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Stearoyl–coenzyme A desaturase enhances cell survival in human uterine leiomyoma 硬脂酰辅酶A去饱和酶提高人子宫平滑肌瘤细胞存活率。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2025.01.005
Allison S. Komorowski M.D., John S. Coon V M.S., Melania Anton B.S., Azna Zuberi Ph.D., Olivia Sotos B.S., Serdar E. Bulun M.D., Ping Yin M.D., Ph.D.
{"title":"Stearoyl–coenzyme A desaturase enhances cell survival in human uterine leiomyoma","authors":"Allison S. Komorowski M.D.,&nbsp;John S. Coon V M.S.,&nbsp;Melania Anton B.S.,&nbsp;Azna Zuberi Ph.D.,&nbsp;Olivia Sotos B.S.,&nbsp;Serdar E. Bulun M.D.,&nbsp;Ping Yin M.D., Ph.D.","doi":"10.1016/j.xfss.2025.01.005","DOIUrl":"10.1016/j.xfss.2025.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Stearoyl-CoA desaturase (SCD1) is an enzyme that catalyzes the conversion of saturated delta-9 fatty acids to monounsaturated fatty acids. SCD1 is highly expressed in various cancers and facilitates cancer cell survival, tumor growth, and metastasis. This study aimed to assess SCD1 expression and function in uterine leiomyoma and matched myometrial tissue and evaluate the impact of SCD1 inhibition on leiomyoma cell viability and apoptosis.</div></div><div><h3>Design</h3><div>Gene set enrichment analysis was performed to determine whether lipid metabolism pathways are dysregulated in leiomyoma. To assess the function of SCD1, primary leiomyoma and myometrial cells, as well as a CRISPR-engineered leiomyoma-relevant <em>MED12</em> mutant human uterine smooth muscle (UtSM) cell line, were treated with <em>SCD1</em> small interfering RNA or a small molecule inhibitor of SCD1, CAY10566. Cell viability and apoptosis assays, real-time quantitative polymerase chain reaction, and immunoblot analyses were performed to evaluate cell function in response to treatment.</div></div><div><h3>Subjects</h3><div>Leiomyoma and myometrial tissues were obtained from premenopausal individuals designated female at birth (n = 30) undergoing myomectomy or hysterectomy.</div></div><div><h3>Exposure</h3><div>SCD1 inhibition by small interfering RNA and CAY10566 treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Messenger RNA (mRNA) and protein levels and cell viability and apoptosis.</div></div><div><h3>Results</h3><div>Gene set enrichment analysis revealed that the cholesterol homeostasis pathway was significantly different in leiomyoma vs. adjacent myometrial tissues. Among the genes in this pathway, SCD1 mRNA levels were found to be significantly higher in leiomyoma than in matched myometrium. SCD1 inhibition by small interfering RNA or CAY10566 decreased antiapoptotic BCL2 mRNA and protein levels and cell viability in primary leiomyoma but not myometrial cells. SCD1 protein levels were significantly higher in the mutant MED12 UtSM cell line than in the wild-type MED12 UtSM cell line. CAY10566 treatment specifically decreased cell viability and increased apoptosis in mutant MED12 UtSM cells, with increased protein levels of cleaved caspase 3, cleaved PARP, and DDIT3 in mutant MED12 UtSM but not in wild-type MED12 UtSM cells.</div></div><div><h3>Conclusion</h3><div>SCD1, an enzyme involved in lipid homeostasis, may play an important role in promoting leiomyoma growth and represents a novel target for the treatment of leiomyoma.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 202-212"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug-free in vitro activation of ovarian follicles and fresh tissue autotransplantation in patients with poor ovarian response and premature ovarian insufficiency. 卵巢反应差和卵巢功能不全患者的无药体外激活卵泡和新鲜组织自体移植。
F&S science Pub Date : 2025-04-30 DOI: 10.1016/j.xfss.2025.04.002
Leonti Grin, Roza Berkovitz-Shperling, Gal Goldstein, Yulia Michailov, Ofer Gemer, Eyal Anteby, Kazuhiro Kawamura, Bozhena Saar-Ryss, Shevach Friedler
{"title":"Drug-free in vitro activation of ovarian follicles and fresh tissue autotransplantation in patients with poor ovarian response and premature ovarian insufficiency.","authors":"Leonti Grin, Roza Berkovitz-Shperling, Gal Goldstein, Yulia Michailov, Ofer Gemer, Eyal Anteby, Kazuhiro Kawamura, Bozhena Saar-Ryss, Shevach Friedler","doi":"10.1016/j.xfss.2025.04.002","DOIUrl":"10.1016/j.xfss.2025.04.002","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether drug-free in vitro activation (IVA) with immediate autotransplantation improves reproductive outcomes and ovarian blood flow in patients with poor ovarian response (POR) and premature ovarian insufficiency (POI).</p><p><strong>Design: </strong>A clinical trial.</p><p><strong>Setting: </strong>A tertiary university-affiliated hospital.</p><p><strong>Patient(s): </strong>Twenty-one women diagnosed with POR (n = 7) and POI (n = 14).</p><p><strong>Intervention(s): </strong>Drug-free IVA through mechanical ovarian tissue disruption and immediate autotransplantation.</p><p><strong>Main outcome measure(s): </strong>Changes in antral follicle count, antimüllerian hormone levels, ovarian volume, Doppler indices, oocyte retrieval rates, and embryo cryopreservation.</p><p><strong>Result(s): </strong>After drug-free IVA, the antral follicle count increased in 71% of patients with POR and 50% of patients with POI, whereas the antimüllerian hormone levels improved in 57% of patients with POR and 7% of patients with POI. A significant increase in ovarian volume was noted in patients with POR and in patients with POI who exhibited follicle growth after IVA. Doppler indices revealed no significant changes in ovarian blood flow. Follicle development was achieved in all patients with POR and 10 of 14 patients with POI, facilitating successful oocyte retrieval in all patients with POR and 7 of 14 patients with POI. The fertilization rates were 72% and 59% for patients with POR and POI, respectively. All patients with POR and 5 of 14 patients with POI had at least 1 embryo cryopreserved. Among the 11 patients who underwent frozen embryo transfer, 2 clinical pregnancies were achieved, resulting in 1 live birth.</p><p><strong>Conclusion(s): </strong>Drug-free IVA demonstrates potential in improving follicular activity, oocyte retrieval, and embryo cryopreservation. However, clinical application remains challenging due to modest success rates, necessitating further protocol refinements and long-term outcome evaluations.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (Identifier: NCT04024722).</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the molecular cross-talk between piwi-interacting RNAs and steroid 5 alpha reductase type 2 in sperm dysfunction. 揭示精子功能障碍中piwi相互作用rna与类固醇5 α还原酶2型之间的分子串扰。
F&S science Pub Date : 2025-04-29 DOI: 10.1016/j.xfss.2025.03.007
Adnan Fadhel Al-Azaawie, Ahmed AbdulJabbar Suleiman, Mousa Jasim Mohammed
{"title":"Unveiling the molecular cross-talk between piwi-interacting RNAs and steroid 5 alpha reductase type 2 in sperm dysfunction.","authors":"Adnan Fadhel Al-Azaawie, Ahmed AbdulJabbar Suleiman, Mousa Jasim Mohammed","doi":"10.1016/j.xfss.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.03.007","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the correlation between piwi-interacting RNA (piRNA) expression and steroid 5 alpha reductase type 2 (SRD5A2) mRNA regulation in seminal fluid across various male infertility conditions (asthenozoospermia, oligozoospermia, and azoospermia).</p><p><strong>Design and subjects: </strong>This study included 88 male participants aged 20-40 years, categorized into infertility and normozoospermic groups.</p><p><strong>Exposure: </strong>Seminal fluid analysis and RNA extraction were performed to quantify SRD5A2 mRNA and selected piRNAs (hsa-piR-002528, hsa-piR-017183, hsa-piR-023244, and hsa-piR-023338) using qRT-PCR.</p><p><strong>Main outcome measures: </strong>Correlation analysis evaluated interactions between piRNA levels and SRD5A2 expression. Statistical significance was determined using analysis of variance and correlation coefficients.</p><p><strong>Results: </strong>Seminal Fluid Analysis: significant differences in seminal volume, sperm morphology, count, and motility were observed across infertility subtypes. Steroid 5 alpha reductase type 2 Expression: asthenozoospermia showed up-regulated SRD5A2 mRNA (Log2FC = 0.333), whereas oligozoospermia and azoospermia exhibited down-regulation (Log2FC = -0.470 and -0.688, respectively). Piwi-interacting RNA Expression: hsa-piR-002528 and hsa-piR-017183 were up-regulated in all infertility subtypes, whereas hsa-piR-023244 and hsa-piR-023338 exhibited subtype-specific expression patterns. Correlation Analysis: Steroid 5 alpha reductase type 2 mRNA negatively correlated with hsa-piR-002528 and hsa-piR-023338, suggesting regulatory interactions affecting sperm motility and count. Positive correlations were observed for hsa-piR-023244 in azoospermia, indicating potential roles in supporting spermatogenesis.</p><p><strong>Conclusions: </strong>Altered piRNA profiles and SRD5A2 expression are associated with male infertility subtypes. These findings highlight the regulatory role of piRNAs in spermatogenesis and their potential as biomarkers and therapeutic targets for male infertility.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of CYP19A1 genetic variations on polycystic ovary syndrome: findings from a case-control study. CYP19A1基因变异对多囊卵巢综合征的影响:一项病例对照研究的结果
F&S science Pub Date : 2025-03-28 DOI: 10.1016/j.xfss.2025.03.005
Hiral Chaudhary, Jalpa Patel, Nayan K Jain, Sonal Panchal, Purvi Nanavati, Mala Singh, Naresh Laddha, Rushikesh Joshi
{"title":"Impact of CYP19A1 genetic variations on polycystic ovary syndrome: findings from a case-control study.","authors":"Hiral Chaudhary, Jalpa Patel, Nayan K Jain, Sonal Panchal, Purvi Nanavati, Mala Singh, Naresh Laddha, Rushikesh Joshi","doi":"10.1016/j.xfss.2025.03.005","DOIUrl":"10.1016/j.xfss.2025.03.005","url":null,"abstract":"<p><strong>Objective: </strong>To study the association between CYP19A1 genetic variants and the risk of developing polycystic ovary syndrome (PCOS). The study explored the relationship between the candidate gene CYP19A1 and hyperandrogenism, as well as its interplay with obesity, in PCOS patients compared with healthy controls.</p><p><strong>Design: </strong>A case-control study with genetic association analysis by tetra-primer amplification refractory mutation system polymerase chain reaction and biochemical analysis.</p><p><strong>Subjects: </strong>204 women (113 PCOS patients and 91 healthy controls) were included in the present study.</p><p><strong>Exposure: </strong>CYP19A1 variants (rs700519 and rs2236722) in PCOS women.</p><p><strong>Main outcome measures: </strong>Genotypic and allelic frequencies of CYP19A1 variants (rs2236722 and rs700519) and their impact on androgen metabolism and obesity markers.</p><p><strong>Results: </strong>The genotypic and allelic frequency of rs2236722 showed statistically significant differences between PCOS cases and controls. A significant association was observed under the dominant model, with an odds ratio of 0.34 (95% confidence interval, 0.16-0.66), as well as under the heterozygous model, where the odds ratio was 2.58 (95% confidence interval, 1.34-4.97). However, rs700519 did not reveal any significant association between the groups. A noticeable statistical difference was observed in the levels of total testosterone, dehydroepiandrosterone sulfate , prolactin, luteinizing hormone/follicle-stimulating hormone , Estradiol/total testosterone ratio, body mass index, and waist-to-hip ratio between the case and control groups . However, no variations in clinical variables were observed among genotypes within the PCOS group.</p><p><strong>Conclusion: </strong>Our study demonstrates that the CYP19A1 rs2236722 polymorphism significantly correlates with PCOS risk, although rs700519 showed no significant association. The findings suggest that altered aromatase activity linked to rs2236722 may contribute to the hyperandrogenic phenotype observed in PCOS patients. These results enhance our understanding of the genetic basis of PCOS and may have implications for personalized treatment approaches.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of ethnicity and polycystic ovary syndrome on pregnancy complications: an analysis of a population database. 种族与多囊卵巢综合征对妊娠并发症的影响。人口数据库的分析。
F&S science Pub Date : 2025-03-27 DOI: 10.1016/j.xfss.2025.03.004
Magdalena Peeva, Ahmad Badeghiesh, Haitham Baghlaf, Michael H Dahan
{"title":"The role of ethnicity and polycystic ovary syndrome on pregnancy complications: an analysis of a population database.","authors":"Magdalena Peeva, Ahmad Badeghiesh, Haitham Baghlaf, Michael H Dahan","doi":"10.1016/j.xfss.2025.03.004","DOIUrl":"10.1016/j.xfss.2025.03.004","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine the independent effect of ethnicity on obstetric outcomes in women with polycystic ovary syndrome (PCOS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;This was a retrospective, population-based cohort study using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2004 to 2014. Women with PCOS were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Pregnancy, delivery, and neonatal outcomes were compared across ethnic groups. The chi-square tests assessed baseline characteristics, and logistic regression was used to evaluate associations between ethnicity and outcomes, estimating odds ratios (ORs) and 95% confidence intervals (CIs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Subjects: &lt;/strong&gt;A total of 12,782 pregnant women with PCOS were identified between 2004 and 2014, categorized by ethnicity: White (n = 9,107); African American (n = 1,098); Hispanic (n = 1,288); and Asian (n = 741).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;The exposure of interest was maternal ethnicity and its association with pregnancy, delivery, and neonatal outcomes among women with PCOS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;Pregnancy, delivery, and neonatal complications were assessed across ethnic groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Asian women had a higher odds of having gestational diabetes (adjusted OR [aOR], 1.96; 95% CI, 1.49-2.58), chorioamnionitis (aOR, 3.41; 95% CI, 2.12-5.47), operative vaginal delivery (aOR, 2.42; 95% CI, 1.65-3.56), postpartum hemorrhage (PPH) (aOR, 2.07; 95% CI, 1.25-3.43), and maternal infection (aOR, 2.84; 95% CI, 1.80-4.49). African Americans had a higher risk of pregnancy-induced hypertension (aOR, 1.38; 95% CI, 1.06-1.80), preeclampsia (aOR, 1.68; 95% CI, 1.15-2.45), preterm premature rupture of membrane (aOR, 2.75; 95% CI, 1.58-4.78), chorioamnionitis (aOR, 1.83; 95% CI, 1.12-2.98), and cesarean sections (aOR, 1.69; 95% CI, 1.32-2.15) and lower risk of operative vaginal delivery (aOR, 0.53; 95% CI, 0.31-0.93), spontaneous vaginal delivery (aOR, 0.67; 95% CI, 0.52-0.85), and maternal infection (aOR, 1.91; 95% CI, 1.21-3.00). The risk of gestational diabetes (aOR, 1.36; 95% CI, 1.06-1.73) and PPH (aOR, 1.58; 95% CI, 1.01-2.47) increased among Hispanic patients. Caucasian patients were at lower risk of gestational diabetes (aOR, 0.67; 95% CI, 0.57-0.79), chorioamnionitis (aOR, 0.39; 95% CI, 0.28-0.55), cesarean section (aOR, 0.83; 95% CI, 0.73-0.95), PPH (aOR, 0.70; 95% CI, 0.50-0.98), blood transfusion (aOR, 0.49; 95% CI, 0.29-0.83), maternal infection (aOR, 0.34; 95% CI, 0.27-0.51), and small-for-gestational-age infants (aOR, 0.64; 95% CI, 0.44-0.93) and had higher odds of having a spontaneous vaginal delivery (aOR, 1.25; 95% CI, 1.10-1.43).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Among women with PCOS, African Americans have the highest number of increased pregnancy complications, followed by Asians and Hispanics. Caucasians with PCOS have t","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling familial ties: elevated sperm DNA fragmentation index in men with infertility and familial cancer susceptibility. 揭示家族关系:不育男性精子DNA断裂指数升高与家族性癌症易感性。
F&S science Pub Date : 2025-03-22 DOI: 10.1016/j.xfss.2025.03.002
Federico Belladelli, Riccardo Ramadani, Marco Malvestiti, Edoardo Pozzi, Christian Corsini, Massimiliano Raffo, Fausto Negri, Alessandro Bertini, Simone Cilio, Luca Boeri, Massimo Alfano, Giovanni Lavorgna, Alessia d'Arma, Francesco Montorsi, Andrea Salonia
{"title":"Unraveling familial ties: elevated sperm DNA fragmentation index in men with infertility and familial cancer susceptibility.","authors":"Federico Belladelli, Riccardo Ramadani, Marco Malvestiti, Edoardo Pozzi, Christian Corsini, Massimiliano Raffo, Fausto Negri, Alessandro Bertini, Simone Cilio, Luca Boeri, Massimo Alfano, Giovanni Lavorgna, Alessia d'Arma, Francesco Montorsi, Andrea Salonia","doi":"10.1016/j.xfss.2025.03.002","DOIUrl":"10.1016/j.xfss.2025.03.002","url":null,"abstract":"<p><strong>Objective: </strong>To study the potential association between pure male factor infertility (MFI) and the likelihood of a positive family history of cancer because limited information exists on the oncologic risk among relatives of men experiencing infertility.</p><p><strong>Design: </strong>This cross-sectional, retrospective analysis considered the latest 1,168 men seeking medical help for primary couple's infertility at a single center. Infertility was defined according to the World Health Organization criteria.</p><p><strong>Subjects: </strong>A total of 1,168 men seeking medical help for primary couple's infertility at a single center.</p><p><strong>Intervention(s): </strong>Patients underwent thorough assessments, including medical history, measured body mass index, laboratory investigations including semen analyses and sperm DNA fragmentation (SDF) index testing.</p><p><strong>Main outcome measure(s): </strong>Abnormal SDF was defined as >30%. Descriptive statistics and logistic regression analyses tested the association between semen parameters, SDF, and positive cancer family history.</p><p><strong>Result(s): </strong>Of 1,168, 168 (14.4%) patients reported a positive cancer familial history. Patients with positive cancer family history were older (median interquartile range [IQR]: 37.00 [33.00-41.00] vs. 38.00 [34.00-41.00] years) and more frequently smokers (271 [27.1] vs. 64 [38.1]). Positive family history for malignancies was observed in 79 (40.9%), 66 (34.2%), 36 (18.7%), and 6 (3.1%) patients with a 1st, 2nd, 3rd, and 4th degree of kinship, respectively. At multivariable logistic regression analysis, SDF was positively associated with an increased risk of positive cancer family history in any (HR, 1.12; 95% CI, 1.04-2.1) and in 1st-degree relatives (HR, 1.01; 95% CI, 1.00-1.03). Similarly, abnormal SDF was associated with an increased risk of positive cancer family history in any relative (HR, 1.78; 95% CI, 1.12-2.87) and in 1st-degree relatives (HR, 1.92; 95% CI, 1.01-3.84).</p><p><strong>Conclusion: </strong>Almost 14% of patients with MFI reported a familial history of cancer. Greater SDF levels emerged to be associated with a higher likelihood of a positive family history of cancer.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Utilization of a three-dimensional in vitro co-culture system to characterize embryonic mechanisms associated with implantation. 利用三维体外共培养系统,描述与植入相关的胚胎机制。
F&S science Pub Date : 2025-03-19 DOI: 10.1016/j.xfss.2025.03.001
Keelee J McCarty, Blair McCallie, William B Schoolcraft, Mandy Katz-Jaffe
{"title":"Utilization of a three-dimensional in vitro co-culture system to characterize embryonic mechanisms associated with implantation.","authors":"Keelee J McCarty, Blair McCallie, William B Schoolcraft, Mandy Katz-Jaffe","doi":"10.1016/j.xfss.2025.03.001","DOIUrl":"10.1016/j.xfss.2025.03.001","url":null,"abstract":"<p><strong>Objective: </strong>Implantation success is dependent on timely molecular signaling to establish embryonic apposition, adhesion, and invasion. In an effort to elucidate this critical period in human reproduction, the objective of this study was to use a novel, time-lapse three-dimensional (3D) in vitro co-culture system to characterize the timing of blastocyst development on the initial stages of implantation.</p><p><strong>Design: </strong>Endometrial biopsies were collected from fertile oocyte donors to generate individual 3D wells of separated monolayers of luminal endometrial epithelial and stromal cells for co-culture with an individual blastocyst (n = 72; maternal age = 36.3 ± 5.1 years). After 72 hours of co-culture (CytoSMART Lux3 time-lapse imaging system), blastocysts were evaluated for stage of implantation and separated into two groups: No implantation (no adhesion or invasion) and implantation (complete adhesion and invasion).</p><p><strong>Subjects: </strong>N/A.</p><p><strong>Intervention: </strong>N/A.</p><p><strong>Main outcome measures: </strong>Immunohistochemistry and targeted quantitative real-time polymerase chain reaction gene expression were performed on individual blastocysts and on exosome-purified small RNAs derived from supernatant.</p><p><strong>Results: </strong>After successful implantation into the endometrial epithelium, correctly timed blastocysts experienced greater duration of apposition and adhesion, delayed onset of invasion, and increased number of spontaneous blastocyst collapse compared with slower developing blastocysts. Additionally, targeted gene expression analysis revealed an upward trend of implantation-promoting genes GATA binding protein 3, octamer binding transcription factor 4, and cell death regulatory gene caspase protein 3 in correctly timed blastocysts compared with slower developing blastocysts. Interestingly, as blastocysts became more attached to the epithelium, a downward trend of developmental genes caudal-related homeobox 2 and bone morphogenic protein 15 was observed. A downward trend of hsa-miR-1-3p and an upward trend of hsa-miR-34b-5p was observed in the supernatant of co-cultured blastocysts that achieved successful implantation in co-culture. Top Kyoto Encyclopedia of Genes and Genomes pathways impacted by these microRNAs were axon guidance, ubiquitin-mediated proteolysis, and neurotrophin signaling pathway.</p><p><strong>Conclusion: </strong>Time-lapse 3D in vitro co-culture revealed that the timing of blastocyst development is critical to the initial stages of implantation. The ability of the trophectoderm to expand, orient, and initiate apposition may contribute to the higher likelihood of success as indicated by altered gene expression and regulatory pathways.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The dual nature of micronutrients on fertility: too much of a good thing? 微量元素对生育能力的双重性质:过量是件好事?
F&S science Pub Date : 2025-02-25 DOI: 10.1016/j.xfss.2025.02.004
Aron Moazamian, Elisa Hug, Pauline Villeneuve, Stéphanie Bravard, Richard Geurtsen, Jorge Hallak, Fabrice Saez, Robert John Aitken, Parviz Gharagozloo, Joël R Drevet
{"title":"The dual nature of micronutrients on fertility: too much of a good thing?","authors":"Aron Moazamian, Elisa Hug, Pauline Villeneuve, Stéphanie Bravard, Richard Geurtsen, Jorge Hallak, Fabrice Saez, Robert John Aitken, Parviz Gharagozloo, Joël R Drevet","doi":"10.1016/j.xfss.2025.02.004","DOIUrl":"10.1016/j.xfss.2025.02.004","url":null,"abstract":"<p><strong>Objective: </strong>To study the effects of generally considered safe doses of antioxidant micronutrient supplementation on semen parameters, systemic redox balance, sperm DNA structural integrity, and fertility.</p><p><strong>Design: </strong>Given ethical limitations in human studies, this dose escalation study examined the effects of common water-soluble antioxidant micronutrients (vitamin C, zinc, folate, and carnitine) on semen parameters, redox status, DNA integrity, and fertility outcomes in healthy male mice over one spermatogenic cycle. The study was partially repeated at the highest carnitine dose for pregnancy outcomes and comparatively assessed in subfertile, oxidatively stressed mice.</p><p><strong>Subjects: </strong>\"Fertile/healthy\" (CD1) and \"Subfertile/oxidatively stressed\" (gpx5<sup>-/-</sup>) mice.</p><p><strong>Exposure: </strong>Water-soluble micronutrients (vitamin C, zinc, folate, and carnitine).</p><p><strong>Intervention: </strong>N/A MAIN OUTCOME MEASURES: Sperm parameters included count, motility, viability, and acrosome integrity. Systemic redox status was evaluated in blood, measuring malondialdehyde, thiol levels, and total antioxidant capacity. Sperm DNA parameters were examined for oxidation (8-OHdG staining), fragmentation (TUNEL), and decondensation (toluidine blue). Pregnancy outcomes were also assessed in CD1 mice fed carnitine.</p><p><strong>Results: </strong>In healthy mice, increasing doses of individual micronutrients had minimal effects on semen parameters. However, high doses of all four micronutrients significantly disrupted the redox balance in blood plasma and compromised sperm DNA integrity in an ingredient-specific manner. Moderate to high doses of carnitine caused severe DNA fragmentation, a finding confirmed in a subsequent experiment using the highest carnitine dose. In this follow-up experiment, male mice supplemented with carnitine and mated with females showed decreased pregnancy rates and fewer total pups born. Conversely, in oxidatively stressed mice, high-dose carnitine had the opposite, beneficial effect of improving sperm DNA integrity.</p><p><strong>Conclusions: </strong>At high doses, antioxidants can induce reductive stress, damaging vital molecular components of sperm cells such as DNA. Although strong evidence supports the use of preconception antioxidants to boost semen quality, healthcare professionals should assess oxidative stress levels when possible and recommend personalized antioxidant doses to avoid reductive stress and prevent adverse reproductive outcomes.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bupropion, the atypical antidepressant used in smoke cessation: an in vitro study on its effects on human sperm function. 安非他酮,用于戒烟的非典型抗抑郁药:对人类精子功能影响的体外研究。
F&S science Pub Date : 2025-02-25 DOI: 10.1016/j.xfss.2025.02.006
Maria Brito, Ana Gonçalves, Alberto Barros, Mário Sousa, Rosália Sá
{"title":"Bupropion, the atypical antidepressant used in smoke cessation: an in vitro study on its effects on human sperm function.","authors":"Maria Brito, Ana Gonçalves, Alberto Barros, Mário Sousa, Rosália Sá","doi":"10.1016/j.xfss.2025.02.006","DOIUrl":"10.1016/j.xfss.2025.02.006","url":null,"abstract":"<p><strong>Objective: </strong>To assess the effects of the active metabolite of Bupropion, hydroxybupropion, on human spermatozoa in vitro.</p><p><strong>Design: </strong>Laboratory based in vitro study.</p><p><strong>Patients: </strong>Human sperm samples were collected from 45 normozoospermic patients (smokers and nonsmokers).</p><p><strong>Exposure: </strong>Sperm samples were incubated at 37°C with 5% CO<sub>2</sub> for 2 hours with and without the IC<sub>50</sub> concentration of hydroxybupropion (1.9 μM).</p><p><strong>Main outcome measures: </strong>Several sperm analysis were performed, including vitality, motility, chromatin condensation, DNA fragmentation, oxidative stress, mitochondria membrane potential, and acrosome integrity. High-speed video microscopy and Computer-Assisted Sperm Analysis provided a detailed evaluation of sperm motility.</p><p><strong>Results: </strong>Hydroxybupropion exposure resulted in significant impairments in sperm vitality and motility, particularly in progressive motility. Chromatin condensation was significantly reduced, whereas DNA fragmentation, especially in the equatorial region, significantly increased. Mitochondria membrane potential, acrosomal integrity, and reactive oxygen species production also significantly decreased after exposure.</p><p><strong>Conclusion: </strong>The findings indicate potential harm to sperm parameters, which may contribute to infertility. Understanding how Bupropion affects reproductive function is crucial for clinicians and patients to make informed decisions regarding the use of this medication.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From the Editor-in-Chief 来自总编辑。
F&S science Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2025.01.001
William H. Catherino MD, PhD
{"title":"From the Editor-in-Chief","authors":"William H. Catherino MD, PhD","doi":"10.1016/j.xfss.2025.01.001","DOIUrl":"10.1016/j.xfss.2025.01.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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