Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice.

BACKGROUND: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. METHODS: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. RESULTS: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. CONCLUSION: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.

Predicting nutrition and environmental factors associated with female reproductive disorders using a knowledge graph and random forests.

OBJECTIVE: Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (for example, endometriosis, ovarian cyst, and uterine fibroids). MATERIALS AND METHODS: We harmonized survey data from the Personalized Environment and Genes Study (PEGS) on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and applying a random forest for edge prediction to identify variables potentially associated with FRDs. We also conducted logistic regression analysis for comparison. RESULTS: Across 9765 PEGS respondents, the KG analysis resulted in 8535 significant or suggestive predicted links between FRDs and chemicals, phenotypes, and diseases. Amongst these links, 32 were exact matches when compared with the logistic regression results, including comorbidities, medications, foods, and occupational exposures. DISCUSSION: Mechanistic underpinnings of predicted links documented in the literature may support some of our findings. Our KG methods are useful for predicting possible associations in large, survey-based datasets with added information on directionality and magnitude of effect from logistic regression. These results should not be construed as causal but can support hypothesis generation. CONCLUSION: This investigation enabled the generation of hypotheses on a variety of potential links between FRDs and exposures. Future investigations should prospectively evaluate the variables hypothesized to impact FRDs.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study.

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28-1.59; P = 6.66 × 10-11), ovarian cysts (OR = 1.36, 95% CI 1.20-1.55; P = 1.57 × 10-6), AUB (OR = 1.41, 95% CI 1.20-1.66; P = 3.01 × 10-5), and endometriosis (OR = 1.43, 95% CI 1.27-1.70; P = 2.21 × 10-7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

Mapping the Landscape of Obesity Effects on Male Reproductive Function: A Bibliometric Study.

BACKGROUND: Due to changes in lifestyle and dietary habits, the global population with obesity is increasing gradually, resulting in a significant rise in the number of individuals having obesity. Obesity is caused by an imbalance between energy intake and consumption, leading to excessive fat accumulation, which interferes with normal human metabolism. It is also associated with cardiovascular disease, metabolic syndrome, male reproductive endocrine regulation disorders, systemic and local inflammatory reactions, excessive oxidative stress, and apoptosis. All these factors can damage the internal environment for sperm generation and maturation, resulting in male sexual dysfunction, a decline in sperm quality, and lower fertility. This study analyzes the trends and priorities of the effects of obesity on male reproductive disorders from a bibliometric perspective. METHODS: This study uses the Web of Science as the statistical source, covering all time spans. Tools like Web of Science, VOSviewer, and CiteSpace are used to analyze countries, institutions, authors, journals, and keywords in the field. Total publications, total citations, and average number of citations are selected for statistics. RESULTS: The results show that the research on the impact of obesity on male reproductive function can be roughly divided into three stages: the initial stage, the slow development stage, and the rapid development stage. Our statistical scope includes 463 highly relevant articles that we have screened. We found that the journal with the most publications in this field is Andrologia, and the institution with the highest total citations is the University of Utah. The most influential countries, institutions, and authors in this field are the United States, the University of Utah, and Carrell, Douglas. Currently, research related to the impact of obesity on male reproduction focuses mainly on three aspects: biochemistry, molecular biology, and reproductive biology. The keyword explosion results indicate that sperm, obesity, and male reproduction are at the forefront and trends of future research in this field. There has been a shift from basic biochemical and molecular research to research on molecular mechanisms relying on omics technologies. However, we have observed that the number of papers published in 2022 is lower than in 2021, indicating a growth interruption during this period. Considering that this deviation may be due to the impact of the COVID-19 pandemic, it may hinder the progress of certain experiments in 2022. In recent years, China has rapidly developed research in this field. However, the average citation rate is relatively low, indicating the need for Chinese scholars to improve the quality of their articles further. Based on our research and in the context of global obesity, men are at risk of increased infertility. Addressing this issue relies on our continued research into the mechanisms of obesity-related male reproductive disorders. Over the past forty-three years, with the contributions of scientists worldwide, research in this field has flourished. CONCLUSION: The impact of obesity on male reproductive disorders has been extensively studied. Currently, research in this field primarily focuses on male sperm function, sperm quality, and the effects or mechanisms of cells on male reproduction. Future trends in this field should concentrate on the relationship between male fertility and energy metabolism, as well as the endocrine function of adipose tissue. This study comprehensively analyzes the current research status and global trends in obesity and male reproductive disorders. We also discuss the future developments in this field, making it easier for researchers to understand its developmental history, current status, and trends, providing valuable reference for effective exploration in this area.

Impact of DEHP exposure on female reproductive health: Insights into uterine effects.

Several endocrine disrupting compounds released from plastics, including polyfluoroalkyl substances, bisphenols, flame retardants, phthalates and others, are of great concern to human health due to their high toxicity. This review discusses the effects of di-(2-ethylhexyl) phthalate (DEHP), the most common member of the phthalate family, on female reproduction. In vitro and in vivo studies link DEHP exposure to impaired hypothalamic-pituitary-ovarian s (HPO) axis function, alteration of steroid-hormone levels and dysregulation of their receptors, and changes in uterine morphophysiology. In addition, high urinary DEPH levels have been associated with several reproductive disorders in women, including endometriosis, fibromyoma, fetal growth restriction and pregnancy loss. These data suggest that DEHP may be involved in the pathophysiology of various female reproductive diseases. Therefore, exposure to these compounds should be considered a concern in clinician surveillance practices for women at reproductive age and should be regulated to protect their health and that of their progeny.

Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies.

Rheumatoid arthritis (RA) is a common inflammatory arthritis in women. The effects of RA on the reproductive system are usually overlooked, as RA is not diagnosed until later in reproductive age. Whether RA itself or its related rheumatoid antibodies have an impact on female reproductive function has long been a thought-provoking issue. In brief, relevant epidemiological evidence has shown that women affected by RA are more likely to have coexisting reproductive disorders, including infertility, endometriosis, and premature ovarian insufficiency (POI), or to subsequently develop them. Furthermore, linkage between RA and pregnancy loss (PL) as well as polycystic ovary syndrome (PCOS) is also well known, albeit controversial in available evidence. RA and reproductive disorders appear to share a similar inflammatory immune response and genetic background. The stress experienced by patients with RA may affect their reproductive choices to some extent. Notably, few studies have explored the impact of rheumatoid antibodies such as rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs) on reproductive disorders. Although it has been mentioned that the rate of RF and/or ACPA positivity is higher in women with a history of PL and POI, the clinical relevance of this relationship and underlying mechanisms still need to be further clarified.

Recent Advances in Nanotechnology-Based Drug Delivery Systems for the Diagnosis and Treatment of Reproductive Disorders.

Over the past decade, nanotechnology has seen extensive integration into biomedical applications, playing a crucial role in biodetection, drug delivery, and diagnostic imaging. This is especially important in reproductive health care, which has become an emerging and significant area of research. Global concerns have intensified around disorders such as infertility, endometriosis, ectopic pregnancy, erectile dysfunction, benign prostate hyperplasia, sexually transmitted infections, and reproductive cancers. Nanotechnology presents promising solutions to address these concerns by introducing innovative tools and techniques, facilitating early detection, targeted drug delivery, and improved imaging capabilities. Through the utilization of nanoscale materials and devices, researchers can craft treatments that are not only more precise but also more effective, significantly enhancing outcomes in reproductive healthcare. Looking forward, the future of nanotechnology in reproductive medicine holds immense potential for reshaping diagnostics, personalized therapies, and fertility preservation. The utilization of nanotechnology-driven drug delivery systems is anticipated to elevate treatment effectiveness, minimize side effects, and offer patients therapies that are not only more precise but also more efficient. This review aims to delve into the various types, properties, and preparation techniques of nanocarriers specifically designed for drug delivery in the context of reproductive disorders, shedding light on the current landscape and potential future directions in this dynamic field.

Seroprevalence of Coxiella burnetii, Leptospira interrogans serovar hardjo, and Brucella species and associated reproductive disorders in cattle in southwest Ethiopia.

In Ethiopia, Coxiella burnetii, Leptospira Hardjo, and Brucella spp are recognized as the primary factors contributing to cattle reproductive issues. A cross-sectional study was conducted in southwest Ethiopia from October 2020 to October 2021 to assess the risk of reproductive disorders associated with L. Hardjo, Coxiella burnetii, and Brucella spp. Moreover, the study aimed to identify the factors associated with reproductive disorders. Using an indirect ELISA, antibodies against these pathogens were observed in serum samples collected from 461 cattle. We employed multivariable random effect logistic regression analysis to identify potential risk factors associated with reproductive disorders in cattle. The study areas showed a prevalence of 25.16 % (95 % CI: 21.20-29.12) for cattle reproductive disorders. The presence of Leptospira Hardjo (OR = 2.9, 95 % CI: 1.17-4.02) and Coxiella burnetii (OR = 3.0, 1.49-5.94) antibodies was associated to the occurrence of cattle reproductive disorders. Seropositivity to pathogens B. abortus, C. burnetii, and L. Hardjo, along with co-infection of all three, showed association with cattle abortion. The presence of L. Hardjo seropositivity and co-infection with C. burnetii were related to dystocia in cattle. Cattle with retained fetal membranes were associated with co-infection seropositivity to these pathogens. Additionally, B. abortus seropositivity was linked to cases of repeated breeding in cattle. Age, breeding practices, and dog access to cattle showed associations with reproductive disorders, with odds ratios of 2.3 (95 % CI: 2.03-4.69), 2.9 (95 % CI: 1.83-4.82), and 6.5 (95 % CI: 1.04-2.53) respectively. This research indicates that Brucella abortus, Coxiella burnetii, and Leptospira Hardjo, which are responsible for severe zoonotic diseases, have a substantial negative impact on cattle production by causing reproductive disorders. To address the transmission of these diseases, it is essential to implement effective mitigation strategies and enhance public awareness. Additional investigation is necessary to identify and understand the factors contributing to cattle reproductive disorders in the specified area.

Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.

In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success.

NLRP2 in health and disease.

NLR family pyrin domain containing 2 (NLRP2) is a novel member of the Nod-like receptor (NLR) family. However, our understanding of NLRP2 has long been ambiguous. NLRP2 may have a role in the innate immune response, but its 'specific' functions remain controversial. Although NLRP2 can initiate inflammasome and promote inflammation, it can also downregulate inflammatory signals. Additionally, NLRP2 has been reported to function in the reproductive system and shows high expression in the placenta. However, the exact role of NLRP2 in the reproductive system is unclear. Here, we highlight the most current progress on NLRP2 in inflammasome activation, effector function and regulation of nuclear factor-κB. And we discuss functions of NLRP2 in inflammatory diseases, reproductive disorders and the potential implication of NLRP2 in human diseases.

Association between Late Manifestations of Testicular Dysgenesis Syndrome and Anogenital Distance: A Systematic Review and Meta-analysis.

Background: In 2001, Skakkebæk et al. proposed that certain male reproductive disorders might be grouped into a syndrome called testicular dysgenesis syndrome (TDS), as they all appear to be associated with disruption of the embryonic and foetal programming of gonadal development. TDS may be manifested in early life by the presence of genital malformations (hypospadias and cryptorchidism) and in adult life as disorders represented by low sperm counts and testicular cancer. Changes in androgen hormones during the foetal development, in addition to resulting in TDS, can also cause permanent changes in anopenile anogenital distance (AGDap) and anoscrotal anogenital distance (AGDas). Aims: The objective of this study was to determine whether there is a relationship between late manifestations of TDS and reduced anogenital/anoscrotal distance. Materials and Methods: The present study is a systematic review and meta-analysis. The research included papers from 2001 to 2020, comprising a total of 737 articles, and 13 articles were selected. Results: Linear regression analysis was performed to evaluate the relationship between the two anogenital distance measures, which showed a significant positive association (P = 0.039). A meta-analysis was also performed and compared AGDap and AGDas between control and case groups, with cases defined as men with any late TDS manifestation. These data showed a significant reduction in AGDas in the affected population (P = 0.04), but no differences in the AGDap measure (P = 0.59). Conclusion: Our study confirmed a significant relationship between reduced AGDas and late manifestations of TDS, providing further support to the association between prenatal androgen deficiency and late-onset reproductive disorders.

Identification of Genomic Instability in Cows Infected with BVD Virus.

An important factor for dairy cattle farmers is the profitability of cattle rearing, which is influenced by the animals' health and reproductive parameters, as well as their genomic stability and integrity. Bovine viral diarrhea (BVD) negatively affects the health of dairy cattle and causes reproductive problems. The aim of the study was to identify genomic instability in cows with reproductive disorders following infection with the BVD virus. The material for analysis was peripheral blood from Holstein-Friesian cows with reproductive problems, which had tested positive for BVD, and from healthy cows with no reproductive problems, which had tested negative for BVD. Three cytogenetic tests were used: the sister chromatid exchange assay, fragile sites assay, and comet assay. Statistically significant differences were noted between the groups and between the individual cows in the average frequency of damage. The assays were good biomarkers of genomic stability and enabled the identification of individuals with an increased frequency of damage to genetic material that posed a negative impact on their health. The assays can be used to prevent disease during its course and evaluate the genetic resistance of animals. This is especially important for the breeder, both for economic and breeding reasons. Of the three assays, the comet assay proved to be the most sensitive for identifying DNA damage in the animals.

Cellular inflammatory response in the bovine uterus by Leptospira infection may be related to embryo death and subfertility.

Bovine leptospirosis is a chronic disease that causes various reproductive disorders and consequent economic losses worldwide, particularly embryo death. Although Leptospira spp. has already been detected in the genital tract of cows, little is known about the uterine cellular immune response or the intrinsic factors that could contribute to that reproductive failure. In this context, the aim of this study was to assess the uterine cellular inflammatory response after the quantification of cytokine IL-6 in bovine uteri naturally infected with leptospires compared to uninfected. Our results demonstrated that uterine tissues infected with leptospires have higher levels of IL-6 compared to uninfected tissues (p < 0.001). It suggests that the presence of leptospires in the bovine uterus can induce a cellular inflammatory response, which may be related to embryo death and consequent subfertility.

The role of the thyroid in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.

The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS.

Introduction: Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes. Methods: This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia. Results: The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes. Conclusion: Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.

DNA Polymorphisms and mRNA Levels of Immune Biomarkers as Candidates for Inflammatory Postpartum Disorders Susceptibility in Italian Buffaloes.

The immunological genes that may interact with inflammatory postpartum diseases in Italian buffaloes were examined in this study. A total number of 120 female Italian buffaloes (60 normal and 60 with inflammatory reproductive diseases) were employed. Each buffalo's jugular vein was pierced to get five milliliters of blood. To obtain whole blood and extract DNA and RNA, the blood was placed within tubes containing sodium fluoride or EDTA anticoagulants. The immunological (IKBKG, LGALS, IL1B, CCL2, RANTES, MASP2, HMGB1, and S-LZ) genes' nucleotide sequence differences between healthy buffaloes and buffaloes affected by inflammatory reproductive diseases were found by employing PCR-DNA sequencing. According to Fisher's exact test (p ˂ 0.01), there were noticeably different probabilities of all major nucleotide changes spreading among buffalo groups with and without reproductive problems. Buffaloes were significantly more likely to express the examined genes when they had inflammatory reproductive diseases. The outcomes might support the significance of these markers' nucleotide variations and gene expression patterns as indicators of the prevalence of inflammatory reproductive disorders and provide a workable buffalo management policy.

The emerging role of ferroptosis in female reproductive disorders.

Iron, as an essential trace element for the organism, is vital for maintaining the organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis is a novel form of programmed cell death distinguished by iron overload and lipid peroxidation, which is unique from autophagy, apoptosis and necrosis, more and more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis is associated with the development of female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), ovarian cancer (OC), preeclampsia (PE) and spontaneous abortion (SA). Pathways and genes associated with ferroptosis may participate in processes that regulate granulosa cell proliferation and secretion, oocyte development, ovarian reserve function, early embryonic development and placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates the occurrence mechanism of ferroptosis and its research progress in the development of FRDs, with a view to providing literature references for clinical targeting of ferroptosis -related pathways and regulatory factors for the management of FRDs.

Engineered extracellular vesicles in female reproductive disorders.

Biologically active and nanoscale extracellular vesicles (EVs) participate in a variety of cellular physiological and pathological processes in a cell-free manner. Unlike cells, EVs not only do not cause acute immune rejection, but are much smaller and have a low risk of tumorigenicity or embolization. Because of their unique advantages, EVs show promise in applications in the diagnosis and treatment of reproductive disorders. As research broadens, engineering strategies for EVs have been developed, and engineering strategies for EVs have substantially improved their application potential while circumventing the defects of natural EVs, driving EVs toward clinical applications. In this paper, we will review the engineering strategies of EVs, as well as their regulatory effects and mechanisms on reproductive disorders (including premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), recurrent spontaneous abortion (RSA), intrauterine adhesion (IUA), and endometriosis (EMS)) and their application prospects. This work provides new ideas for the treatment of female reproductive disorders by engineering EVs.