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C) showed tendency to decrease sequentially as tertiles of serum 25(OH)D levels increased (p for trends  = 0.066, 0.043, and 0.010, respectively). Women in the highest tertile of serum 25(OH)D showed a significant decrease in the prevalence of elevated blood pressure, elevated TGs, and reduced HDL-C as compared with those in the lowest tertile of serum 25(OH)D (p = 0.020, 0.014, and 0.002, respectively). Based on these results, we consider that adequate serum levels of 25(OH)D in Korean postmenopausal women may not entirely indicate a lower risk of developing metabolic syndrome. However, adequate serum levels of 25(OH)D are significantly associated with a decrease in elevated blood pressure, elevated TGs, and reduced HDL-C levels in postmenopausal women.

Background: Although many menopausal Asian women use herbal remedies for joint pain, there are no studies evaluating the efficacy of Korean red ginseng on osteoarthritis symptoms in postmenopausal women. The purpose of this study is to analyze antioxidant enzyme activity, oxidative stress markers, and pain scores before and after red ginseng consumption, to assess its effect in postmenopausal women. Methods. This prospective, double-blind, randomized controlled trial enrolled 52 postmenopausal women who presented with hand edema and/or pain and were diagnosed as degenerative arthritis of the hand. Patients were randomly assigned to the red ginseng (RG) group (supplemented with 3 g/d of RG for 12 weeks) or the placebo group. Changes in pain and Disability of the Arm, Shoulder, and Hand (DASH) scores, antioxidant enzyme, oxidative stress markers, serum estradiol levels, and endometrial thickness were analyzed. Results. The pain score and DASH score were significantly improved in the RG group (both p < 0.05). The improvement of pain score at rest, during work or sport, and DASH score was significant compared to that of the placebo group. The superoxide dismutase level increased ( p < 0.05) and the malondialdehyde level decreased ( p < 0.05) significantly in the RG group, while none of the antioxidative factors showed a significant change in the placebo group. Serum estradiol levels and endometrial thickness were not affected by RG supplementation. Conclusion. RG may be an effective dietary supplement for postmenopausal women with degenerative osteoarthritis of the hand. It may relieve pain and improve antioxidative activity without the risk of endometrial thickening.

As women go through menopause, serum estrogen decreases and ferritin increases. Decreased serum estrogen is well known to cause detrimental effects on bone health; however, data on the associations of serum ferritin with BMD before and after menopause are still lacking. Therefore, this study aimed to investigate the association between serum ferritin levels and BMD in premenopausal and postmenopausal Korean women. This study was performed using data from the 2008-2010 Korean National Health and Nutrition Examination Survey, including 7300 women (4229 premenopausal and 3071 postmenopausal). BMD was measured using dual X-ray absorptiometry at the femur and the lumbar spine, and serum ferritin levels were measured by chemiluminescent immunoassay. Median serum ferritin levels in postmenopausal women were higher than those in premenopausal women despite the same age ranges. Serum ferritin levels were only significantly correlated with BMD on the lumbar spine (β = -0.189, p-value = 0.005) in premenopausal women after adjusting confounding factors. Additionally, BMD on the lumbar spine had tended to decrease as serum ferritin quartiles increase (P for trend = 0.035) in premenopausal women after adjusting confounding factors. On the other hand, there were no significant associations between serum ferritin levels and BMD on the total femur and, femur neck in premenopausal women, and BMD on the total femur, femur neck, and lumbar spine in postmenopausal women. Increased serum ferritin levels were significantly associated with BMD in premenopausal women, particularly on the lumbar spine, but not in postmenopausal women.

[This corrects the article DOI: 10.1371/journal.pone.0148165.].