Female Health Research Articles

Polystyrene microplastics and di-2-ethylhexyl phthalate co-exposure: Implications for female reproductive health

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats’ reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor β1 (TGF-β1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-β1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

Evaluation of female university students’ knowledge, attitudes, and practices toward human papillomavirus infection and vaccination. Multicenter cross-sectional study

IntroductionHaving good knowledge and a favorable attitude toward human papillomavirus (HPV) and HPV vaccinations is the cornerstone for increasing the use of HPV vaccinations and preventing cervical cancer. The objective of this study was to evaluate the level of knowledge, attitudes, and practices regarding HPV and HPV vaccinations, as well as to identify associated factors among female undergraduate health science students at both the University of Gondar (UoG) and Bahir Dar University (BDU), Amhara, Ethiopia.MethodsInstitutional-based multicenter descriptive cross-sectional study was conducted from June 1, 2023, to July 30, 2023. A multistage sampling technique was used to select 633 female undergraduate health science students, and data were collected using a structured, self-administered questionnaire. The data were coded, entered in Epi-data, and exported to SPSS for analysis. Variables with a P-value < 0.25 in the bivariate analysis were inserted in a multivariate logistic regression model, and those with a P-value of < 0.05 in the multivariate binary logistic regression were considered statistically significant factors for knowledge, attitude, and practice regarding HPV and vaccine against it.ResultsThe study included 600 participants with a mean age of 20.8 ± 0.75 years. Using Bloom’s cutoff points for the KAP study, among the participants, 436 (72.7%) had good knowledge about HPV, whereas 315 (52.5%) had good knowledge about HPV vaccinations. More than half of the participants, 359 (59.8%) heard about HPV vaccinations in Ethiopia. More than half of the participants, 342 (57%) had favorable attitudes toward HPV vaccinations. Only 261 (43.5%) participants believed the HPV vaccine was safe and effective. All participants had never been tested for HPV, and 471 (78.5%) refused to have their samples for regular HPV testing. The factors like ages between 21 and 23 years (AOR, 2.12, 95% CI: 1.22–3.09) and favorable attitudes toward HPV vaccinations (AOR: 1.88; 95%, CI: 1.15–3.41) were associated with the participant’s knowledge about HPV vaccinations. Having good knowledge about the virus (AOR: 1.92; 95%, CI: 1.11–5.88) and its vaccine (AOR:1.60; 95%CI: 1.07–2.47) were factors associated with the attitude of the participants about HPV vaccinations. Additionally, HPV vaccination practice was significantly associated with the attitude of the participants toward HPV vaccinations (AOR: 1.85; 95%CI: 1.15–3.45), knowledge about HPV (AOR: 1.18; 95%CI: 0.55–5.50), and HPV vaccinations (AOR: 1.85; 95%CI: 1.08–2.44).ConclusionThis study revealed that half of the students had good knowledge and a favorable attitude toward HPV vaccinations, but there was poor HPV vaccination practice. There is still a need for continued health education, training, and counseling services for students to strengthen HPV vaccination practices, improve students’ attitudes and knowledge about the benefits of vaccination, and improve counseling abilities against HPV-induced cancer.

Peripheral, but not central, IGF-1 treatment attenuates stroke-induced cognitive impairment in middle-aged female Sprague Dawley rats: The gut as a therapeutic target

Stroke results in immediate sensory or motor disability and increases the risk for long term cognitive-affective impairments. Thus, therapies are urgently needed to improve quality of life for stroke survivors, especially women who are at a greater risk for severe stroke after menopause. Most current research on stroke therapies target the central nervous system; however, stroke also impacts peripheral organ systems. Our studies using acyclic (estrogen-deficient) middle aged female Sprague Dawley rats show that this group not only displays worse outcomes after stroke as compared to adult females, but also has lower levels of the neuroprotective peptide Insulin-like Growth Factor (IGF1) in circulation. Intracerebroventricular (ICV) administration of IGF1 to this group decreases infarct volume and improves sensory motor performance in the acute phase. In this study, we show that, despite this neuroprotection, ICV-IGF1 did not reduce peripheral inflammation or improve post stroke cognitive impairment in the chronic phase. In view of the evidence that stroke induces rapid gut dysfunction, we tested whether systemic delivery of IGF1 (intraperitoneal, IP) would promote gut health and consequently improve long-term behavioral outcomes. Surprisingly, while IP-IGF1, delivered 4 h and 24 h after ischemic stroke, did not reduce infarct volume or acute sensory motor impairment, it significantly attenuated circulating levels of pro-inflammatory cytokines, and attenuated stroke-induced cognitive impairment. In addition, IP-IGF1 treatment reduced gut dysmorphology and gut dysbiosis. Our data support the conclusion that therapeutics targeting peripheral targets are critical for long-term stroke recovery, and that gut repair is a novel therapeutic target to improve brain health in aging females.

Impact of Genital and Non-Genital Psoriasis on Genital Self-Image, Quality of Life, and Sexual Dysfunction in Female Patients.

Psoriasis is a chronic systemic inflammatory disease that affects millions of people worldwide. While its physical manifestations are well-documented, the psychosocial impact of psoriasis, particularly on female patients, is an area of growing concern. Feelings of shame, inferiority, and stigma are common among individuals with psoriasis, and these emotional burdens can be especially pronounced in females, particularly when the genital area is affected. We aimed to shed light on the significance of genital psoriasis on the overall well-being of female patients. This cross-sectional, descriptive comparative study comprised 50 female participants diagnosed with psoriasis: 25 with genital psoriasis, 25 without genital psoriasis, and 25 healthy women matched for age and sex who served as the control group. All participants underwent an assessment of disease severity using the Psoriasis Area and Severity Index in the psoriasis group and completed questionnaires for the assessment of the Female Sexual Function Index (FSFI). Additionally, quality of life was evaluated using the Dermatology Life Quality Index, and the Female Genital Self-Image Scale (FGSIS) was used to assess genital self-image. We found that females with genital lesions, experience a notable decline in sexual health with higher levels of sexual distress compared to healthy individuals. In terms of the six FSFI domains, the psoriatic group scored lower than the control group in all areas, except for pain, which showed a significant increase. Psoriatic females also exhibited a significantly more negative FGSIS compared to the control group, and there was a highly significant difference in FGSIS between females with and without genital psoriasis. Understanding the impact of genital psoriasis on female sexual health and overall quality of life is essential for comprehensive patient care. This research is instrumental in addressing the psychosocial aspects of psoriasis and enhancing patient well-being.

Molecular docking analysis of shatavarins with female hormonal receptors.

Shatavari (Asparagus racemosus) has been used for female health problems since ancient times and is useful for treating various female reproductive problems including menopausal problems, hormonal imbalance, lactation, menstrual issues, and others. Shatavarins, the primary phytoconstituents of Shatavari, have high molecular weights and may interact with hormone receptors. We have conducted a molecular docking analysis for different Shatavarins such as Shatavarin I, Shatavarin IV, Shatavarin VI, Shatavarin VII, Shatavarin VIII, Shatavarin IX, and Shatavarin X with different hormonal receptors such as estrogen alpha, beta, and gamma receptor, progesterone receptor, FSH, and LH receptors. The best docking conformations with the highest docking scores, specific interactions and bond formations, and the most important residues of the receptors were identified and reported. The study was successful in providing an initial comparative insight into the binding efficiencies of the Shatavarins for different female hormonal receptors.

Interconnected microbiomes-insights and innovations in female urogenital health.

The paradigm that the vaginal microbiota is a protective gateway for the urinary and reproductive systems has endured for more than a century and driven decades of probiotic research. Evidence robustly supports the notion that healthy urogenital microbiomes are predominantly colonized by lactobacilli, particularly Lactobacillus crispatus, which can acidify the local environment and protect against urogynecologic pathogen colonization. However, recent studies are beginning to delve deeper into the intricate mechanistic interactions connecting the microbiome, its diverse functional potential, host immunity, pathogens, and the development of urogenital diseases. Leveraging these emerging insights alongside past successes presents promising opportunities for future therapies aimed at enhancing the management of conditions such as bacterial vaginosis, urinary tract infections, bladder pain, urinary incontinence, and beyond.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial

Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. A total of 35 patients received 6×107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No.20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

The Key Role of Vitamin D in Female Reproductive Health: A Narrative Review.

Vitamin D, besides its crucial role in bone health and immune function, has received increased attention in recent years due to its possible impact on many processes related to female reproductive health. Recent research has tried to explain the role played by vitamin D in maintaining adequate hormonal status, fertility, and pregnancy outcomes. Our aim for this narrative literature review was to highlight and explain the mechanisms through which vitamin D status impacts female reproductive health. We believe this represents a very important subject of research, especially due to the increased incidence of infertility nowadays. Further studies are necessary on the association between vitamin D status and female reproductive health in order to fully understand its effects and to reach a consensus regarding vitamin D supplementation as a method to improve fertility status.

T-2 toxin exposure induces ovarian damage in sows: lncRNA CUFF.253988.1 promotes cell apoptosis by inhibiting the SIRT3/PGC1α pathway

T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.

Sub-Chronic Methomyl Exposure Induces Oxidative Stress and Inflammatory Responses in Zebrafish with Higher Female Susceptibility.

The widespread use of carbamate pesticides has raised significant environmental and health concerns, particularly regarding water contamination and the disruption of defense systems in organisms. Despite these concerns, research on the differential impacts of pesticides on male and female organisms remains limited. This study focused on methomyl, investigating sex-specific differences in liver antioxidant defenses and inflammatory response indices in male and female zebrafish after 56 days of exposure to environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings indicate that methomyl exposure significantly increased ROS content in zebrafish livers, inducing oxidative stress and activating enzymatic antioxidant defenses such as SOD, CAT, and GSH-Px activities. Sub-chronic exposure altered the expression of apoptosis-related genes (Bax/Bcl2a and Caspases3a), resulting in liver cell apoptosis in a concentration-dependent manner, with the 0.20 mg/L concentration causing the most severe damage. Additionally, methomyl exposure at environmentally relevant concentrations triggered persistent inflammatory responses in liver tissues, evidenced by increased transcription levels of inflammatory factor genes and the activation of toll-like receptors, heightening susceptibility to exogenous allergens. It is noteworthy that oxidative damage indicators (AST, ROS, MDA) and inflammatory gene expressions (IL-1β, TNF-α) were significantly higher in female livers compared to male livers at 0.10-0.20 mg/L methomyl exposure. Consequently, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms and highlights the need for heightened consideration of the risks posed by environmental endocrine disruptors to female health and safety.

The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight.

Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.

The state of female reproductive health in a city with a large petrochemical complex

Introduction. The demographic situation in the country is characterized by a natural decline in the population, which determines the special importance of the protection of motherhood and childhood. The system of obstetrics largely affects the health status of the population and the future generation. Therefore, the study of the state of obstetrics has a high social significance and is relevant. Purpose of the study. To assess the state of female reproductive health of the population living in a city with a large petrochemical complex. Materials and methods. An analysis of primary digital data characterizing the intensive and extensive indicators of the state of obstetric care in the city of Salavat for 2020 was performed. According to the report of the Ministry of Health of the Republic of Bashkortostan “The state of health of the population and the activities of medical institutions of the Republic of Bashkortostan in 2020” a comparative analysis was carried out. Results. An analysis of the state of obstetric care in the city of Salavat showed that women began to give birth less, they interrupted one third of the onset of pregnancies with abortions. The number of abortions per 1,000 women of childbearing age is 1.5 times higher than in the republic. Over the years, the number of abortions is growing against the background of their decline in the republic. Women who wish to give birth in the vast majority come under the supervision of an antenatal clinic until the 12-week gestation period. The results of the course of pregnancy, childbirth, and the postpartum period, the absence of maternal mortality indicate to a high level of obstetric care. However, he draws attention to the fact that 45.6±1.5% of deliveries and the postpartum period proceeded against the background of complications, among which the most significant were anemia, premature rupture of the amniotic membrane, and violations of labour activity. Every third woman in labour underwent a caesarean section, every fifth - vacuum extraction. The health indicators of the fetus and newborn in the trend in years are improving and more favourable than in the republic as a whole, but 58.9±1.3% of neonates were born sick and fell ill. Mainly in the form of asphyxia during childbirth (18.6±1.2%) and infectious diseases (39.5±4.4%). Preterm infants get sick 2 times more often than full-term ones and the main reason is asphyxia during delivery and respiratory disorders over the perinatal period. Limitations. The analysis of the primary digital values of obstetric care indicators of the forms of federal statistical observation and accounting of medical institutions in Salavat for 2020 was carried out. Conclusion. More favourable health indicators of pregnant women, mothers, fetuses in Salavat in comparison with republican and all-Russian ones indicate to the high-quality, qualified obstetric care. The higher incidence of respiratory diseases in infants during the first year of life living in a city of large petrochemistry determines the need for special in-depth studies.

Clinical Spectrum of Long COVID: Effects on Female Reproductive Health.

The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on the impact of SARS-CoV-2 on the menstrual cycle, ovarian function, fertility, and overall gynecological health. This study emphasizes the role of angiotensin-converting enzyme receptors in viral entry and the subsequent tissue-specific pathological effects. It also explores the potential influence of long COVID on hormonal balance and immune responses, contributing to menstrual irregularities and impaired ovarian function. The findings indicate a higher prevalence of long-term COVID-19 among women, highlighting the substantial implications for reproductive health and the need for sex-sensitive longitudinal studies. Enhanced surveillance and targeted research are essential to develop effective interventions that prioritize women's reproductive well-being following SARS-CoV-2 infection. This review advocates for a sex-informed approach to ongoing COVID-19 research and healthcare strategies, aiming to provide up-to-date and pertinent data for healthcare providers and the general public, ultimately improving outcomes for females affected by long COVID.

Evaluation of urban–rural difference in breast cancer mortality among Chinese women during 1987–2021: A hierarchical age-period-cohort analysis

BackgroundBreast cancer mortality varies in urban and rural areas in China. Studies have reported urban–rural difference across time period, however, the evaluation on urban–rural differences in age and birth cohort effects is limited. Our aim was to quantitatively assess urban–rural disparities in age, period and cohort effects in breast cancer mortality in China. MethodsWe collected age-specific breast cancer mortality rates for urban and rural females aged 20–84 years from 1987 to 2021. Hierarchical age-period-cohort (HAPC) models were used to evaluate the effect of area (urban, rural) on breast cancer mortality and investigate urban–rural differences in age, time period and birth cohort effects. ResultsWe found a significant area (urban, rural) effect on breast cancer mortality in that rural females had a lower mortality risk than urban females [−0.25 (95 % confidence interval (CI): −0.32, −0.17)]. Age trajectories of mortality based on the HAPC model showed nonlinear trends with adjustment for area variable. The urban–rural difference in age effect appeared to be divergent with age, and urban women had higher mortality risk in the senior age group. The urban–rural difference in birth cohort effect indicated a reversal around the birth cohort group of 1962–1966, after which rural females had a higher mortality risk than urban females. ConclusionThe area (urban, rural) could affect breast cancer mortality among women, and the effect of urban–rural difference varies with age and birth cohort. To promote the health of urban and rural females, the gap between urban and rural areas should be shorten.

Elucidating the reproductive toxicity mechanisms in female zebrafish: A transcriptomic study of lifetime tris(2-chloroethyl) phosphate exposure

Tris(2-chloroethyl) phosphate (TCEP), emerging as a predominant substitute for brominated flame retardants (BFRs), is now increasingly recognized as a prevalent contaminant in aquatic ecosystems. The extent of its reproductive toxicity in aquatic species, particularly in zebrafish (Danio rerio), remains insufficiently characterized. This study subjected zebrafish embryos to various concentrations of TCEP (0, 0.8, 4, 20, and 100 μg/L) over a period of 120 days, extending through sexual maturation, to assess its impact on female reproductive health. Notable reductions in body weight (0.59- and 0.76-fold) and length (0.71- and 0.77-fold) were observed at concentrations of 20 and 100 μg/L, with a concomitant decrease by 0.21- to 0.61-fold in the gonadal somatic index across all treatment groups. The reproductive output, as evidenced by egg production and hatchability, was adversely affected. Histopathological analysis suggested that TCEP exposure impedes ovarian development. Endocrine alterations were also evident, with testosterone and 11-ketotestosterone levels significantly diminished by 0.38- and 0.08-fold at the highest concentration tested, while 17β-estradiol was elevated by 0.09- to 0.14-fold in all exposed groups. Transcriptomic profiling illuminated numerous differentially expressed genes (DEGs) integral to reproductive processes, including hormone regulation, neuroactive ligand-receptor interactions, oocyte meiosis, and progesterone-mediated maturation pathways. Collectively, these findings indicate that lifelong exposure to TCEP disrupts ovarian development and maturation in female zebrafish, alters gene expression within the hypothalamic-pituitary-gonadal axis, and perturbs sex hormone synthesis, culminating in pronounced reproductive toxicity.

The shared mechanism and potential diagnostic markers for premature ovarian failure and dry eye disease

Premature ovarian failure (POF), which is often comorbid with dry eye disease (DED) is a key issue affecting female health. Here, we explored the mechanism underlying comorbid POF and DED to further elucidate disease mechanisms and improve treatment. Datasets related to POF (GSE39501) and DED (GSE44101) were identified from the Gene Expression Omnibus (GEO) database and subjected to weighted gene coexpression network (WGCNA) and differentially expressed genes (DEGs) analyses, respectively, with the intersection used to obtain 158 genes comorbid in POF and DED. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of comorbid genes revealed that identified genes were primarily related to DNA replication and Cell cycle, respectively. Protein–Protein interaction (PPI) network analysis of comorbid genes obtained the 15 hub genes: CDC20, BIRC5, PLK1, TOP2A, MCM5, MCM6, MCM7, MCM2, CENPA, FOXM1, GINS1, TIPIN, MAD2L1, and CDCA3. To validate the analysis results, additional POF- and DED-related datasets (GSE48873 and GSE171043, respectively) were selected. miRNAs-lncRNAs-genes network and machine learning methods were used to further analysis comorbid genes. The DGIdb database identified valdecoxib, amorfrutin A, and kaempferitrin as potential drugs. Herein, the comorbid genes of POF and DED were identified from a bioinformatics perspective, providing a new strategy to explore the comorbidity mechanism, opening up a new direction for the diagnosis and treatment of comorbid POF and DED.

Hsa_Circ_002144 Promotes Glycolysis and Immune Escape of Breast Cancer Through miR-326/PKM Axis.

Background: Breast cancer is a leading cause of cancer-related deaths in women worldwide, posing a significant threat to female health. Therefore, it is crucial to search for new therapeutic targets and prognostic biomarkers for breast cancer patients. Method: Bioinformatics analysis, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization (FISH) were employed to investigate the expression of hsa_circ_002144 in breast cancer. Transwell assay, Western blotting, and cell viability assay were utilized to assess the impact of hsa_circ_002144 on the proliferation, migration, and invasion of breast cancer cells. Additionally, a mouse model was established to validate its functionality. Flow cytometry, WB analysis, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, exosomes isolation, and co-culture system were employed to elucidate the molecular mechanism underlying macrophage polarization. Result: we have discovered for the first time that hsa_circ_002144 is highly expressed in breast cancer. It affected tumor growth and metastasis and could influence macrophage polarization through the glycolytic pathway. Conclusion: This finding provides a new direction for breast cancer treatment and prognosis assessment.

O-174 Marginal gains: can small actions in the ART lab improve the environmental impact of medically assisted reproduction?

Abstract Marginal gains can small actions in the ART laboratory improve the environmental impact of medically assisted reproduction? (Invitation) Study question Is it possible to reduce the environmental impact of assisted reproductive technology (ART) laboratories while maintaining quality and safety? Summary answer While individual interventions may yield modest results, their cumulative effect on a wider scale can lead to substantial reductions in resource consumption and emissions over time without compromising treatment outcomes or patient/staff safety. What is known already According to the World Health Organisation (WHO) the change in global climate is one of the gravest threats facing humanity, with pregnant women, new-born and child health considered highly vulnerable. In recent years growing evidence has linked climate change, air pollution, pollutant exposure and microplastics to compromised male and female reproductive health and even spontaneous and in vitro fertilisation (IVF) outcomes. Ironically, the healthcare industry is a major contributor of greenhouse gas emissions, and the rapidly increasing utilisation of ART has raised concerns regarding its environmental footprint. A field primarily driven by highly specialised, energy-intensive laboratory processes, continuous monitoring of hormone testing, single-use consumables and large amounts of waste; the quest for bringing awareness to sustainable practices within ART laboratories is critical, not just for the planet, but for our patients and future generations. Study design, size, duration Alongside a comprehensive review of existing literature, a panel of international professionals and enthusiasts within reproductive medicine, law and environmental science convened in a green conferencing format to discuss key environmental challenges associated with ART and explored potential avenues for enhancing sustainability in the laboratory. A survey and interviews with stakeholders also took place to understand current attitudes and provide real-time social, economic and environmental examples of sustainability in ART laboratories. Main Results I will present a roadmap for sustainability in the IVF laboratory so far. A selection of actions which result in marginal gains within the ART laboratory include but are not limited to: Participate in a ‘green certification’ programme specifically tailored to the IVF laboratory and consider forming a ‘green team’ Aim for energy efficiency, renewable energy, preventive maintenance and consider plug load of non-essential equipment for cost savings. Consider widening operating ranges for temperature and humidity, air circulation changes and HVAC design where possible for energy savings of 15–30% Correct waste management can result in &amp;gt; 30% reduction in clinical waste alongside €11,600 annual savings, with focus on prevention of unnecessary consumables (dishes, media), reducing use of plastics and other single-use items to the extent that is possible and safe, and reusing where appropriate (e.g., training vitrification straws). Adopt electronic platforms for consents/laboratory paperwork; avoiding the use of &amp;gt; 40 pages per cycle in the UK. Reuse packaging materials (cold gel packs, bubble wrap) or form partnerships with local businesses who can reuse. Manage inventory carefully, asking for products with longer expiry dates, and consolidate purchase order to minimise frequency. Minimise liquid nitrogen loss during routine activities and consider batching samples for cryo-transport to minimise frequency of shipments. Limitations Every country, region and laboratory is different and will have their own myriad of regulatory constraints and industry standards to adhere to. This may present barriers to the adoption of certain sustainability measures in ART laboratories and is therefore imperative to seek local guidance first. Wider implications of the findings The carbon footprint of ART extends beyond the laboratory and into the supply chain, encompassing transportation, pharmaceutical production, and waste disposal processes. In this way a holistic approach is necessary, with the need for partnerships between fertility clinics, manufacturers, and regulatory bodies continuously working together to drive the development and adoption of sustainable practices and technologies across the entire ART field.

O-038 Impact of maternal aging on the DNA repair landscape in mouse oocytes

Abstract Study question How does maternal aging impact DNA damage accumulation and DNA repair capacity in mammalian oocytes? Summary answer Age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in DNA repair capacity. What is known already Oocyte loss occurs progressively from birth and accelerates as women approach their mid-30s, posing a significant challenge to female reproductive health. Recent studies have highlighted the role of the DNA repair response in driving ovarian ageing and oocyte loss. Aged oocytes accumulate elevated levels of DNA damage. Unless repaired, persistent DNA damage activates DNA repair checkpoints, causing the elimination of defective oocytes. Although we know DNA double-strand breaks (DSBs) in oocytes increase with maternal age, surprisingly, little is known about why this damage is not repaired efficiently. Study design, size, duration Oocytes were isolated from ovaries of 8 weeks or 68-86-week-old CD1 mice, which correspond to reproductively young and old females respectively. Over 600 and 1000 oocytes from aged any young females were used to analyse DNA damage levels, DNA repair effciency, DNA repair compartments and for other live assays. Participants/materials, setting, methods DNA damage was induced in CD1 oocytes from young and aged mice using neocarzinostatin. Levels of DNA damage and DNA repair proteins were quantified using immunofluoresnce confocal/STED microscopy. High-resolution light sheet microscopy was used to perform live imaging of dynamics of DNA damage foci and chromosome segregation during meiosis. Main results and the role of chance Our work demonstrates that aged oocytes have a lower DNA repair capacity and reduced mobility of DNA damage sites compared to young oocytes. We further show that incomplete DNA repair results in defective chromosome integrity and partitioning, thereby compromising oocyte quality. To investigate the causes of the age-related decline in DNA repair, we systematically studied the localization and abundance of several DNA repair proteins in oocytes from young and aged mice. We found that DNA repair proteins localized in spatially distinct DNA repair compartments in oocyte nuclei, that form during the late stages of oocyte growth, accompanied by changes in the activity of DNA repair pathways. Several DNA repair proteins, their corresponding compartments, and their response to DNA damage were altered in aged oocytes. Lastly, we demonstrate that age-related cohesin loss increases DNA damage levels and reduces DNA repair capacity. We hypothesize that cohesin dissociation with maternal ageing may make chromosomes prone to accumulate DNA damage without proper DNA repair. Thus, age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in reproductive potential. Limitations, reasons for caution Neocarzinostatin, a radiomimetic drug used to induce DNA DSBs in mouse oocytes in vitro, may not fully represent sources of DNA damage during aging. The CD1 mouse model and ages were selected to recapitulate equivalent advanced maternal age in women. Further investigation is needed to confirm these findings in humans. Wider implications of the findings Overall, we propose that altered DNA repair machinery and cohesin loss contribute to persistent DNA damage and reduced DNA repair capacity in aged oocytes, which can cause chromosome defects and fragmentation, and eventually trigger oocyte death, thereby accelerating the loss of female fertility. Trial registration number Not Applicable

O-220 Ovarify: a deep learning model for automatic calculation of ovarian morphological features in pelvic ultrasonography

Abstract Study question Can a deep learning model accurately characterize ovarian features on pelvic ultrasounds? Summary answer We developed a deep learning model, Ovarify, that can accurately classify and segment ovarian features on pelvic ultrasounds. What is known already Ovarian morphology, as detected using pelvic ultrasonography, is used widely in the assessment of gynecological health. Morphological metrics such as ovarian volume and antral follicle count have known diagnostic and prognostic value for a variety of gynecological outcomes, ranging from risk for ovulatory disorders to likelihood of response to assisted reproductive technologies. However, a lack of standardization in the interpretation of ovarian features, and the time-intensive nature of validated image analysis techniques (such as 2D grid analysis), limits their utility in clinical practice. Deep learning provides an opportunity to overcome these limitations. Study design, size, duration The training dataset for the model comprised 426 3D pelvic ultrasounds obtained using the GE Voluson ultrasound platform, yielding 56,538 individual frames with potential ovarian content. In addition, a similarly collected validation dataset consisted of 95 ultrasounds, yielding 11,304 frames. The held-out test set comprised 107 ultrasounds with 14,767 frames. All frames were manually labeled with the associated 2D ovarian contour, and 163 of the ultrasounds had an associated ovarian volume label. Participants/materials, setting, methods Ovarify consists of two stages: 1) a lightweight classifier that labels ultrasound frames as either positive or negative (having or not having ovarian content) and 2) a subsequent U-Net-inspired segmentation module with an Xception backbone and attention-based decoder that segments the ovary and antral follicles in all frames previously classified as positive. Classification performance was evaluated using F1-score and area under the receiver operating characteristic curve (AUROC). Segmentation performance was evaluated using the Jaccard index. Main results and the role of chance For the classification stage, Ovarify achieved an AUROC of 0.980±0.002 and 0.976±0.004 on the training and validation sets, respectively. On the held-out test set, the model achieved an AUROC of 0.971±0.005. In addition, the model achieved an F1-score of 0.825±0.006, 0.810±0.013, and 0.784±0.014 on the training, validation, and held-out testing sets, respectively. The high AUROC and F1-scores across both seen and unseen datasets support a high-performing classifier. In the segmentation stage, Ovarify reached a median Jaccard index of 0.815±0.004 on the unseen test set when tasked with segmenting the ovary, and a median Jaccard index of 0.657±0.018 on the unseen test set when segmenting antral follicles. High agreement between the ground truth ovary and follicle labels and the predicted segmented regions increases confidence in the downstream morphological analysis. For example, the Pearson correlation coefficient between the Ovarify-calculated ovarian volume and manually-validated ovarian volume was 0.813, indicating that an automatic ovarian volume calculation highly aligns with the ground truth. Ovarify was able to provide predictions in under one minute for the entirety of the held-out test set. Limitations, reasons for caution Ovarify was trained on images generated by the GE Voluson platform and has not been evaluated for generalizability across ultrasound images generated using machines whose output does not match the DICOM format standard. Wider implications of the findings The model developed is relevant for automatically calculating ovarian morphological features from pelvic ultrasounds. This approach has implications in removing user-specific bias and error when calculating biomarkers associated with female reproductive health, including but not limited to ovulatory disorders such as polycystic ovary syndrome (PCOS). Trial registration number not applicable