Ovarian Disease Research Articles

Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa-Ephb2 Pair.

Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant-derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder-free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo-time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A-Eph receptor B2 ligand-receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant-derived compounds.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Melatonin protects against particulate matter-induced ovarian dysfunction by activating the Nrf2 signaling pathway to alleviate ferroptosis

Accumulating evidence suggests that exposure to ambient airborne PM2.5 increases the risk of primary ovarian insufficiency (POI). However, whether ferroptosis, a newly discovered type of cell death involved in PM2.5-induced lung injury and fibrosis, is involved in PM2.5-induced POI has not been determined. This study aimed to verify the involvement of PM2.5-induced ferroptosis in ovarian dysfunction and further demonstrate that melatonin inhibits ferroptosis by activating the Nrf2 signaling pathway to ameliorate POI in vivo and in vitro. In our study, PM2.5 promoted iron accumulation and induced lipid peroxidation, thus contributing to ferroptosis in KGN cells and ovaries. However, these effects were eliminated and enhanced in Nrf2-overexpressing and Nrf2-knockdown cells, respectively. In addition, melatonin and ferrostatin-1 (Fer-1) inhibited ferroptosis by activating the NRF2 signaling pathway, as evidenced by the silencing of Nrf2 in vivo and in vitro. Mechanistically, Nrf2-knockout mice were more susceptible to ferroptosis and PM2.5-induced POI than control mice. Moreover, melatonin suppressed changes in morphological and biochemical indicators related to ferroptosis, such as MDA and GSH depletion and GPX4 and XCT downregulation, by enhancing Nrf2 signaling. Here, we first reported that PM2.5 triggered ferroptosis by increasing ROS levels, lipid peroxidation and glutathione depletion. Notably, melatonin significantly decreased ferroptosis levels and improved ovarian function by activating the NRF2 signaling pathway in vivo and in vitro.

Exosome's role in ovarian disease pathogenesis and therapy; focus on ovarian cancer and failure

Exosome's role in ovarian disease pathogenesis and therapy; focus on ovarian cancer and failure

The mitochondrial DNA copy number and ovary-related reproductive disorders: A bidirectional two-sample Mendelian randomization study.

In the present study, a bidirectional two-sample Mendelian randomization approach was utilized to explore potential causal relationships between mitochondrial DNA copy number (mtDNA-CN) and ovary-related reproductive disorders (ORRDs), including ovarian dysfunction, ovarian cyst, polycystic ovary syndrome (PCOS), premature ovarian failure (POF) and ovarian endometriosis. Genetic associations with mtDNA-CN were obtained from three genome-wide association study (GWAS) summary statistics from the UK Biobank, and ORRD data were investigated using summary statistics from the FinnGen cohort. Single nucleotide polymorphisms (SNPs) correlated with mtDNA-CN were selected as genetic instrumental variables (IVs) to estimate the causal effect of mtDNA-CN on ORRDs using the inverse-variance weighted (IVW) method with heterogeneity and pleiotropy analysis, and we repeated this in the opposite direction using instruments for ORRDs. We found that the genetically predicted mtDNA was indicative of increased levels of PCOS (OR = 1.16; P < 0.001) and ovarian endometriosis (OR = 1.25; P = 0.007) in the IVW analysis and was not associated with the risk of other ORRDs. In the reverse direction, genetically predicted ORRDs were not associated with mtDNA-CN levels in the IVW analysis. Sensitivity and replication analyses showed the results to be stable. We found that mtDNA-CN may increase the risk of PCOS and ovarian endometriosis. This may have implications for mtDNA-CN as a biomarker for these conditions in clinical practice.

Thyroid Disorders in Patients with Polycystic Ovarian Syndrome in a Tertiary Care Center: An Observational study

Introduction: Polycystic ovarian syndrome is the most common endocrine and metabolic disorder in women of childbearing age, affecting 3–15% of women worldwide, leading to reproductive, metabolic, and psychological issues. Patients with polycystic ovarian syndrome require rigorous thyroid function detection, monitoring, and correction over time. In this study, we aimed to evaluate the clinical presentations and thyroid dysfunction in patients with polycystic ovarian syndrome.Methods: An observational study was done in patients with polycystic ovarian disease presenting to a tertiary care centre over six months, from December 2023 to May 2024 Total population sampling was done. All the women during the study period diagnosed with polycystic ovarian disease based on Rotterdam criteria were included in the study after getting ethical approval from the institutional review board. (Reference number: 20102023/03).Results: The mean age of women in the study was 24.74±5.01 years. A total of 28 (31.46%) patients of polycystic ovarian disease had hyperthyriodism, hypothyroidism was found in 13 (14.60%) and subclinical hypothyroidism was found in 6 (6.74%) patients. All the women had menstrual irregularities. Regarding androgenic characteristics, 53 (59.55%) of patients presented with hirsutism, 43 (48.51%) presented with acne, 13 (14.61%) women had alopecia, and 4 (4.49%) women had acanthosis.Conclusions: Hyperthyroidism, hypothyroidism and subclinical hypothyroidism were prevalent in polycystic ovarian disease patients, emphasizing the need for thorough thyroid evaluation in polycystic ovarian disease patients due to its impact on metabolic and reproductive health. High rates of menstrual irregularities, androgenic symptoms like hirsutism and acne, and fertility challenges were also prevalent, aligning with findings from similar studies.

A ketogenic diet alleviates the apoptosis of granulosa cells by inhibiting the activation of cGAS-STING signaling pathway in PCOS mice

BackgroundPolycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The ketogenic diet (KD), a diet high in fat and low in carbohydrates, has been applied clinically for the treatment of obese women with PCOS. We have previously demonstrated that KD improved the reproductive phenotype in an androgen-induced PCOS mouse model, yet the underlying molecular mechanisms remain largely unclear. The aim of the present study was to investigate the effect of KD on the reproductive phenotype of a letrozole-induced PCOS mouse model.MethodsFemale C57BL/6N mice were divided into three groups, designated control, letrozole, and letrozole + KD groups. Mice of control and letrozole groups were fed the control diet, whereas letrozole + KD mice were fed a KD with 89.9% (kcal) fat for 3 weeks after the PCOS mouse model was generated. β-hydroxybutyrate (BHB), the most abundant ketone body in the body, was used to treat KGN cells with testosterone (T) to simulate the KD effect on PCOS mouse ovaries in vitro.ResultsOur data showed that KD treatment significantly increased blood ketone levels and reduced body weight. Ovarian functions were improved in some letrozole + KD mice. Results from in vitro experiments indicated mitochondrial damage owing to high T levels, which resulted in the leakage of cytochrome C and mitochondrial DNA into the cytosol and thus induced the activation of the intracellular caspase cascade and the cGAS-STING-NF-κB pathway, leading to granulosa cell inflammation and apoptosis. BHB exhibited certain protective effects on mitochondria of T-treated KGN cells via inhibiting the cGAS-STING pathway. Moreover, the cGAS-STING pathway was activated in ovaries of letrozole mice and was down-regulated in letrozole + KD mice.ConclusionThese findings, for the first time, revealed that hyperandrogenism induced ovarian dysfunction possibly through activation of the cGAS-STING pathway, which could be partially inhibited by ketone bodies produced from KD administration.

SnRNA-seq of human ovaries reveals heat shock proteins are associated with obesity related cancer risk

BackgroundObesity significantly impacts female reproductive health and increases the risk of gynecological tumors. However, the specific transcriptional changes that occur in the ovarian microenvironment during obesity-induced stress and the relationship between obesity and ovarian cancer remain unclear.MethodsOur study investigated the single-cell landscape of the ovarian cortex in individuals with varying BMI levels by snRNA-seq, revealing weight-stage related cellular composition deviations and expression profile irregularities. Results: Using single-cell high-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA), we identified distinct obesity-related gene modules within various subpopulations of stroma cells and blood vascular endothelial cells. Notably, we observed a negative correlation between BMI and heat shock protein (HSP) family genes. Specifically, we found that HSPD1 might function as a potential regulator of ovarian carcinogenesis and progression under conditions of obesity, as supported by our co-analysis with data from three bulk RNA-seq ovarian cancer databases. Our findings suggested that lower expression of HSPD1 indicated a poorer prognosis for ovarian cancer.ConclusionsOur study identified a cluster of genes in ovarian cells that are suppressed by obesity, including those belonging to HSP family genes. These findings provide valuable insights for investigating the link between obesity and ovarian diseases.

Evaluation of salivary total antioxidant capacity and malondialdehyde in pre-menopausal and post-menopausal women

Menopause is a natural and expected stage of development that occurs in the life of a woman and is characterized by the permanent end of menstruation. Ovarian dysfunction is a result of permanent alterations to the ovaries’ reproductive and hormonal activities. The reproductive system of a woman is not the only thing that is impacted by fluctuations in hormone levels. Hormones have powerful influence on the development of the skeleton and the mouth cavity, as well as on the integrity of these structures. The oral cavity is significantly affected by them. Different stages of a woman’s life, such as puberty, menstruation, pregnancy, and menopause, each have their own unique impact on the oral health. Oxidative stress is a condition that occurs when there is an imbalance between oxidants and antioxidants, with the former making it possible for living cells to sustain damage. Lipid peroxidation and the subsequent breakdown products, such as malondialdehyde (MDA), are formed, and these compounds can be observed in biological fluids. Total antioxidant capacity is a term that is frequently used to refer to the antioxidant activity of the “nonspecific” antioxidant pool.The objective: to assess of salivary total antioxidant capacity, salivary malondialdehyde, salivary pH in pre-menopausal and post-menopausal women and correlation between pH and salivary biomarkers. Materials and methods. A case-control study was conducted in 80 healthy women. The study included 80 females between the ages of 40 and 55 years; specifically, 40 persons were premenopausal and 40 women were postmenopausal.In the saliva of the patients, the total antioxidant capacity (TAC) and MDA level were determined using the immunoassay method, and the pH level was also studied. Data description, analysis and presentation were performed using Statistical Package for social Science (SPSS version 22, Chicago, Illinois, USA). Results. The findings indicated that the pH value in the post-menopausal group was significantly higher than that of the pre-menopausal group. In comparison to the post-menopausal group, the pre-menopausal group exhibited a significantly higher level of TAC. While MDA level was significantly greater in the post-menopausal group than in the pre-menopausal group. A significant correlation of salivary pH with biomarkers of TAC and MDA of saliva was found, but there was no significant correlation between MDA and TAC in premenopausal women. On the other hand, there is a non-significant negative correlation between salivary TAC and pH level, as well as an insignificant correlation of MDA with pH and salivary TAC in postmenopausal patients. Conclusions. There are differences in salivary total antioxidant capacity and malondialdehyde level between pre-menopausal and post-menopausal women.

Morphological and Redox/Glycative Alterations in the PCOS Oviducts: Modulating Effects of Carnitines in PCOS Mice

Polycystic ovarian syndrome (PCOS) is a heterogeneous condition characterized by hyperandrogenism (HA), polycystic ovaries, and dysfunctional ovulation, and it is associated with metabolic problems such as insulin resistance (IR) and obesity. After having investigated the morphological and antioxidant/antiglycative alterations on mouse ovaries and uteri, we here focus on PCOS oviducts, a tract of the reproductive system essential for the nourishment and transport of gametes and embryos. The modulating effects of L-carnitine (LC) and acetyl-L-carnitine (ALC) were also assessed. CD1 mice were administered or not with dehydroepiandrosterone (DHEA, 6 mg/100 g body weight) for 20 days, alone or with 0.40 mg of L-carnitine (LC) and 0.20 mg of acetyl-L-carnitine (ALC). Oviducts were then subjected to histology and immunohistochemistry to evaluate their morphology and collagen deposition, and steroidogenesis. Oxidative, mitochondrial, and methylglyoxal (MG)-dependent damage was also investigated. Transmission electron microscopy was used to detect ultrastructural alterations. The PCOS oviducts were affected by hyperfibrosis, hyperplasia, hypertrophy, and altered steroidogenesis, with oxidative alterations associated with MethylGlyoxal-Advanced Glycation End product (MG-AGE) accumulation. A reduced ciliary coverage and numerous dilated intercellular spaces were found in the epithelium. LC-ALC administration mitigated PCOS oviductal alterations. These results provide evidence for the detrimental action of oxidative and glycative stress in PCOS oviducts, confirming a protective role of carnitines on the PCOS phenotype.

Study to Evaluate the Effectiveness of Structured Teaching Programme in Knowledge Regarding Polycystic Ovarian Syndrome (PCOS) among 1st Year B.Sc. Nursing Student of Smt. Nagarathnamma College of Nursing

Background of Study: Polycystic Ovarian Syndrome or disease (PCOS/PCOD), originally described in 1935 by Stein and Leventhal, is a complex, heterogeneous disorder of uncertain etiology, with a large degree can be classified as a genetic disease. It is thought to be the most frequent endocrine problem of women in reproductive age. In India nearly 40% of the women are affected by polycystic ovarian syndrome or disease (PCOD). But among then only 60% come to hospital for treatment, when they recognize that they have got infertility. Method: Evaluative approach is adopted to study as its aim is to test hypothesis that establishes relationship between polycystic ovarian syndrome (PCOS) and reduction in conditions. Pilot study was conducted with six samples in selected college to refine methodology and to find feasibility of study. Result: There was significant improvement in the knowledge of students following the administration of structured teaching program on Polycystic Ovarian Syndrome. Conclusion: The present study attempted to assess knowledge regarding polycystic ovarian syndrome. The study findings showed that the post test score was higher than the pre-test score and was concluded that structure teaching program on polycystic ovarian syndrome was effective.

Menstrual challenges in puberty: Investigating menorrhagia in adolescent girls

Menorrhagia, defined as excessive or prolonged menstrual bleeding, poses a significant challenge during this developmental stage, potentially impacting the health and well-being of adolescent girls. Despite its prevalence, comprehensive studies on menorrhagia in this specific demographic are scarce. This study aims to address this gap by investigating the underlying causes and treatment outcomes of puberty menorrhagia.A six-month observational study involving 50 adolescent girls presenting with menorrhagia was conducted at the Department of Obstetrics and Gynecology in a tertiary care center. The study utilized consecutive enumerative sampling and included a thorough investigation of participants, collecting data on demographic profiles, symptom severity, anemia levels, diagnoses, therapy requirements, and responses to conservative management. Baseline investigations encompassed a range of tests, including pregnancy exclusion, complete blood count, coagulation profile, and hormonal assays.The study cohort of 50 participants revealed varying characteristics: 24% were under 14 years, 34% were between 14-16 years, and 42% were aged 17-19 years. BMI distribution showed 14% below 18.5, 76% between 18.5 and 25, and 10% exceeding 25. Symptom duration included 20% reporting less than 6 months, 34% between 6-12 months, and 46% over 12 months. Etiology analysis indicated 60% with ovulatory dysfunction. Hemoglobin level analysis illustrated the prevalence and severity of anemia. Diverse treatments, including hormonal and non-hormonal interventions, were administered.This study provides insights into the causes of puberty menorrhagia, emphasizing the need for a holistic treatment. Future research should delve deeper into identified associations and clinical variants to enhance our understanding and guide effective interventions. Management should be directed to the cause.

Cutting-Edge Deep Learning Strategies for Precise Ovarian Disease Detection: A Comprehensive Review

Accurate and timely diagnosis of ovary-related diseases is of paramount importance in the realm of medical imaging. Utilizing deep learning technology has emerged as a viable method to improve the precision and effectiveness of medical image segmentation, which directly impacts the detection of ovarian diseases. Ovarian disease detection through medical image segmentation is critical for early diagnosis and effective treatment. This study evaluates cutting-edge deep learning strategies using the MMOTU ovarian tumour ultrasound dataset, which includes OTU 2D and OTU CEUS subsets. We implemented various models, including U-Net, its variants with ResNet and DenseNet backbones, CR-Unet, and Ocys-Net, along with ensemble learning and transfer learning techniques. Results show that while the baseline U-Net is effective, advanced models, particularly CR-Unet and DenseNet, significantly improve segmentation accuracy. The best performance was achieved using an ensemble model and a fine-tuned pre-trained network, highlighting the potential of these approaches in enhancing the precision and reliability of ovarian disease detection.

Cumulus cell DNA damage linked to fertilization success in females with an ovulatory dysfunction phenotype.

Intracytoplasmic sperm injection (ICSI) is a widely used technique in fertility centers. ICSI success depends on both nuclear and cytoplasmic oocyte maturation. Cumulus cells, which surround the oocytes, play a pivotal role in oocyte competence. However, the significance of DNA damage in cumulus cells as a marker of fertilization success remains largely unexplored. This study aims to investigate the relationship between DNA damage in cumulus cells of females undergoing ICSI, and oocyte competence, with a focus on in vitro fertilization (IVF) outcomes. We employed the alkaline comet assay to assess DNA damage levels (%TDNA) in cumulus cells and whole blood from 22 potentially fertile females and 35 infertile females, including 20 with an ovulatory disfunction phenotype. Our results revealed significant differences between the levels of %TDNA in cumulus cells and blood. Females with an ovulatory dysfunction phenotype exhibited higher levels of %TDNA in cumulus cells compared to potentially fertile females. Additionally, within the group of females with ovulatory dysfunction, a significant correlation was observed between %TDNA levels and the number of oocytes with two pronuclei. Our findings suggest that blood does not accurately reflect DNA damage in cumulus cells, which was correlated with the fertilization success in females with ovulatory dysfunction. High levels of %TDNA in cumulus cells were associated with a higher likelihood of successful fertilization. Moreover, our results imply that low levels of %TDNA may be linked to oocytes that fail to complete maturation and, consequently, do not fertilize (oocytes with zero pronuclei). Further research with larger cohorts is necessary to validate these findings and to explore potential applications in female fertility. However, our study provides evidence that DNA damage in cumulus cells may serve as a valuable biomarker for predicting fertilization success and oocyte competence.

MTOR inhibitors potentially preserve fertility in female patients with haematopoietic malignancies: a narrative review.

Haematologic malignancies are considered among the more common adolescent and young adult (AYA) cancers. Many female AYA patients with haematopoietic malignancies face impaired fertility. Haematologic malignancies patients tend to be treated with more aggressive systemic chemotherapy than that of solid tumours. In adult women, treatment-related contraception causes age-related fertility loss. Graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation is associated with decreased fertility. Ovarian cryopreservation is often indicated for haematopoietic malignancies; however, follicle loss associated with ovarian cryopreservation and ovarian minimal residual disease, which result in the withdrawal of the transplantation, are important issues. These problems may not be fully addressed by conventional methods of fertility preservation, such as oocyte, embryo, and ovarian cryopreservation, leaving room for research into new treatment approaches, such as fertility preservation drugs. In recent years, preclinical studies have shown that mTOR inhibitors may preserve chemotherapy-induced follicular loss, may have follicle-preserving effects on follicle loss associated with cryopreservation and transplantation of ovarian tissue, may have fertility-preserving effects on aging-related infertility. Clinical studies have shown that mTOR inhibitors may have the potential for indirect fertility preservation by controlling GVHD, have a limited anti-tumor effect against haematopoietic malignancies. The purpose of this article is to outline the various issues faced by female survivors of haematopoietic malignancies and discuss the potential of mTOR inhibitors as a safe treatment option. Based on current research, mTOR inhibitors seem promising and innovative fertility preservation agents regarding preclinical conditions, and further study, including clinical trials, should be expected.

Apigenin Improves Ovarian Dysfunction Induced by 4-Vinylcyclohexene Diepoxide via the AKT/FOXO3a Pathway.

Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway.

P300 Maintains Primordial Follicle Activation by Repressing VEGFA Transcription.

During the reproductive life, most primordial follicles remain dormant for years or decades, while some are progressively activated for development. Misactivation of primordial follicles can cause ovarian diseases, for example, premature ovarian insufficiency (POI). Our results show that p300 expression increased with primordial follicle activation. Using a p300 inhibitor resulted in premature activation of primordial follicles in cultured mouse ovaries. Conversely, the ratio of primordial follicle activation was markedly decreased upon culturing with the p300 agonist. Furthermore, p300 regulated primordial follicle activation by inhibiting Vegfa transcription in granulosa cells. Additionally, this study was extended to potential clinical applications, showing that short-term treatment with a p300 inhibitor in vitro significantly increased primordial follicle activation in newborn mouse ovaries after dorsal kidney membrane transplantation in female NSG mice. Our results revealed that p300 controls the activation of primordial follicles in mammalian ovaries.

Menstrual Blood-Derived Endometrial Stem Cells Ameliorate Ovarian Senescence by Relieving Oxidative Stress-Induced Inflammation.

Senescence is a degenerative process that occurs with ageing, and in the female reproductive system, senescence occurs earlier in the ovaries than in other tissues and organs, which implies a decrease in oocyte quality and exhaustion of the primordial follicular pool, leading to impaired ovarian function and an inability to maintain normal fertility. Unfortunately, the development of curative and effective treatments for ovarian senescence is still a considerable challenge. Currently, mesenchymal stem cells (MSCs)-based therapies for treating various refractory diseases, especially ovarian dysfunction, have been extensively studied and confirmed. However, the mechanisms by which MSCs improve ovarian senescence are not yet clear. Therefore, in this study, a mouse ageing model was generated via the intraperitoneal injection of a D-galactose (D-gal) solution, and the effects of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on the ovarian follicle count, fibrosis level, and degree of apoptosis were evaluated. Subsequently, an ovarian granulosa cell ageing model was induced with H2O2, and CCK-8 assays, flow cytometry, mitochondrial membrane potential analysis and Western blotting were subsequently performed to further investigate the potential mechanism by which MenSCs ameliorate cellular oxidative damage. Overall, our findings demonstrated that MenSCs treatment can increase the cellular antioxidant capacity by activating the NRF2/HO-1 signalling pathway and further ameliorate the inflammatory ovarian microenvironment, apoptosis and dysfunction in ageing mice. These results provide reliable evidence and support for MenSCs-based therapy for ovarian senescence.

Prediction of menstrual recovery patterns in premenopausal women with breast cancer taking tamoxifen after chemotherapy: an ASTRRA Substudy

BackgroundChemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients.MethodsIn the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels.ResultsThe data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63–13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37–2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation.ConclusionThis model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.

Gonadal changes in children and adolescents with congenital adrenal hyperplasia.

Testicular adrenal rest tumours (TARTs) are a common cause of infertility in males with congenital adrenal hyperplasia (CAH). Ovarian adrenal rest tumours (OARTs) and polycystic ovaries (PCO) can impair ovarian function in female patients with CAH. We aim to detect gonadal changes in children and adolescents with CAH. This study was conducted on 50 CAH patients (30 females and 20 males) with 21-hydroxylase deficiency (21-OHD), with a mean age of 10.35 ± 2.36 years. Testicular ultrasonography and pelvic magnetic resonance imaging (MRI) were done in males and females respectively. Glucocorticoid doses and biochemical data were obtained from the patients' medical records. TARTs were detected in 10/20 male patients (50 %). There was a significant relation between presence of TARTs, body mass index (BMI) standard deviation score (SDS), and bone age (p=0.017 and 0.023; respectively). There was no significant relation between presence of TARTs, laboratory parameters, or treatment received (p>0.05). Of those subjected to genetic analysis, 48 % had I2 splice (c.290-13A/C>G) followed by P30L (c.89C>T) (40.7 %). P30L (c.89C>T) was the most common allele among the patients with TARTs (42.9 %). There was no significant relation between presence of TARTs, the genotype, alleles, or the genotype groups (p>0.05). Only one female patient had radiological evidence of bilateral polycystic ovaries and none had OARTs. The prevalence of TARTs in our study was high (50 %). Screening for TARTs in males with CAH is crucial; however, routine ovarian imaging in CAH females is not indicated unless ovarian dysfunction is present.