F&S sciencePub Date : 2025-04-04DOI: 10.1016/j.xfss.2025.04.001
William H Catherino
{"title":"From the Editor-in-Chief.","authors":"William H Catherino","doi":"10.1016/j.xfss.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.04.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797057","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}
F&S sciencePub Date : 2025-03-28DOI: 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":"https://doi.org/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 PCOS. The study explored the relationship between the candidate gene CYP19A1 and hyperandrogenism, as well as its interplay with obesity, in PCOS patients compared to healthy controls.</p><p><strong>Design: </strong>A case-control study with Genetic association analysis by Tetra ARMS PCR 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>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 (p<0.002 and p<0.06, respectively). A significant association was observed under the dominant model, with an odds ratio of 0.34 (95% CI: 0.16-0.66, p = 0.002), as well as under the heterozygous model, where the odds ratio was 2.58 (95% CI: 1.34-4.97, p = 0.003). However, rs700519 did not reveal any significant association between the groups. A noticeable statistical difference was observed in the levels of total testosterone, DHEAS, PRL, LH/FSH, E2/T ratio, BMI, and WHR between the case and control groups (p<0.05). 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, while 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}
F&S sciencePub Date : 2025-03-28DOI: 10.1016/j.xfss.2025.03.006
Javier Guerrero-Sánchez, Andrea Fernández-Toribio, Beatriz Galiano-Cogolludo, Tania García-Martínez, Lucía Mendoza, Gonzalo Fernández-Blanco, Jesús Ramos-Membrive, Joana Fidalgo, Lionel Matthys, José Antonio Horcajadas, Santiago Munné, Pablo Bermejo-Álvarez
{"title":"Kinetics of cell shrinkage and developmental competence of mouse zygotes vitrified following conventional or automated (DaVitri) protocols.","authors":"Javier Guerrero-Sánchez, Andrea Fernández-Toribio, Beatriz Galiano-Cogolludo, Tania García-Martínez, Lucía Mendoza, Gonzalo Fernández-Blanco, Jesús Ramos-Membrive, Joana Fidalgo, Lionel Matthys, José Antonio Horcajadas, Santiago Munné, Pablo Bermejo-Álvarez","doi":"10.1016/j.xfss.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.03.006","url":null,"abstract":"<p><strong>Objective: </strong>To test the developmental ability of murine zygotes vitrified using a novel vitrification device and microfluidic chip (DaVitri®, Overture Life).</p><p><strong>Design: </strong>Murine zygotes were randomly allocated to two groups, one was vitrified using the vitrification device and the other following a conventional manual protocol.</p><p><strong>Subjects: </strong>Murine zygotes obtained in vivo.</p><p><strong>Exposure: </strong>Automatic vitrification was achieved by a linear exposure to cryoprotectants using DaVitri device. Manual vitrification was conducted using Kitazato® kit.</p><p><strong>Main outcome measures: </strong>Morphokinetic behavior of the zygotes during the exposure to cryoprotectants analyzed by microscopy, developmental rates following thawing, lineage development at the blastocyst stage assessed by immunohistochemistry and light-structured fluorescent microscopy, and survival rates and pup weight following embryo transfer.</p><p><strong>Results: </strong>Automated vitrification led to a gradual reduction in zygote volume during the equilibration steps preceding ultra-fast cooling in liquid nitrogen, as opposed to the conventional manual protocol where sharp changes in zygote volume were observed as a result of exposure to static concentrations of cryoprotectants. Survival rates of the automated procedure were comparable to those of the manual protocol, resulting in ∼95% blastocyst formation rates. Developmental analysis of the resulting blastocysts revealed comparable numbers of total, trophectoderm and inner cell mass numbers in blastocysts developed from zygotes vitrified under the manual and automated protocols. No differences were found in survival to term or pup weight a D1 or D21.</p><p><strong>Conclusion: </strong>Automated vitrification using DaVitri device diminished the osmotic stress caused by exposure to CPAs during the equilibration steps and resulted in comparable developmental competence in terms of development to blastocysts, lineage segregation and survival to term.</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":"143756321","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}
F&S sciencePub Date : 2025-03-27DOI: 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":"https://doi.org/10.1016/j.xfss.2025.03.004","url":null,"abstract":"<p><strong>Objective: </strong>To determine the independent effect of ethnicity on obstetrical outcomes in women with polycystic ovary syndrome (PCOS).</p><p><strong>Design: </strong>This was a retrospective, population-based cohort study utilizing data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) from 2004 to 2014. Women with PCOS were identified using ICD-9-CM codes. Pregnancy, delivery, and neonatal outcomes were compared across ethnic groups. 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).</p><p><strong>Subjects: </strong>A total of 12,782 pregnant women with PCOS were identified between 2004 and 2014, categorized by ethnicity: Caucasian (n=9,107), African American (n=1,098), Hispanic (n=1,288), and Asian (n=741).</p><p><strong>Exposure: </strong>The exposure of interest was maternal ethnicity and its association with pregnancy, delivery, and neonatal outcomes among women with PCOS.</p><p><strong>Main outcomes: </strong>Pregnancy, delivery, and neonatal complications were assessed across ethnic groups.</p><p><strong>Results: </strong>Asian women had a higher odds of having gestational diabetes (aOR1.96,95%CI 1.49-2.58,p<0.001), chorioamnionitis (aOR3.41, 95%CI 2.12-5.47,p<0.0001), operative vaginal delivery (aOR2.42, 95%CI 1.65-3.56,p<0.001), postpartum hemorrhage (aOR2.07,95%CI 1.25-3.43,p=0.004) and maternal infection (aOR2.84,95%CI 1.80-4.49,p<0.001). African Americans had a higher risk of pregnancy-induced hypertension (aOR1.38,95% CI 1.06-1.80,p=0.02), preeclampsia (aOR1.68,95% CI 1.15-2.45,p=0.007), preterm premature rupture of membrane (aOR2.75,95%CI 1.58-4.78,p<0.001), chorioamnionitis (aOR1.83 95%CI 1.12-2.98,p=0.016) and cesarean sections (aOR1.69,95%CI 1.32-2.15,p<0.001) and lower risk of operative vaginal delivery (aOR0.53,95%CI 0.31-0.93,p=0.03), spontaneous vaginal delivery (aOR0.67,95%CI 0.52-0.85,p<0.001), and maternal infection (aOR1.91,95%CI 1.21-3.00,p=0.005). The risk of gestational diabetes (aOR1.36,95%CI 1.06-1.73,p<0.014) and postpartum hemorrhage (aOR1.58,95%CI 1.01-2.47,p=0.045) was increased among Hispanic patients. Caucasian patients were at lower risk of gestational diabetes (aOR0.67,95%CI 0.57-0.79,p<0.0001), chorioamnionitis (aOR0.39,95%CI 0.28-0.55,p<0.0001), cesarean section (aOR0.83,95%CI 0.73-0.95,p<0.008), postpartum hemorrhage (aOR0.70,95% CI0.50-0.98,p<0.035), blood transfusion (aOR0.49,95%CI 0.29-0.83,p<0.007), maternal infection (aOR0.34,95% CI 0.27-0.51,p<0.0001) and small for gestational age infants (aOR0.64,95%CI 0.44-0.93,p<0.018), and had higher odds of having a spontaneous vaginal delivery (aOR1.25,95% CI1.10-1.43,p<0.001).</p><p><strong>Conclusions: </strong>Among women with PCOS, African Americans are at the greatest's number of increased pregnancy complications, followed by Asians and then Hispani","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}
F&S sciencePub Date : 2025-03-25DOI: 10.1016/j.xfss.2025.03.003
Varsha Jain, Emi Hojo, Graham McKillop, Anca Oniscu, Yuan Le, Jun Chen, Richard Ehman, Neil Roberts, Hilary Od Critchley
{"title":"Feasibility study of the application of Magnetic Resonance Elastography (MRE) to diagnose adenomyosis.","authors":"Varsha Jain, Emi Hojo, Graham McKillop, Anca Oniscu, Yuan Le, Jun Chen, Richard Ehman, Neil Roberts, Hilary Od Critchley","doi":"10.1016/j.xfss.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.03.003","url":null,"abstract":"<p><strong>Objective: </strong>Magnetic Resonance Elastography (MRE), a novel imaging technique that allows in vivo measurement of tissue mechanical properties, was used to test the prediction that the stiffness of the uterus may be increased due to fibrotic changes in patients with adenomyosis.</p><p><strong>Design: </strong>A feasibility study in which a 3D MRE imaging protocol was developed to measure the stiffness of the tissues of the uterus.</p><p><strong>Subjects: </strong>Four patients with suspected adenomyosis and heavy menstrual bleeding (HMB) diagnosed via transvaginal ultrasound and clinical history and one healthy control were recruited. Two patients underwent hysterectomy and histological analysis of the tissue samples was performed.</p><p><strong>Main outcome measures: </strong>The stiffness of the whole uterus was obtained by Region of Intertest (ROI) analysis of the 3D MRE images for the four patients and one healthy control. In addition for the two patients who underwent hysterectomy the uterine tissue samples were assessed to determine (i) histological presence of adenomyosis via H&E staining, (ii) cellular/molecular measures of tissue stiffness (collagen [picrosirius red], α-smooth muscle actin, e-cadherin) and (iii) if a relationship exists between in vivo assessment of the uterus via 3D MRE and in vitro uterine tissue histology.</p><p><strong>Results: </strong>3D MRE was successfully used to acquire elastograms for four patients with adenomyosis (diffuse n=3, focal n=1) and one healthy volunteer. Calculated global uterine stiffness was higher in women with adenomyosis (2.93 kPa; range 2.34 - 3.39 kPa) compared to the healthy volunteer (2.04 kPa). Regions of high stiffness on the 3D elastograms reflected adenomyotic changes visualised via conventional MRI, and correlated with histological and immunohistochemical markers of tissue stiffness.</p><p><strong>Conclusion: </strong>3D MRE has the potential to provide non-invasive characterisation of changes in the mechanical properties of uterine tissue that is not possible using conventional MRI, or transvaginal ultrasound. Further studies are needed to confirm the efficacy of the 3D MRE protocol for diagnosing adenomyosis.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733488","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}
F&S sciencePub Date : 2025-03-25DOI: 10.1016/j.xfss.2025.02.005
William H Catherino
{"title":"Corrigendum to \"From the Editor-in-Chief\" (F S Sci 2025;6:1-3).","authors":"William H Catherino","doi":"10.1016/j.xfss.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.02.005","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702360","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}
F&S sciencePub Date : 2025-03-21DOI: 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 infertile men 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":"https://doi.org/10.1016/j.xfss.2025.03.002","url":null,"abstract":"<p><p>Structured Abstract OBJECTIVE: To study the potential association between pure male factor infertility (MFI) and the likelihood of a positive family history of cancer, since limited information exists on the oncological risk among relatives of men experiencing infertility.</p><p><strong>Design: </strong>This cross-sectional, retrospective analysis considered the latest 1168 men seeking medical help for primary couple's infertility at a single centre. Infertility was defined according to the WHO criteria.</p><p><strong>Subjects: </strong>1168 men seeking medical help for primary couple's infertility at a single centre.</p><p><strong>Exposure: </strong>Patients underwent thorough assessments, including medical history, measured body mass index (BMI), laboratory investigations including semen analyses and Sperm DNA fragmentation (SDF) index testing.</p><p><strong>Main outcome measures: </strong>Abnormal SDF was defined when >30%. Descriptive statistics and logistic regression analyses tested the association between semen parameters, SDF and positive cancer family history.</p><p><strong>Results: </strong>Of 1168, 168 (14.4%) patients reported a positive cancer familial history. Patients with positive cancer family history were older [median (IQR): 37.00 (33.00, 41.00) vs. 38.00 (34.00, 41.00) years; p=0.036)] and more frequently smokers [271 (27.1) vs. 64 (38.1); p<0.001]. A positive family history for malignancies was observed in 79 (40.9%), 66 (34.2%), 36 (18.7%) and 6 (3.1%) patients with a 1<sup>st</sup>, 2<sup>nd</sup>, 3<sup>rd</sup> and 4<sup>th</sup> 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; p=0.048) and in 1<sup>st</sup>-degree relatives (HR:1.01; 95% CI:1.00 - 1.03; p=0.050). 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; p=0.043) and in 1<sup>st</sup>-degree relatives (HR:1.92; 95% CI:1.01- 3.84; p=0.049).</p><p><strong>Conclusions: </strong>Almost 14% of MFI patients 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":"2025-03-21","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}
F&S sciencePub Date : 2025-03-19DOI: 10.1016/j.xfss.2025.03.001
Keelee J McCarty, Blair McCallie, William B Schoolcraft, Mandy Katz-Jaffe
{"title":"Utilization of a 3D 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":"https://doi.org/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 utilize a novel, time-lapse 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). Following 72h 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 Intervention (for RCT) or Exposure (for observational studies): N/A MAIN OUTCOME MEASURES: Immunohistochemistry and targeted qPCR gene expression were performed on individual blastocysts and on exosome purified small RNAs derived from supernatant.</p><p><strong>Results: </strong>Following 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 to slower developing blastocysts. Additionally, targeted gene expression analysis revealed an upward trend of implantation promoting genes GATA3, OCT4, and cell death regulatory gene CASP3 in correctly timed compared to slower developing blastocysts. Interestingly, as blastocysts became more attached to the epithelium, a downward trend of developmental genes CDX2 and BMP15 was observed. A downward trend of hsa-miR-1-3p and upward trend of hsa-miR-34b-5p was observed in the supernatant of co-cultured blastocysts that achieved successful implantation in co-culture. Top KEGG pathways impacted by these microRNA's 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}
F&S sciencePub Date : 2025-02-27DOI: 10.1016/j.xfss.2025.01.005
Allison S Komorowski, John S Coon V, Melania Anton, Azna Zuberi, Olivia Sotos, Serdar E Bulun, Ping Yin
{"title":"Stearoyl-coenzyme A desaturase enhances cell survival in human uterine leiomyoma.","authors":"Allison S Komorowski, John S Coon V, Melania Anton, Azna Zuberi, Olivia Sotos, Serdar E Bulun, Ping Yin","doi":"10.1016/j.xfss.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.01.005","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>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 MED12 mutant human uterine smooth muscle (UtSM) cell line, were treated with SCD1 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.</p><p><strong>Subjects: </strong>Leiomyoma and myometrial tissues were obtained from premenopausal individuals designated female at birth (n = 30) undergoing myomectomy or hysterectomy.</p><p><strong>Exposures: </strong>SCD1 inhibition by small interfering RNA and CAY10566 treatment.</p><p><strong>Main outcome measures: </strong>Messenger RNA (mRNA) and protein levels and cell viability and apoptosis.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","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}
F&S sciencePub Date : 2025-02-25DOI: 10.1016/j.xfss.2025.02.007
Pamela B Parker, Melinda J Murphy, Sweta Ravisankar, Shawn L Chavez, Jon D Hennebold
{"title":"Impact of a short-term Western-style diet and hyperandrogenism on adult rhesus macaque ovarian function.","authors":"Pamela B Parker, Melinda J Murphy, Sweta Ravisankar, Shawn L Chavez, Jon D Hennebold","doi":"10.1016/j.xfss.2025.02.007","DOIUrl":"10.1016/j.xfss.2025.02.007","url":null,"abstract":"<p><strong>Objective: </strong>To determine the effect of an obesogenic Western-style diet and hyperandrogenemia on ovarian outcomes.</p><p><strong>Design: </strong>Experimental, controlled animal study.</p><p><strong>Subjects: </strong>Post-pubertal rhesus macaque females.</p><p><strong>Exposure: </strong>A Western-style diet (WSD) (WSD: 36% fat, 45% carbohydrate, 18% protein) combined with exogenously administered testosterone (T) vs. a standard chow diet (control; 15% fat, 59% carbohydrate, 27% protein). Animals underwent controlled ovarian stimulations to assess ovarian follicle development.</p><p><strong>Main outcome measures: </strong>Cycle length, the proportion of ovulatory cycles, and daily levels of estradiol (E2), progesterone, antimüllerian hormone, luteinizing hormone, and follicle-stimulating hormone were compared between control and T+WSD groups through one menstrual cycle. Follicular fluid was assessed for cytokine and steroid content, and retrieved oocytes were evaluated for meiotic maturation and underwent in vitro fertilization. Granulosa cells were analyzed for differential gene expression. Ovaries were removed in early luteal phase (4 days post midcycle estradiol surge) and analyzed for morphological differences.</p><p><strong>Results: </strong>The T+WSD group demonstrated significantly decreased luteal progesterone levels. We found no differences in cycle length, proportion of ovulatory cycles, day of E2 surge, total E2 synthesis, follicle-stimulating hormone, luteinizing hormone or antimüllerian hormone. Analysis of follicular fluid retrieved from animals undergoing an ovarian stimulation protocol revealed increased vascular endothelial growth factor-A, elevated cortisol:cortisone ratio, and increased testosterone and progesterone levels in the treatment group. Granulosa cells from T+WSD demonstrated significantly up-regulated or down-regulated genes relative to controls, including those related to cell differentiation and migration. The ovarian morphology of treatment animals demonstrated enlarged cystic follicles reminiscent of polycystic ovaries.</p><p><strong>Conclusion: </strong>Similar to prior studies assessing long-term exposure (5-6 years) to T+WSD in female rhesus macaques beginning before menarche, a 1-year T+WSD treatment in adult, regularly cycling females led to reduced luteal phase progesterone levels and polycystic ovarian morphology. Additionally, short-term T+WSD exposure resulted in altered granulosa cell gene expression. Although 1 year of T+WSD exposure leads to altered luteal progesterone, follicular fluid steroid and cytokine content, and granulosa cell gene expression changes, insults of longer duration are required to exert additional negative effects on ovarian function.</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":"143525341","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}