Reproductive Sciences最新文献

{"title":"Targeting Decidual Macrophage Polarization through JNK Signaling Pathway Inhibition Alleviates Adverse Pregnancy Outcomes in Early Spontaneous Abortion.","authors":"Zhao-Jin Luan, Yi Yang, Shi-Wei Liang, Yao Ma, Yong-Hong Li, Zi-Wei Zhao, Xiao-Ling Gong, Mei-Xia Yang, Fang Song","doi":"10.1007/s43032-025-01915-6","DOIUrl":"https://doi.org/10.1007/s43032-025-01915-6","url":null,"abstract":"<p><p>Early spontaneous abortion (ESA) is associated with abnormal decidual macrophage polarization at the maternal-fetal interface. While JNK signaling is recognized in implantation and immunomodulation, its contribution to decidual macrophage polarization in the ESA is poorly understood. The decidual tissues of ESA patients were collected to detect the polarization status and the expression of JNK1/2 and p-JNK in decidual macrophages (DMs) through flow cytometry assessment. PMA-induced THP-1 cell differentiation into macrophage phenotypes in vitro. To enhance our knowledge of macrophage polarization, activation of M1 macrophages was achieved using LPS and IFN-γ, while activation of M2 macrophages was accomplished using IL-4 and IL-13, followed by treatment with varying concentrations of the JNK inhibitor (SP600125) to see how it affected the balance between the two macrophage types. The impact of the JNK signaling pathway on macrophage polarization and pregnancy outcomes in spontaneous abortion mouse models was assessed. Our findings revealed enhanced M1 polarization and dysregulated JNK phosphorylation in decidual macrophages from ESA patients. Inhibition of the JNK by SP600125 shifted macrophage differentiation toward the M2 phenotype, enhancing production of TGF-β and IL-10. Concurrently, it inhibited M1 macrophage polarization, lessening inflammatory mediator secretion, notably TNF-α and IL-6. Furthermore, blocking the JNK signaling pathway significantly increased the M2 phenotype of DMs and reduced the resorption rate of mouse embryos. The current study elucidated that blocking the JNK signaling pathway suppressed the pro-inflammatory polarization in macrophages, thereby attenuating the adverse pregnancy outcomes of ESA.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Composite Dietary Antioxidant Index and Pregnancy: Insights from the NHANES.","authors":"Yi-Fan Kang, Jian-Rong Liu","doi":"10.1007/s43032-025-01905-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01905-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;A substantial body of empirical evidence suggests that dietary antioxidants may play a critical role in promoting positive pregnancy outcomes. However, despite the well-documented benefits of individual antioxidants in reducing oxidative stress and associated complications, research investigating the association between overall antioxidant intake-quantified through the composite dietary antioxidant index (CDAI)-and pregnancy health remains scarce. This research fills a critical void by performing a cross-sectional evaluation based on data collected from the National Health and Nutrition Examination Survey (NHANES) covering the years 2007 to 2018. Through an in-depth assessment of the correlation between CDAI and maternal health outcomes, this study aims to offer fresh perspectives on the possible advantages of a well-rounded antioxidant intake throughout pregnancy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A weighted multiple logistic regression analysis was utilized to examine the relationship between CDAI and pregnancy outcomes, controlling for potential confounders. To further explore heterogeneity within the data, subgroup analyses were performed to identify population-specific variations in the observed associations. Additionally, non-linear trends were assessed using smoothing curve fitting techniques, allowing for a more comprehensive examination of potential complex relationships. To pinpoint threshold effects within the dataset, a segmented weighted linear regression model was employed, facilitating the identification of an inflection point where the nature or magnitude of the association may shift. This multi-faceted analytical approach ensures a robust evaluation of the impact of dietary antioxidant intake on pregnancy-related health outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The multivariate logistic regression analysis revealed that higher levels of CDAI were significantly associated with an increased risk of infertility, after adjusting for various potential confounders. Specifically, individuals in the third quartile of CDAI (Q3) exhibited a 2.04-fold increase in the odds of infertility compared to those in the first quartile (OR 2.035, 95% CI 1.243-3.331, p = 0.00471), while those in the fourth quartile (Q4) faced a 3.58-fold greater risk (OR 3.581, 95% CI 2.249-5.700, p &lt; 0.00001). These associations remained significant across subgroups differentiated by age, body mass index (BMI), educational attainment, and family income-to-poverty ratios.Additionally, when CDAI was treated as a continuous variable, a 0.1 unit increase was found to be associated with a more than 7% increase in the odds of achieving pregnancy (OR 1.076, 95% CI 1.042-1.110, p &lt; 0.00001). This relationship highlights the potential impact of antioxidant consumption on reproductive health, indicating that higher antioxidant intake may enhance fertility outcomes. These findings warrant further investigation into the mechanisms by which antioxida","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological Factors Contributing to Health-Related Quality of Life Following Endometriosis Surgery: Results of a Cross-Sectional Study.","authors":"Z Boersen, J M Oosterman, C I M Aalders, D D M Braat, C M Verhaak, A W Nap","doi":"10.1007/s43032-025-01899-3","DOIUrl":"https://doi.org/10.1007/s43032-025-01899-3","url":null,"abstract":"<p><strong>Introduction: </strong>Endometriosis causes severe and chronic pain leading to impaired Health-Related Quality of Life (HRQoL). While endometriosis surgery does improve pain intensity, psychological factors have an important role in pain perception. The current study aims to evaluate the independent contribution of pain catastrophizing and anxiety and depression to HRQoL between six months and nine years following endometriosis surgery.</p><p><strong>Methods: </strong>This is a cross-sectional questionnaire study including women with endometriosis who were surgically treated for endometriosis-related pain. Hierarchical multiple linear regression analysis was used to evaluate the relationship of pain catastrophizing and a total score for anxiety and depression to HRQoL, in addition to the contributions of pain intensity, fatigue and sleep quality. In a sub-analysis, we evaluated this relationship in patients with a shorter and with a longer time since surgery (TSS).</p><p><strong>Results: </strong>The study included 195 participants, revealing significant correlations between HRQoL, pain catastrophizing and anxiety and depression. Subgroup analysis demonstrated that both pain catastrophizing and a combined anxiety and depression score significantly predicted HRQoL in both the shorter and longer TSS groups. These associations were found in addition to the contribution of pain intensity, fatigue and sleep quality to HRQoL.</p><p><strong>Conclusion: </strong>The current study demonstrates that pain catastrophizing and a combination of anxiety and depression contribute to HRQoL in patients six months to nine years after surgical treatment of endometriosis. Extended post-surgical care could be warranted to address these factors accordingly, for example with psychological care, in addition to surgery alone.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometriosis and Ovarian Cancer: Insights from NHANES and Mendelian Randomization Analysis.","authors":"Dong Liu, Yuke Wu, Kunyan Zhou","doi":"10.1007/s43032-025-01910-x","DOIUrl":"https://doi.org/10.1007/s43032-025-01910-x","url":null,"abstract":"<p><p>Endometriosis describes the growth of extra-uterine endometrium, causing pain and inflammation, and the condition has been estimated to affect 10% of women of reproductive age. It remains under-diagnosed and has been linked to increased cancer risk. This study evaluated the correlation between endometriosis and cancer. The significance of specific loci to cancer was analyzed via Mendelian randomization (MR). Of the 4092 samples included, cancer diagnoses were self-reported by 326 women with endometriosis and 3766 women without endometriosis. Correlations between individual cancer types and endometriosis were analyzed by multivariable logistic regression models and odds ratios (OR) adjusted for confounders. Mortality was evaluated by Kaplan-Meier survival analysis. Genetic variants associated with endometriosis were linked to ovarian cancer by MR analysis. Women with endometriosis had a higher association of overall cancer (OR = 1.80, 95% CI: 1.19-2.72) and this was especially the case for ovarian cancer (OR = 11.40, 95% CI: 3.00-43.34). Subgroup and sensitivity analyses confirmed the robustness of these results. Kaplan-Meier analysis indicated lower survival from all causes in women with endometriosis (p = 0.022) but no significant difference in cancer survival. MR analysis supported a positive relationship between endometriosis and ovarian cancer (OR = 1.203, 95% CI: 1.011-1.433). The history of endometriosis was positively associated with the history of overall and ovarian cancer. Women with a history of endometriosis should have access to enhanced cancer surveillance and proactive management. Further research is needed to confirm these associations and to give mechanistic insights.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can a Diet, Nutrition and Supplement Program Prevent Uterine Fibroid Recurrence? Pilot Results of the LIFE Program.","authors":"Margot Bellon, Elaine Salamanca, Steven Friedman, Michael Chan, Taraneh Shirazian","doi":"10.1007/s43032-025-01904-9","DOIUrl":"10.1007/s43032-025-01904-9","url":null,"abstract":"<p><p>The objective of this prospective, longitudinal cohort study was to evaluate the pilot effects of a 24-month exercise and nutrition intervention, called the Lifestyle Intervention for Fibroid Elimination Program (LIFE), at NYU Langone Health's Center for Fibroid Care. Specifically, we evaluate the impact on quality of life (QOL), symptom severity (SS), and clinical lab markers in 22 fibroid patients. Patients who underwent a procedure within 3 months of the start of the LIFE Program and completed up to 12 months of the program were included in this study. Participants were excluded if currently pregnant, postmenopausal, or had dietary restrictions or physical constraints that prevented them from participating fully in the intervention. This intervention required participants to follow a prescribed nutrition and exercise regimen for up to 12 months and attend at least 2 office visits with a physician. Participants also completed two quality of life questionnaires and regular ultrasound imaging. The demographic breakdown of our study cohort was 63.6% Black and 18.2% Hispanic/LatinX. A clinically meaningful improvement in QOL and symptom severity was found within the first year of the LIFE program. The QOL sub-scale scores that showed the greatest improvement were concern and energy/mood. Vitamin D lab values also showed a clinically meaningful improvement. The LIFE Program was associated with a reduction in symptom burden and an improvement in quality of life up to 12 months after a procedural fibroid intervention, yielding insight into how a lifestyle intervention may be an effective adjunct in improving patient quality of life.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of TLR4 Asp299Gly and Thr399Ile Gene Polymorphisms as a Risk Factor in Human Cytomegalovirus Positive Pregnant Women.","authors":"Tanzeem Fatima, Asad Syed, Abdallah M Elgorban, Islem Abid, Ling Shing Wong, Mohd Sajid Khan, Jahanarah Khatoon, Puneet Kumar Sharma","doi":"10.1007/s43032-025-01912-9","DOIUrl":"10.1007/s43032-025-01912-9","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) is the primary cause of intra-uterine infections (human health) affecting 40-100% of pregnant women globally, with lower rates observed in high-income countries and higher rates in low- and middle-income regions, and it is vertically transmitted to fetus. Mutation in the TLR4 gene is known for enhanced predisposition to several viral, bacterial, and parasitic diseases. This study aimed to investigate the correlation between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and vulnerability to HCMV infection in pregnant women. A total of 400 pregnant women, 150 patients infected with HCMV during pregnancy and 250 age-matched control individuals uninfected with virus, age between 18 and 40 years were included in this study. DNA was extracted and PCR was carried out for screening HCMV infection and TLR4 allele-specific polymorphisms using PCR-based genotyping assay. This was achieved by a genotyping procedure that employs PCR. Prevalence rates of genotypes and alleles in TLR4 SNP were calculated; both in the HCMV infected and uninfected pregnant women by means of descriptive statistics. The results suggested that women with a heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms have an increased predisposition to HCMV infection (p = 0.037 and p = 0.024, respectively). Our analysis revealed that individuals with Gly and Ile alleles had a higher susceptibility to HCMV infection (p = 0.013 and p = 0.001, respectively). The IIe/Gly haplotype showed a significant correlation with the probability of illness compared to the control group (p = 0.006). A correlation was also seen between increased TLR4 mRNA expression and HCMV positivity (p = 0.04). Thus, polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) seem to contribute to the occurrence of HCMV infection in pregnant women.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry-Based Untargeted Metabolomics Identifies Distinct Metabolic Signatures in Infertility: A Comparative Analysis of PCOS, POR, and NOR.","authors":"Metin Demirel, Mehtap Alim, Fatmanur Koktasoglu, Nil Atakul, Ebru Guner, Ayse Nur Işık Aydın, Sanem Naz Kafali, Yildız Atamer, Sahabettin Selek","doi":"10.1007/s43032-025-01908-5","DOIUrl":"10.1007/s43032-025-01908-5","url":null,"abstract":"<p><strong>Background: </strong>Infertility affects approximately 15% of reproductive-age couples, with polycystic ovary syndrome and poor ovarian reserve being major contributing factors. Metabolomic profiling of follicular fluid offers insights into the underlying metabolic disturbances associated with these infertility phenotypes. This study aims to identify metabolic biomarkers distinguishing PCOS, POR, and male factor infertility, which may facilitate improved diagnostic and therapeutic strategies.</p><p><strong>Methods: </strong>A total of 119 participants were categorized into three groups: PCOS (n = 39), POR (n = 40), and NOR (n = 40). Liquid chromatography-high-resolution mass spectrometry was used for untargeted metabolomic profiling. Metabolites were identified using HMDB, MassBank, and MoNA, while pathway analysis was performed using KEGG. Statistical analyses were conducted using R and Python, including one-way ANOVA, t-tests, and Mann-Whitney U tests, with False Discovery Rate correction applied.</p><p><strong>Results: </strong>Distinct metabolic alterations were observed among the groups. Trehalose-6-phosphate, taurocholate, and N,N-dimethylglycine emerged as the most significantly altered metabolites, showing strong discriminatory potential between PCOS and POR. PCOS patients exhibited reduced levels of taurocholate, mycalemide, and trehalose-6-phosphate, whereas NOR patients showed elevated levels of N,N-dimethylglycine and argininosuccinate. The POR group demonstrated increased levels of 1-methyl-2-pyrrolidone and haplopine, along with a broader metabolite distribution.</p><p><strong>Conclusion: </strong>This study reveals phenotype-specific metabolic signatures in PCOS and POR, identifying taurocholate, mycalemide, and N,N-dimethylglycine as potential follicular biomarkers. These findings contribute to a deeper understanding of the metabolic basis of infertility and highlight the potential of follicular fluid metabolomics for precision medicine in reproductive health.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Defense/Immunity Proteins in Non-Obstructive Azoospermia: Insights from Gene Expression and Single-Cell RNA Sequencing Analyses.","authors":"Ali Shakeri Abroudi, Hossein Azizi, Melika Djamali, Hewa Khalid Abdullah, Ali Qorbanee, Thomas Skutella","doi":"10.1007/s43032-025-01916-5","DOIUrl":"10.1007/s43032-025-01916-5","url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by a complete absence of sperm in the ejaculate due to impaired spermatogenesis. While genetic and hormonal factors are known contributors, recent evidence highlights the role of immune dysregulation in NOA pathophysiology. Defense/immunity proteins play a crucial role in maintaining testicular immune homeostasis, but their aberrant expression may contribute to spermatogenic failure. This study analyzed gene expression data from multiple datasets to identify immune-related genes significantly altered in NOA, including IFITM1, CES1, MR1, LSAMP, PRB2, CARD8, and PECAM1. Differential expression analysis revealed upregulation of IFITM1 and PECAM1 and downregulation of CES1, MR1, LSAMP, PRB2, and CARD8, suggesting immune imbalance and oxidative stress contribute to NOA pathogenesis. Additionally, single-cell RNA sequencing confirmed their differential expression in distinct testicular cell populations. Our findings suggest that immune-related pathways, including cytokine signaling, antigen processing, and oxidative stress response, may contribute to NOA pathogenesis. Targeting these molecular pathways could provide novel therapeutic strategies for improving reproductive outcomes in affected individuals.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Molecular Aetiology of Cytochrome P450 Oxidoreductase Deficiency Diagnosed in 46,XX Patients.","authors":"Duoduo Zhang, Lelei Ding, Shan Deng, Qinjie Tian","doi":"10.1007/s43032-025-01878-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01878-8","url":null,"abstract":"<p><p>P450 oxidoreductase deficiency (PORD) affects cytochrome enzyme activities, causing various symptoms, such as adrenal insufficiency, disorders of sex development and skeletal malformations. This study aims to elucidate the clinical manifestations, genotype characteristics, diagnosis and management of 46,XX karyotype patients with PORD in China. A retrospective study included twelve 46,XX PORD patients in a Chinese tertiary medical center from 2004 to 2024. The patients' clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments. The age of first visit was 7-31 years. Except for one young girl presenting with ambiguous genitalia since born, 11 patients presented with either abnormal menses or multiple ovarian cysts. Six patients showed masculinization of their external genitalia, and ten patients showed varying degrees of skeletal deformity. Progesterone was elevated and ovarian reserve was poor in all patients. The most frequent POR variant, c.1370G > A, located in exon 11 occurred in 11/12 patients with an allele frequency of 87.5% (21/24). Two novel nonsense mutations, c.1684dupG and c.2040dupC, were identified and assessed as pathogenic and likely pathogenic by ACMG, respectively. The c.1370G > A might be a dominant mutation type of POR in China. Female patients with PORD have a vulnerable ovarian reserve, and their ovarian macrocysts can be managed conservatively for fertility preservation. This study specifically focuses on PORD in 46,XX Chinese individuals, which implies its genetic causes with novel genetic findings and summarizes the puzzling spectrum of clinical manifestations.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Nifedipine in Preventing Ovarian Hyperstimulation Syndrome through TRPC1 Ion Channel Inhibition.","authors":"Emel Kocal, Remzi Atilgan, Şehmus Pala, Melike Aslan, Tuncay Kuloğlu, Nevin Ilhan, Ebru Etem Önalan, Serhat Hançer, Gizem Kaymaz Bircan","doi":"10.1007/s43032-025-01913-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01913-8","url":null,"abstract":"<p><p>Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication that usually develops as a result of triggering ovulation with human chorionic gonadotropin (hCG) after gonadotropin treatment, and in whose pathophysiology vascular endothelial growth factor (VEGF) and inflammatory mediators play a role. Nifedipine, used especially in the treatment of hypertension, is a calcium channel blocker. Nifedipine also has anti-inflammatory effects via transient receptor potential canonical (TRPC1) ion channel inhibition. VEGF also regulates the angiogenic process through TRPC channels. In our study, we investigated the potential of nifedipine to prevent OHSS due to its TRPC1 blocking effect and anti-inflammatory effects. A total of 28 rats were randomly divided into four equal groups. Group (G) 1 control group (n = 7). Rats in G2 (n = 7) were administered 30 IU pregnant mare serum gonadotropin for 4 days and OHSS was induced by administering 30 IU hCG on the fifth day. Rats in G3 (n = 7) were induced to have OHSS and were given 100 μg/kg oral cabergoline, while rats in G4 (n = 7) were induced to have OHSS and were given 20 mg/kg intraperitoneal nifedipine. On the fifth day, all rats were decapitated and VEGF, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and hypoxia-inducible factor (HIF)-1α levels were measured in their serum and tissues. TRPC1 gene expression and immunohistochemical analysis were performed in ovarian tissue. We showed that nifedipine inhibited VEGF and some inflammatory factor levels more than cabergoline. We showed that nifedipine may achieve these effects through TRPC1 blockade and suppression of inflammatory factors.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}