Reproductive System Disorders Research Articles

Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.

Infertility is a multifactorial reproductive system disorder,and most infertility cases occur inmen. Semen testing is now thought to be the most important diagnostic test for infertile men; nonetheless, because of its limitations, the cause of infertility remains unknown for 40% of infertile men. Semen assessment's shortcomings indicate the need for improved and innovative diagnostic techniques and biomarkers worldwide. Non-coding RNAs with a length of roughly 18-22 nucleotides are called microRNAs (miRNAs). Most of our protein-coding genes are post-transcriptionally regulated by them. These molecules are unusual in bodily fluids, and aberrant variations in their expression can point to specific conditions like infertility. As a result, fresh potential biomarkers for the diagnosis and prognosis of various forms of male infertility may be represented by miRNAs. This reviewexamined the most recent research revealing the association between different miRNAs' functions in male infertility and their expression patterns. Also, it aims to figure out the most recent strategies that could be applied for using such miRNAs as possible therapeutic targets for infertility treatment.

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.

Safety study on adverse events of zanubrutinib based on WHO-VigiAccess and FAERS databases.

The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions. We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis. The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc. This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Social Media as a Source of Information for the Detection of Adverse Drug Reactions in Post-Marketing Surveillance: A Review

INTRODUCTION. With the development of the Internet and the increasing availability of social networks and fora, patients have received an opportunity to share their medication experiences online. According to the guidelines on Good Pharmacovigilance Practices, social media can be considered an important additional source of patient-derived information in post-marketing surveillance, but the effectiveness of their use in detecting adverse drug reactions (ADRs) is still being investigated.AIM. This study aimed to analyse the results of relevant original studies and assess the potential of using social networks and online patient fora as a source of information on ADRs associated with the use of medicinal products.DISCUSSION. Published studies indicate that posts on social networks and patient fora describe both minor and serious ADRs, including new ADRs. The relevance of social media as a source of information about the safety of a medicinal product varies depending on several factors, including the medicinal product class and time on the market, as well as the platform demographics. Young users (18–44 years) are interested in online discussions about medicinal products for mental and reproductive system disorders. Users aged 45–64 years tend to discuss the use of medicinal products for chronic pain (including muscle pain), menopause, and gastritis. Discussions among users over 65 years old predominantly focus on medicinal products for diabetes, heart conditions, and muscle pain. People are much more likely to describe ADRs associated with the use of medicinal products for orphan diseases and cancer on fora for patients than on social networks in general, and vice versa for ADRs associated with the use of medicinal products for mental disorders. In addition, social media may be of interest as a source of information about cases of overdose, misuse and off-label use of medicinal products, and use of medicinal products during pregnancy and lactation.CONCLUSIONS. Social media can be a source of valuable information about the safety of medicinal products and the impact of ADRs on the quality of patients’ lives. Marketing authorisation holders can obtain new information about the safety of medicinal products by extending their safety monitoring strategies to include social media. Nevertheless, since the relevance of a particular social network or patient forum for the detection of ADR cases varies considerably, a preliminary assessment is necessary to ascertain the presence of information on the medicinal product of interest.

A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for reproductive disorders including primary ovarian insufficiency, polycystic ovary syndrome, and abnormal spermatozoa

BackgroundAccumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (GDMs) and reproductive diseases, including primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and abnormal spermatozoa (AS), still await thorough clarification.MethodsWith the currently most comprehensive genome-wide association studies (GWAS) data of metabolomics, systematic two-sample Mendelian randomization (MR) analyses were conducted to disclose causal associations between 1,091 blood metabolites and 309 metabolite ratios with reproductive disorders. The inverse-variance weighted (IVW) method served as the primary analysis approach, and multiple effective MR methods were employed as complementary analyses including MR-Egger, weighted median, constrained maximum likelihood (cML-MA), contamination mixture method, robust adjusted profile score (MR-RAPS), and debiased inverse-variance weighted method. Heterogeneity and pleiotropy were assessed via MR-Egger intercept and Cochran’s Q statistical analysis. Outliers were detected by Radial MR and MR-PRESSO methods. External replication and metabolic pathway analysis were also conducted.ResultsPotential causal associations of 63 GDMs with POI were unearthed, and five metabolites with strong causal links to POI were emphasized. Two metabolic pathways related to the pathogenesis of POI were pinpointed. Suggestive causal effects of 70 GDMs on PCOS were detected, among which 7 metabolites stood out for strong causality with elevated PCOS risk. Four metabolic pathways associated with PCOS mechanisms were recognized. For AS, 64 GDMs as potential predictive biomarkers were identified, particularly highlighting two metabolites for their strong causal connections with AS. Three pathways underneath the AS mechanism were identified. Multiple assessments were conducted to further confirm the reliability and robustness of our causal inferences.ConclusionBy extensively assessing the causal implications of circulating GDMs on reproductive system disorders, our study underscores the intricate and pivotal role of metabolomics in reproductive ill-health, laying a theoretical foundation for clinical strategies from metabolic insights.

Feasibility of submaterial module for reproductive system disorders based on inventory of medical plants

Modules are teaching materials designed to be studied by students independently or with minimal guidance from educators because they are equipped with their learning instructions. This study aims to determine the feasibility of teaching materials for reproductive system disorders submaterial modules from the inventory of medicinal plants that facilitate and relieve menstrual pain in Tumiang Village, Samalantan District, Bengkayang Regency. The research method was used research and development (R&D) Borg and Gall model, including potential problems, data collection, product design, design validation, and product revision. The validation of the teaching materials was done by five validators using validation sheets. The aspects assessed in the validation sheet consist of content, language, presentation, and graphics. The validation data were analyzed using the Content Validity Ratio (CVR) and the Content Validity Index (CVI). The results of the validation of the module’s instructional materials yielded a CVR value of 1.00 for each criterion with a valid category and a CVI value of 1.00 with a valid category. Based on these results, it can be concluded that the module on reproductive system disorders from the results of the inventory of medicinal plants that facilitate and relieve menstrual pain is suitable for use as teaching material.

Developing glycoproteomics reveals the role of posttranslational glycosylation in the physiological and pathological processes of male reproduction

AbstractGlycosylation plays a pivotal role in the physiological and pathological processes of male reproduction. It impacts thousands of proteins and is actively ongoing through all stages of reproduction, including spermatogenesis, maturation, capacitation, and fertilization. However, our grasp on glycosylation within male reproductive processes remains limited, largely due to the technical hurdles. Recent advancements have seen the mapping of the glycoproteome of human semen, utilizing cutting‐edge glycoproteomic technologies. This breakthrough lays the groundwork for in‐depth research into the influence of glycosylation on male reproductive system and related disorders. Nevertheless, the field faces numerous challenges that necessitate further advancements in glycoproteomic methodologies. In this analysis, we evaluated the potential applications of advanced glycoproteomic techniques in the study of male reproduction and summarized the detailed profiling of the human semen glycome and glycoproteome. Our current understanding of glycosylation's role within the male reproductive system alongside recent progress in glycoproteomics may equip biologists with a comprehensive insight. Furthermore, this analysis brought together findings on abnormal glycosylation and its link to male reproductive disorders in the view of glycomics and glycoproteomics. It can facilitate the clinical application of glyco‐related biomarkers and targets in the treatment of infertility.

Post-marketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.

Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

Immune checkpoint inhibitor-related reproductive adverse effects: A pharmacovigilance analysis based on the FAERS database.

e14707 Background: There exists a critical need to systematically understand the extent and magnitude of immune checkpoint inhibitor (ICI)-related reproductive adverse effects, which may not only pose long-term implications for patients who may desire future fertility, but also impact the quality of life. We aim to better understand this underexplored area. Methods: Our focus was on ICIs approved by the FDA as of June 31, 2023, including anti-PD-1 agents (nivolumab, pembrolizumab, cemiplimab, dostarlimab, retifanlimab), anti-PD-L1 agents (atezolizumab, avelumab, durvalumab), anti-CTLA-4 agents (ipilimumab, tremelimumab), and an anti-LAG-3 agent (relatlimab). We analyzed 13,702,373 cases from January 1, 2015, to June 30, 2023. We included adverse reactions under the 'Reproductive system and breast disorders' category in the SOC (System Organ Classes). For signal detection, we used the reporting odds ratio (ROR) method. Results: We identified 133,512 patients administered with ICIs, among whom 568 reported irRAEs. Abnormal spermatogenesis (ROR025: 7.91), scrotal irritation (ROR025: 3.83), scrotal oedema (ROR025: 1.90), perineal rash (ROR025: 1.38), prostatitis (ROR025: 1.25), acquired phimosis (ROR025: 1.20), and scrotal erythema (ROR025: 1.08) in males and genital tract fistula in females (ROR025: 2.72) were detected as significant irRAEs. Among them, the most commonly reported irRAEs were prostatitis (n=29), scrotal oedema (n=12), and abnormal spermatogenesis (n=6) in males and genital tract fistula (n=34) in females. Male patients had a lower risk compared to females (OR=0.68 [0.57-0.81], p<0.0001). There was no marked difference between the patients on polytherapy vs. monotherapy (OR=0.90 [0.71-1.13], p=0.36). PD-1 inhibitors pose the greatest risk when compared with CTLA-4 inhibitors (OR=1.65 [1.05-2.79], p=0.045). Gynecologic cancers in females (OR=3.77 [2.82-4.99], p<0.0001) and urogenital cancers in males (OR=1.56 [1.17-2.06], p=0.0018) were strong risk factors. Additional targeted therapy, particularly lenvatinib (OR=3.79 [2.71-5.15], p<0.0001) and cabozantinib (OR=2.69 [1.66-4.09], p<0.0001) significantly increased the risk (OR=1.87 [1.52-2.29], p<0.0001) and this risk appeared to be more pronounced in females (OR=2.32 [1.76-3.02], p<0.0001). Additional chemotherapy was associated with a significantly reduced risk in males (OR=0.65 [0.42-0.96], p=0.042). However, doxorubicin (OR=2.58 [1.10-5.05], p=0.013) and cyclophosphamide (OR=2.36 [0.93-4.83], p=0.038) were linked to an elevated risk. Conclusions: Our findings demonstrated that ICIs could lead to a wide range of irRAEs in both males and females. Additional therapies could change the risk of irRAEs. Despite the current lack of high-quality clinical data on this topic, it is reasonable to inform patients about the plausible risk of irRAEs.

Safety assessment of clomiphene: a real-world pharmacovigilance analysis from the Food and Drug Administration adverse event reporting system

ABSTRACT Background Clomiphene is widely used for the treatment of anovulatory infertility, yet there remain many unrecognized adverse events (AEs). The objective of this study is to provide a comprehensive overview of the safety profile of clomiphene. Methods The data were derived from the first quarter of 2004 to the third quarter of 2023 from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The detection of new AE signals involved the use of four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). Results A total of 16,677,289 AE reports were acquired from the FAERS database, and there were 2,620 AEs specifically reported in 720 patients following clomiphene use. The AEs encompassed 102 preferred terms (PTs) across 24 system organ classes (SOCs). Some new AEs were identified, including conjoined twins (0.5%), Potter’s syndrome (0.3%), genitalia external ambiguous (0.3%), esophageal atresia (0.6%), and anal atresia (0.3%). Conclusions Although the majority of AEs aligned with the drug instruction, some new AE signals such as conjoined twins and genitalia external ambiguous were not captured. Well-designed studies are required to demonstrate the safety of clomiphene.

Potential adverse events associated with sphingosine-1-phosphate (S1P) receptor modulators in patients with multiple sclerosis: an analysis of the FDA adverse event reporting system (FAERS) database

ObjectiveSphingosine-1-phosphate receptor (S1PR) modulators have recently attracted increasing attention for the treatment of multiple sclerosis (MS). Despite their preference in the clinic, multiple adverse events (AEs) continue to be reported every year. This study aimed to investigate the potential AEs as well as related important medical events (IMEs) signal associated with S1PR modulators, including fingolimod, siponimod and ozanimod in a real-world study using the FDA Adverse Event Reporting System (FAERS) database.MethodsAll data were collected from the FAERS database, spanning from the fourth quarter of 2010(2010Q4) to the second quarter of 2023 (2023Q2). Potential AE and IME signals of S1PR modulators were identified based on a disproportionality analysis using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and the bayesian confidence propagation neural network of information components (IC).ResultsOverall, 276,436 reports of fingolimod, 20,972 reports of siponimod and 10,742 reports of ozanimod were analyzed from the FAERS database. Among reports, females were more prone to develop AEs (73.71% for females vs. 23.21% for males), and more than 50% of patients suffered from AEs were between 18 and 64 years. Subsequently, we investigated the top 20 AEs associated with the signal strength of S1PR modulators at the preferred term (PT) level, and identified 31 (8 vs. 11 vs. 12, respectively) unlabeled risk signals such as thrombosis, uterine disorder and reproductive system and breast disorders. Furthermore, we discovered that the S1PR modulator reported variations in the possible IMEs, and that the IMEs associated with ocular events were reported frequently. It’s interesting to note that infection and malignancy are prominent signals with both fingolimod and siponimod in the top 20 PTs related to mortality reports.ConclusionThe present investigation highlights the possible safety risks associated with S1PR modulators. The majority of AEs are generally consistent with previous studies and are mentioned in the prescribing instructions, however, several unexpected AE signals have also been observed. Ozanimod showed the lowest signal intensity and a better safety profile than the other S1PR modulators. Due to the short marketing time of drugs and the limitations of spontaneous reporting database, further research is required to identify potential AEs related to S1PR modulators.

Therapeutic Potential of Hydrogen Sulfide in Reproductive System Disorders.

Hydrogen sulfide (H2S), previously regarded as a toxic exhaust and atmospheric pollutant, has emerged as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO). Recent research has revealed significant biological effects of H2S in a variety of systems, such as the nervous, cardiovascular, and digestive systems. Additionally, H2S has been found to impact reproductive system function and may have therapeutic implications for reproductive disorders. This paper explores the relationship between H2S and male reproductive disorders, specifically erectile dysfunction, prostate cancer, male infertility, and testicular damage. Additionally, it examines the impact of H2S regulation on the pathophysiology of the female reproductive system, including improvements in preterm birth, endometriosis, pre-eclampsia, fetal growth restriction, unexplained recurrent spontaneous abortion, placental oxidative damage, embryo implantation, recovery of myometrium post-delivery, and ovulation. The study delves into the regulatory functions of H2S within the reproductive systems of both genders, including its impact on the NO/cGMP pathway, the activation of K+ channels, and the relaxation mechanism of the spongy smooth muscle through the ROCK pathway, aiming to broaden the scope of potential therapeutic strategies for treating reproductive system disorders in clinical settings.

Serological Investigation of Bovine Enterovirus in Calves in Konya Province

Bovine enterovirus (BEV) infection is a common viral disease in cattle. Although the infection is often subclinical, it is among the possible causes of gastroenteritis. BEV infections have also been associated with respiratory and reproductive system disorders and signs of diarrhea. BEV is divided into two serotypes, enterovirus serotype E (EV-E) and enterovirus serotype F (EV-F). This study aims to determine the seroprevalence of EV-E in calves in Konya province. For this purpose, 504 BEV unvaccinated calf blood serum samples from the Selcuk University Veterinary Faculty Virology Department laboratory were used. A serum neutralization test (SNT) was used to determine EV-E seroprevalence. 342 (67.85%) samples were found to be seropositive, and 162 (32.14%) were seronegative. In addition, as the serum neutralization 50 (SN50) antibody titers of seropositive animals were examined, the titers determined as 1/10, 1/15 and 1/20. Among the results we obtained, the highest antibody titers were defined as 1/80 and 1/120; the total number of animals with these values was In conclusion, bovine enteroviruses are an infection of importance for cattle breeding. Therefore, necessary precautions must be taken to protection infection. It is thought that the results of the present study will provide important data for future studies.

Вплив артифіційних абортів на стан репродуктивного здоров’я жінок фертильного віку. Результати когортного дослідження

Data on the negative impact of artificial abortions in the early stages on a woman's reproductive health are contradictory. Variables that may affect the results include study design, gestational age at the time of abortion, duration of follow-up, and procedure’s type. Aim - to analyze the impact of early artificial abortions on the reproductive womenʼs health. Materials and methods. A retrospective cohort study was conducted, which included 549 consecutively recruited women, of which: 119 respondents with a history of induced abortions made up the experimental group, 430 without artificial termination of pregnancy - the comparison group. An analysis of the gynecological and obstetrical anamnesis was carried out. Statistical data processing was carried out using the SPSS 21 program. Results. It was established that the presence of artificial abortions in the anamnesis is associated with an increase in the frequency of infertility, colpitis, cervix dysplasia, salpingo-oophoritis, uterus inflammatory diseases, habitual miscarriage, and also increase in the obstetric complications frequency (spontaneous miscarriages at an early stage, the threat of termination of pregnancy, premature births, abdominal surgical delivery, placental complications). Conclusions. Analysis of the artificial abortions consequences indicates the presence of various disorders in reproductive system of fertile women. This study did not involve any experiments on animals or humans. No conflict of interests was declared by the authors.

Hubungan Antara Kadar Hormon Dengan Perdarahan Di Luar Siklus Menstruasi Pada Wanita Usia Subur

Bleeding disorders outside the menstrual cycle are reproductive system disorders commonly experienced by women during their reproductive years. These disorders are characterized by changes in menstrual periods, including alterations in cycle length, duration of menstruation, or volume of bleeding, with a worldwide prevalence ranging from 3% to 30%. Hormonal factors are often implicated as causes of bleeding disorders outside the menstrual cycle. Preliminary findings from a study conducted at RSIA Puri revealed that three female patients seeking treatment experienced bleeding disorders outside the menstrual cycle, with two of them exhibiting low estrogen levels (below 20 pg/ml) upon examination. The purpose of this study was to analyze the relationship between hormone levels, particularly estrogen, and bleeding outside the menstrual cycle in women of childbearing age at RSIA Puri Malang. The research employed a quantitative analysis through a cross-sectional approach. Primary and secondary data were obtained from laboratory examinations of estrogen levels in blood serum on the third day of menstruation. The sample consisted of 34 mothers who met the criteria of experiencing menstrual disorders and visited RSIA Puri Malang, and who willingly participated as respondents, selected through quota sampling. Data analysis was conducted using the Chi-square test, and the results revealed a significant relationship between estrogen levels and bleeding outside the menstrual cycle, or metrorrhagia (p-value = 0.018; OR = 0.107). This suggests that estrogen hormone regulation plays a crucial role in preventing menstrual irregularities. In conclusion, maintaining optimal estrogen hormone levels is essential for preventing and managing menstrual irregularities and bleeding disorders outside the menstrual cycle.

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women.

Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system's normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs-Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)-to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

A real-world disproportionality analysis of Everolimus: data mining of the public version of FDA adverse event reporting system.

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results. Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label. Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus.

Caffeine attenuates spermatogenic disorders in mice with induced chronic scrotal hyperthermia.

Chronic scrotal hyperthermia (SHT) can lead to serious disorders of the male reproductive system, with oxidative stress playing a key role in the onset of these dysfunctions. Thus, we evaluated the impact of caffeine, a potent antioxidant, on cellular and tissue disorders in mice with chronic SHT. In this experimental study, 56 adult male NMRI mice were allocated into seven equal groups. Apart from the non-treated control group, all were exposed to heat stress. Two groups, termed "preventive" and "curative," were orally administered caffeine. The preventive mice began receiving caffeine immediately prior to heat exposure, while for the curative group, a caffeine regimen was initiated 15 consecutive days following cessation of heat exposure. Each treated group was subdivided based on pairing with a positive control (Pre/curative [Cur]+PC) or a vehicle (Pre/Cur+vehicle). Upon conclusion of the study, we assessed sperm characteristics, testosterone levels, stereological parameters, apoptosis, antioxidant and oxidant levels, and molecular markers. Sperm parameters, testosterone levels, stereological parameters, biochemical factors (excluding malondialdehyde [MDA]), and c-kit gene expression were significantly elevated in the preventive and curative groups, especially the former, relative to the other groups. Conversely, expression levels of the heat shock protein 72 (HSP72) and nuclear factor kappa beta (NF-κβ) genes, MDA levels, and apoptotic cell density were markedly lower in both caffeine-treated groups relative to the other groups, with more pronounced differences observed in the preventive group. Overall, caffeine attenuated cellular and molecular abnormalities induced by heat stress in the testis, particularly in the mice treated under the preventive condition.

The Potential of Tissue Engineering in Treatment of Female Reproductive System Disorders: A Review

The Potential of Tissue Engineering in Treatment of Female Reproductive System Disorders: A Review

Magnetic resonance imaging in the diagnosis of functional changes of the brain in menstrual disorders: a review

INTRODUCTION: Currently, the most common variant of the reproductive system disorders, in particular menstrual cycle disorders, in adolescent girls is oligomenorrhea. In situations after a complete diagnostic screening no organic and endocrine pathology of the reproductive system is detected in this group of patients, it is possible to conduct functional MRI as a method of identifying cause-and-effect relationships and clarifying the pathogenesis of menstrual disorders.OBJECTIVE: To analyze the available foreign and domestic literature to determine the role of magnetic resonance imaging in the diagnosis of functional brain changes in menstrual disorders in adolescent girls.MATERIALS AND METHODS: A search was conducted for scientific publications in the information and analytical systems PubMed and Google Scholar for 2013–2023 by keywords: «resting-state functional MRI» («functional resting MRI»), «oligomenorrhhea» («oligomenorrhea»), «adolescent girls» («teenage girls»), «reproductive system functional disorders» («functional disorders of the reproductive system»), «magnetic resonance imaging» («magnetic resonance imaging»), «diagnostic radiology» («radiation diagnostics»). 46 publications related to the diagnosis of functional brain changes in menstrual disorders in the form of resting state fMRI were analyzed.RESULTS: Resting state fMRI allows us to assess the basic brain activity in the absence of certain sensory or cognitive stimuli and visualize working networks that include various parts of the brain demonstrating synchronous changes in the BOLD-signal at rest. There are a number of patterns of changes in the BOLD-signal that can be observed in various phases of the menstrual cycle, as well as under the influence of stress factors, which makes it possible to visualize the morphological substrate of oligomenorrhea that occurs against the background of the absence of organic and endocrine pathology of the reproductive system in adolescent girls. Currently, there is little data in the scientific literature on the use of functional resting MRI in this cohort of patients, however, this method can have a significant impact on the formation of an individual plan for the correction of reproductive disorders in adolescence, and therefore requires further study.CONCLUSION: The use of fMRI can open up new possibilities in the diagnosis of functional brain disorders in girls with «unexplained» oligomenorrhea.