Reproductive Disorders Research Articles

Features of reproductive function and IVF programs in patients with overweight and obesity

Obesity is a chronic multifactorial heterogeneous disease characterized by high prevalence, progressive increase in morbidity, high cardiometabolic risk. The prevalence of obesity is increasing from year to year and does not tend to decrease. Up to 60% of women of reproductive age are overweight, and a quarter of them are obese. In addition to cardiovascular pathology, type 2 diabetes, gastrointestinal diseases, oncological processes, obesity can affect the reproductive function of women, reduce fertility and be an independent cause of infertility, as well as reduce the effectiveness of assisted reproductive technology programs. This paper analyzes studies on the problem of reproductive system disorders, the effectiveness and safety of assisted reproductive technology programs in patients with overweight / obesity. The review includes data from foreign and domestic articles in the Pubmed, Elsevier, Cochrane Library, e_library databases published over the past 10 years. As a result of the analyzed publications, it was concluded that the implementation of IVF programs in patients with overweight/obesity presents certain difficulties at each stage of the program: the duration and cost of ovarian stimulation increases, the number and quality of the obtained oocytes and embryos decreases, the displacement of the “implantation window” is more often noted, decreased endometrial receptivity, which together causes a decrease in the pregnancy rate (PR) in this category of patients. It should be noted that in women with visceroabdominal obesity, with more pronounced metabolic abnormalities – dyslipidemia, carbohydrate metabolism disorders, reproductive disorders are expressed to a greater extent than in patients with a more favorable femoral phenotype type of obesity, which requires an individual approach to the treatment of infertility using IVF methods depending on the clinical and etiopathogenetic category of patients.

Establishment of a mouse model of ovarian oxidative stress induced by hydrogen peroxide

IntroductionOxidative stress, resulting from environmental changes, significantly affects female fertility. Developing a mouse model to study oxidative stress lays the groundwork for research into human reproductive health and livestock fertility.Materials and methodsIn this study, we established and evaluated an oxidative stress model by administering hydrogen peroxide (H2O2) to mice. ICR mice of similar age (7–8 weeks old) and average body weight (31.58 ± 1.12 g) were randomly assigned to four groups (A, B, C, and D). Group A served as the control and was injected with a saline solution, while groups B, C, and D received saline solutions containing 0.75%, 1.50%, and 3.0% H2O2, respectively, over one week. We measured the body weights of all mice before and after the experimental period.Results and discussionOur findings showed that the average body weight of mice in groups A and B increased, while groups C and D experienced weight loss. Group C showed a significantly lower average weight gain compared to groups A and B, and group D exhibited an even more pronounced reduction in weight gain. Although group D had a high mortality rate, there was no significant difference in mortality rates among groups B, C, and D. Serum malondialdehyde (MDA) content increased with higher concentrations of H2O2, with a significant difference noted between groups C and A. Catalase (CAT) activity in group B was significantly higher than in group A, while superoxide dismutase (SOD) activity in group C was notably elevated compared to groups A and B. Conversely, glutathione peroxidase (GSH-Px) activity in group C was significantly lower than in both group A and group B. Hematoxylin and eosin (HE) staining revealed changes in ovarian morphology and follicle dynamics. The percentage of atretic follicles in group C was significantly higher than in the control group, and group D had a significantly lower total number of healthy follicles compared to the untreated group. Increased H2O2 content resulted in a reduction of ovary size and an irregular appearance in group D.ConclusionBased on our findings, treatment with 1.50% H2O2 effectively established an oxidative stress model in mice within 1 week. This model serves as a valuable reference for future clinical studies on oxidative stress and reproductive disorders in female animals and humans.

The effect of rapamycin treatment on mouse ovarian follicle development in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model.

Polycystic ovary syndrome (PCOS) is a complex reproductive and endocrine disorder affecting 5-10% of women of reproductive age, but the pathophysiology of PCOS still remains unknown. Here, the aim of our study was to analyze the effects of rapamycin treatment that may regulate impaired hormonal levels and folliculogenesis in dehydroepiandrosterone (DHEA)-treated PCOS mouse. We hypothesized that rapamycin may ameliorate the negative effects of PCOS in DHEA-induced PCOS mouse model. The target of rapamycin (TOR) gene product is a serine/threonine kinase that has been implicated in the control of cell growth, proliferation and autophagy, and rapamycin is a potent inhibitor of mTORC1 pathway. In this study, for the first time, mTORC1 and activation products are presented at protein and mRNA levels after rapamycin treatment in DHEA-induced PCOS mouse ovary. We showed that rapamycin treatment may regulate follicular development, hormonal levels and provide ovulation in DHEA-induced PCOS mouse. Additionally, we assessed decreased primordial follicle reserve, increased number of primary and secondary follicles, corpus luteum structure forms again after 10 days of rapamycin treatment. This study presented here suggests rapamycin treatment regulates hormonal phenotype and folliculogenesis in the ovary and also mTOR signalling pathway in granulosa cells of DHEA-induced PCOS mouse ovary which may have potential to attenuate understanding the mechanism of dominant follicle selection and anovulatory infertility.

Causal relationship between inflammatory cytokines and polycystic ovary syndrome: a bidirectional mendelian randomization study.

Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS.

The associations between exposure to mixed environmental endocrine disruptors and sex steroid hormones in men: a comparison of different statistical models

In recent years, worldwide fertility rates have continued to decrease. Humans are frequently exposed to a combination of environmental endocrine disruptors, which can cause male reproductive disorders. The study employed three distinct analytical models to examine the correlation between exposure to a combination of 25 chemicals and sex steroid hormone levels in adult males. This involved evaluating 12 chemicals and their metabolites from personal care and consumer products, as well as 13 metabolites linked to phthalates and plasticisers. The study analysed 25 chemicals and 3 measured sex steroid hormone outcomes, as well as two calculated hormonal outcomes (free androgen index, TT/E2 ratio) in 1262 adult men who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 in the United States. The study employed several statistical methods to estimate the relationships between single chemicals or chemical blends and sex hormones. These methods included linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine (BKMR) regression. The results of the linear regression analysis indicate that chemical exposure has a negative correlation with E2, TT, and FAI, and a positive correlation with SHBG and TT/E2. The mixture effect analyses using the WQS and BKMR models further confirmed that BP3, MECPP, and MECOP were the most highly weighted chemical mixtures. The analyses also suggested that there were differences in the effects of different concentrations of EDCs on sex steroid hormones. Exposure to environmental endocrine-disrupting chemicals (EDCs) has been found to have a negative correlation with estradiol and total testosterone, as well as FAI. Conversely, this exposure has been found to have a positive correlation with sex hormone binding globulin and the TT/E2 ratio. The study also revealed differences in the effects of different concentrations of EDCs.

Epidemiological surveillance of Neospora caninum in sheep (Ovis aries) and European mouflon (Ovis aries musimon) in southern Spain.

Neospora caninum is a protozoan with a facultative heteroxenous life cycle, with canids as the definitive hosts and other mammals, mainly ruminants, acting as intermediate hosts. This parasite is recognized as one of the major abortifacient pathogens in cattle. Although reproductive disorders have also been reported in other domestic and wild ruminants, epidemiological data on N. caninum in ruminant species other than cattle is still limited. Here, we evaluate the seroprevalence and risk factors associated with N. caninum exposure in sheep (Ovis aries) and European mouflon (Ovis aries musimon) in southern Spain. Serum samples from 390 sheep and 387 free-ranging mouflons were tested for antibodies against N. caninum using in-house time-resolved fluorescence immunoassay based on NcGRA7 as a recombinant antigen. The individual seroprevalence was 26.2% (95%CI: 22.0-30.7) in sheep and 5.7% (95%CI: 3.8-8.5) in mouflons. At least one seropositive animal was detected in all the 26 sheep farms (100%) and in eight of the 18 (44.4%) hunting estates sampled. The presence of dogs on the farm (≥3) and the sheep breed (purebred) were potential risk factors associated with exposure to N. caninum in sheep. Our results indicate a high circulation of N. caninum in sheep farms in southern Spain. Control measures should be implemented to limit the exposure to this protozoan in sheep flocks. Although we have confirmed for the first time the presence of anti- N. caninum antibodies in European mouflon in Spain, and, despite the relatively low seroprevalence found, the impact of this parasite on mouflon populations should be further studied.

Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products.

This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review since most studies that have developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of EDCs in humans and animals at different developmental periods. Various food bioactive compounds (FBCs) such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs) present antioxidant, anti-inflammatory, anti-tumor, and other biological properties with the potential to reduce of deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies produced in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). Additionally, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction since there is a lack of studies with females.

The bta-miR-22-3p can alleviate LPS-induced inflammatory response in yak endometrial epithelial cells by targeting KSR2

Bovine endometritis is a common reproductive system disease in dairy cows that leads to decreased milk production and reproductive performance, causing significant economic losses for farmers. Research has shown that microRNAs (miRNAs) play a significant role in regulating the expression of biological genes and are closely related to the occurrence of inflammation, including bta-miR-22-3p. However, the specific molecular mechanisms by which miRNAs regulate bovine endometritis remain unclear. To investigate the regulatory mechanism of bta-miR-22-3p in yak endometritis, uterine tissues were collected from three healthy bos grunniens and three bos grunniens with endometritis, approximately 21 days postpartum. Various methods were employed, including real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF). The results demonstrated that overexpression of bta-miR-22-3p led to a significant decrease (P<0.05) in factors related to the mitogen-activated protein kinase (MAPK) signaling pathway and associated inflammatory factors, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (P38), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Furthermore, dual-luciferase assays confirmed that the kinase suppressor of the Ras 2 (KSR2) gene is a downstream target of bta-miR-22-3p. Overexpression of bta-miR-22-3p inhibited the expression of KSR2. When KSR2 was inhibited, the levels of MAPK signaling pathway-related factors and inflammation also significantly decreased(P<0.05). Thus, bta-miR-22-3p suppresses the activation of the MAPK signaling pathway through the inhibition of KSR2, resulting in a reduction of inflammatory factors. In conclusion, this study demonstrated that bta-miR-22-3p targets the KSR2 gene to alleviate LPS (Lipopolysaccharide)-induced inflammatory damage.

Marfan syndrome is associated with increased risk for gynecologic disorders and maternal complications.

To determine whether patients with Marfan syndrome are at an increased risk for reproductive disorders. This retrospective cohort study was conducted using the US collaborative network on the TriNetX research network of health care organizations. We included female patients aged 18-44 and identified a cohort of 4347 patients with Marfan syndrome (ICD-10 Q87.4). Our control cohort consisted of 16,424,990 patients without a diagnosis of Marfan syndrome or Ehlers-Danlos syndrome (ICD-10 Q79.6). The primary outcomes included gynecologic diagnoses such as dysmenorrhea and endometriosis, and our secondary outcomes included urogynecologic, fertility, and obstetric outcomes, all identified by ICD-10 codes. We conducted a relative risk analysis with a p-value of <0.05 considered significant. Patients with Marfan syndrome were at an increased risk for pelvic and perineal pain, dysmenorrhea, abnormal uterine bleeding, endometriosis (all p <0.0001), dyspareunia (p =0.0009), leiomyoma (p =0.0076), polyp of female genital tract (p =0.016), urinary incontinence (p <0.0001), female genital prolapse (p =0.0006), fertility testing (p =0.0075), cesarean delivery (p =0.0003), gestational hypertension (p =0.0012), and pre-eclampsia (p =0.0024) compared to the control group following an adjusted, matched comparison. Patients with Marfan syndrome have an increased risk of numerous reproductive disorders and obstetric complications compared to patients without this diagnosis.

Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review

Oxidative stress is an imbalance between reactive oxygen species production and antioxidant defense that can lead to reproductive disorders and poor pregnancy outcomes. Environmental pollution under climate change is involved in reactive oxygen species formation and may cause various dysfunctions of the reproductive system. Oxidative stress is a widespread factor that affects the physiology of the male and female reproductive systems, leading to high levels of DNA damage and infertility. Miscarriage, preeclampsia, and premature birth are all linked to oxidative stress. Environmental pollution induces excesses of oxidative stress by expanding ROS generation or overwhelming the physiological responses of the antioxidant defense system. This increases cellular damage, inflammation, and the development of numerous diseases. Here, we present a brief outline of the physiological and developmental roles that oxidative stress plays during pregnancy. We also offer some insights into the underlying mechanisms that have been put forth, which culminate in a summary of the harmful effects of oxidative stress that have an environmental origin in pregnancy-related complications. The current work may motivate the design of more focused wellbeing measures in order to prevent and promote human health and anticipate unfavorable pregnancy outcomes.

Elevated RBP4 in Subclinical Ketosis Cows Inhibits Follicular Granulosa Cell Proliferation and Steroid Hormone Synthesis

The mechanism by which subclinical ketosis (SCK) causes postpartum reproductive disorders in dairy cows remains unclear. In this study, cows within the day 14 to 21 postpartum period were categorized into the SCK group or the control group. Subsequently, they were monitored until 45 d to 60 d postpartum and divided into the SCK anestrus group (SCK-AE, n = 12) and the control estrus group (C-E, n = 12). In comparison to the C-E group, the RBP4 and p-AKT of the SCK-AE group exhibited increased levels in serum, liver, and ovaries. In the in vitro experimental cultivation of granulosa cells (GCs), after adding RBP4, cell proliferation, steroid hormone secretion and synthesis, and GLUT4 secretion were inhibited, and cell apoptosis was exacerbated. After silencing STRA6 (RBP4 receptor), cell proliferation and steroid hormone secretion and synthesis, as well as the inhibition of GLUT4, were alleviated, and the situation of cell apoptosis also improved. The SC79 activator could promote the phosphorylation of AKT, thus alleviating the increased cell proliferation, steroid hormone secretion and synthesis, GLUT4 inhibition, and apoptosis rate in cow GCs induced by RBP4 stimulation. Our research indicates that elevated RBP4 levels in SCK cows inhibit the proliferation, apoptosis, and steroid hormone synthesis of GCs through the STRA6 receptor and the PI3K/AKT pathway.

U. Parvum serovars exhibit distinct pathogenicity in Chinese women of childbearing age: a multicentre cross-sectional study

BackgroundUreaplasma spp. can be classified into different serovars. It is unknown whether distinct serovars are associated with clinical signs and symptoms.MethodsWe conducted a multicentre cross-sectional study. U. parvum serovars were identified on the basis of their multiple-banded antigen (MBA) genes. After adjusting for demographic variables and other reproductive tract infections, the odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the impact of U. parvum serovars on clinical symptoms.ResultsAmong 5,277 individuals, U. parvum serovars 3 and 6 were the most prevalent serovars (17.9% and 16.0%, respectively). Potential confounders, such as age, body mass index (BMI), ethnicity, education level, contraceptive methods, number of sexual partners, gravidity, parity, and other sexually transmitted infections (STIs) that are associated with clinical symptoms (P < 0.1) were adjusted for in the univariate analysis. U. parvum serovar 14 was strongly positively associated with certain clinical symptoms, including redness and swelling of the vaginal wall (crude OR: 3.53, 95% CI: 1.92–6.49; adjusted OR: 5.21, 95% CI: 2.56–10.58), cervical bleeding and swelling (crude OR: 3.89, 95% CI: 2.38–6.36; adjusted OR: 7.37, 95% CI: 3.82–14.23), and cervical ectropion (crude OR: 2.08, 95% CI: 1.25–3.45; adjusted OR: 3.04, 95% CI: 1.60–5.74). In contrast, U. parvum serovar 3 was negatively associated with a variety of clinical symptoms, whereas no correlations were detected between U. parvum serovars 1and 6 with clinical symptoms.ConclusionsDifferent U. parvum serovars exhibit distinct correlations with clinical symptoms, suggesting that U. parvum serovars are pathogenically heterogeneous and that further differentiation of serovars may be necessary.Trial registrationThe study was registered with ClinicalTrials.gov (https://www.clinicaltrials.gov; ID: NCT04694495; Registration Date: 2021–01-05).

Experimental and Numerical Investigations of Surface-Enhanced Raman Scattering (SERS) Sensors for Trace Mancozeb Detection: A Step Toward the Prevention of Reproductive Disorders Caused by this Hazardous Substance

Experimental and Numerical Investigations of Surface-Enhanced Raman Scattering (SERS) Sensors for Trace Mancozeb Detection: A Step Toward the Prevention of Reproductive Disorders Caused by this Hazardous Substance

First detection of multidrug-resistant and toxigenic Pasteurella aerogenes in sow vaginal discharge: a novel threat to swine health in Thailand

Pasteurella aerogenes has been implicated in reproductive disorders in sows, yet its prevalence and characteristics in vaginal discharge are not well understood. This study aimed to detect P. aerogenes in sow vaginal discharge samples and investigate its antibiotic resistance profile, toxin genes, and toxicity. P. aerogenes was isolated from 40% (8/20) of samples. Antimicrobial susceptibility testing revealed universal resistance to amoxicillin-clavulanate (4:1), with 87.5% of isolates also resistant to oxytetracycline, amoxicillin, ceftriaxone, and enrofloxacin. The colistin resistance gene mcr-2 was detected in 75% of isolates, while class 1 integron (int1) was found in 12.5%. The pax toxin gene cluster was present in 75% of isolates. Toxicity assays using Panagrellus redivivus demonstrated dose-dependent effects of P. aerogenes supernatant containing pax toxins. This study represents the first report of P. aerogenes isolation from sow vaginal discharge in Thailand. The high prevalence of antibiotic resistance, presence of the mcr-2 gene, and toxicity of pax toxin-positive isolates suggest that P. aerogenes may be an underestimated factor in swine reproductive health. These findings highlight the need for further investigation into the role of P. aerogenes in sow reproductive disorders and its potential impact on swine production.

Ethnopharmacological insights: hyperoside from Marsdenia latifolia (Benth.) K.Schum. mitigates reproductive toxicity in male Wistar rats induced by manganese exposure

This study provides novel findings on the ameliorative effect of hyperoside isolated from Marsdenia latifolia leaves (HIGLL) in reproductive health challenged by manganese toxicity. The study investigated the efficacy of HIGLL on male fertility in rats exposed to manganese chloride (MnCl2). The rats received either MnCl2 (30 mg/L) or in combination with HIGLL (100 mg/kg or 200 mg/kg). MnCl2 reduced fluid intake, organ-body weight, body weight; sperm count, sperm viability, sperm density, sperm motility, semen viscosity, daily sperm production, testicular sperm number; testosterone, follicle-stimulating and luteinising hormones, oestradiol, testosterone/oestradiol ratio; G6PDH, ALP, glucose, NO, acid phosphatase, sialic acid, 17-β-HSD, superoxide dismutase, CAT, GST, GSH, and T-SH without modifying the semen pH and volume, while it correspondingly raised the abnormalities associated with morphology of sperm cells in head, neck, and tail; H2O2 and lipid peroxidation levels. HIGLL abrogated the damaged histoarchitecture of the testes and epididymis caused by MnCl2. HIGLL can serve as a therapeutic agent in the management of male reproductive disorders related to oxidative stress and endocrine disruption.

Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome.

What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS? We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS. PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does. Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses. PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting. MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity. The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001. There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis. The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS. This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest. N/A.

Seroepidemiology of Coxiella burnetii in Domestic and Wild Ruminant Species in Southern Spain

The European Food Safety Authority has recently listed Q fever as a priority for setting up a coordinated surveillance system. Although Spain is the country with the highest human incidence of the disease in the European Union, updated data on Coxiella burnetii in ruminants are still limited. A total of 780 serum samples from small ruminants and 605 sera from wild ruminants were collected in the Mediterranean ecosystems of southern Spain during the period 2015–2023. Anti-C. burnetii antibodies were detected using a commercial indirect ELISA. The overall individual seroprevalence in the small ruminants was 49.1% (383/780; 95% CI: 45.6–52.6). Antibodies against C. burnetii were identified in 40.0% (156/390) of sheep and in 58.2% (227/390) of goats. At least one seropositive animal was observed in all sheep (100%) and in 92.3% of goat flocks. The species (goat) and the existence of reproductive disorders in primiparous females were potential risk factors for C. burnetii exposure in small ruminant farms. In the wild ruminants, the overall seroprevalence against C. burnetii was 1.5% (9/605; 95% CI: 0.8–2.8). Anti-C. burnetii antibodies were found in 1.8% (2/110) of mouflon, 1.5% (6/390) of red deer, and 1.0% (1/105) of Iberian ibex. The high exposure of the small ruminants to C. burnetii, particularly in goats, detected in the present study is of animal and public health concern. Our results denote that wild ruminants only play a minor role in the epidemiology of this bacterium in southern Spain and suggest an independent epidemiological cycle of C. burnetii in domestic and wild ruminant species in the study area.

Women's self-reported symptoms of reproductive tract infection, medical consultations, and factors influencing them in less developed regions: perimenopausal and older women in need of urgent attention.

Reproductive tract infections (RTIs) represent a critical public health concern impacting women's health, particularly pronounced in developing countries. We aim to investigates the prevalence of self-reported RTI symptoms in women aged 18 to 65 and the factors influencing gynecological examination behavior and associated risks are explored. From May 6, 2022, to September 20, 2022, a comprehensive survey engaged 20,864 women aged 18 to 65 in 19 townships in Lueyang, Shaanxi. Each survey team, comprising a gynecologist, two female health center staff, and a master's student, conducted face-to-face questionnaire surveys in villages and households. The questionnaire featured three sections: prevalence of self-reported RTI symptoms, gynecological examination history, and factors influencing examination behavior. The high response rate of 98.69% yielded 20,590 valid questionnaires. Among surveyed women, 42.04% reported RTI symptoms, with a higher prevalence in those aged 30 and above, peaking at 44.88% in the 50-59 age group. Vulvar itching (24.73%), abnormal vaginal discharge (17.41%), and urinary tract irritation signs (11.73%) were most common. Older adult women (≥60) reported higher frequency and longer duration of symptoms. Only 9.88% of symptomatic women underwent gynecological examinations in 2022. Examination likelihood decreased with age, presenting a critical gap in healthcare utilization among older women. Reasons for checkups included routine checkups (47.02%), symptom concerns (41.29%), and the availability of free medical checkup programs (9.82%). Barriers included perceived lack of serious symptoms (23.7%), lack of necessity (4.41%) and lack of time (3.98%). Among those examined, 40.58% had a diagnosis of gynecological disorders, including pelvic inflammatory disease, human papilloma virus infection and cervical cancer. Widespread RTI symptoms, particularly in perimenopausal and older women, underscore the need for enhanced healthcare. Barriers to gynecological examinations include awareness, education, and accessibility issues. Strategies must prioritize health education, routine examinations, and improved healthcare infrastructure in underdeveloped regions.

Surface Morphology Analysis of Graphene Transfer on SiO2 with BPA Aptasensor Detection using Electrochemical Impedance Spectroscopy

Bisphenol A or BPA is one of the highest produced chemicals in the world. The production of polycarbonate plastic and epoxy resin are used to make variety of consumer goods and it is frequently employed BPA as a raw material. BPA is one of the endocrine disruptors which is related to a wide range of adverse health effects that can cause reproductive disorders and many kinds of cancers. In the work, the novelty of electrochemical sensor of BPA was constructed on a raphene modified electrode using graphene transfer method. In this work, High-power microscope and scanning electron microscopy were used to study the production and characterization of the graphene, with two significant mapping graphene at 20% and 80%. The existence of graphene on silicon oxide was analyzed using Raman Spectroscopy while the composition of the materials was analyze using Fourier-Transform Infrared Spectroscopy. In this analysis, both analysis data from Raman and FTIR clearly shown that 80% mapping graphene is the best option which resulting to the high surface coverage. The electrochemical performance of the mapping 80% graphene electrode was examined using Electrochemical Impedance Spectra. The increase in charge transfer resistance (Rct) both before and after the addition of BPA denotes the development of the charge at the electrode surface. The equivalent circuit shows the Rct of graphene increased from 0.4 k Ω to 1.2 k Ω and drastically increased to 300 kΩ when the device was introduced with BPA due to the existence of a negative charge carrier and the repelling contact.

Liver damage in galactosemia type I: a literary review

Galactosemia is a rare hereditary disease associated with impaired galactose metabolism, which is characterized by a wide range of clinical syndromes. Most long-term observations are devoted to the study of neurological, ophthalmological and reproductive disorders. Liver damage in galactosemia is one of the central manifestations of the disease, determining the severity and prognosis of the disease, mainly in the neonatal period. The lack of timely dietary correction in the neonatal period leads to severe liver damage with the development of cirrhosis, portal hypertension and liver failure. An information search has shown that prolonged and catamnestic studies on the condition of the liver in children with various variants of galactosemia, in particular, against the background of dietary correction, are few. Most studies show significant reversibility of hepatopathy on the background of diet (even with severe manifestation), however, the number of such publications is not large and the issue requires further research.