F&S science最新文献

{"title":"Impact of a short-term Western-style diet and hyperandrogenism on adult rhesus macaque ovarian function","authors":"Pamela B. Parker M.D., M.P.H. ,&nbsp;Melinda J. Murphy B.S. ,&nbsp;Sweta Ravisankar Ph.D. ,&nbsp;Shawn L. Chavez Ph.D. ,&nbsp;Jon D. Hennebold Ph.D.","doi":"10.1016/j.xfss.2025.02.007","DOIUrl":"10.1016/j.xfss.2025.02.007","url":null,"abstract":"<div><h3>Objective</h3><div>To determine the effect of an obesogenic Western-style diet and hyperandrogenemia on ovarian outcomes.</div></div><div><h3>Design</h3><div>Experimental, controlled animal study.</div></div><div><h3>Subjects</h3><div>Post-pubertal rhesus macaque females.</div></div><div><h3>Exposure</h3><div>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.</div></div><div><h3>Main Outcome Measures</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 141-151"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}

{"title":"Kinetics of cell shrinkage and developmental competence of mouse zygotes vitrified following conventional or automated (DaVitri) protocols","authors":"Javier Guerrero-Sánchez Ms.C. ,&nbsp;Andrea Fernández-Toribio Ms.C. ,&nbsp;Beatriz Galiano-Cogolludo Ms.C. ,&nbsp;Tania García-Martínez Ph.D. ,&nbsp;Lucía Mendoza Ph.D. ,&nbsp;Gonzalo Fernández-Blanco Ms.C. ,&nbsp;Jesús Ramos-Membrive Ms.C. ,&nbsp;Joana Fidalgo Ph.D. ,&nbsp;Lionel Matthys Ms.C. ,&nbsp;José Antonio Horcajadas Ph.D. ,&nbsp;Santiago Munné Ph.D. ,&nbsp;Pablo Bermejo-Álvarez D.V.M., Ph.D.","doi":"10.1016/j.xfss.2025.03.006","DOIUrl":"10.1016/j.xfss.2025.03.006","url":null,"abstract":"<div><h3>Objective</h3><div>To test the developmental ability of murine zygotes vitrified using a novel vitrification device and microfluidic chip (DaVitri, Overture Life).</div></div><div><h3>Design</h3><div>Murine zygotes were randomly allocated to 2 groups; one was vitrified using the vitrification device, and the other was following a conventional manual protocol.</div></div><div><h3>Subjects</h3><div>Murine zygotes obtained in vivo.</div></div><div><h3>Exposure</h3><div>Automatic vitrification was achieved by a linear exposure to cryoprotectants (CPAs) using the DaVitri device. Manual vitrification was conducted using Kitazato kit.</div></div><div><h3>Main Outcome Measures</h3><div>Morphokinetic behavior of the zygotes during the exposure to CPAs analyzed by microscopy, developmental rates after thawing, lineage development at the blastocyst stage assessed by immunohistochemistry and light-structured fluorescent microscopy, and survival rates and pup weight after embryo transfer.</div></div><div><h3>Results</h3><div>Automated vitrification led to a gradual reduction in zygote volume during the equilibration steps preceding ultrafast 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 CPAs. 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 186-194"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}

{"title":"Enhanced ovarian FKBP51 expression is associated with ovarian aging: a molecular insight for age-related fertility in women","authors":"Papri Sarkar M.D. ,&nbsp;Monica Moore M.Sc ,&nbsp;Asli Ozmen PhD ,&nbsp;Busra Cetinkaya-Un Ph.D ,&nbsp;Vitko Julie M.D. ,&nbsp;Anthony N. Imudia M.D ,&nbsp;Charles J. Lockwood M.D. ,&nbsp;Umit A. Kayisli Ph.D. ,&nbsp;Ozlem Guzeloglu-Kayisli Ph.D.","doi":"10.1016/j.xfss.2025.01.004","DOIUrl":"10.1016/j.xfss.2025.01.004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To study the relationship between FK506-binding protein 51 (FKBP51) and ovarian aging and/or diminished ovarian reserve (DOR) in human ovaries by comparing FKBP51 levels in granulosa cells (GCs) and cumulus cells (CCs), collected during controlled ovarian stimulation (COS) from women of advanced reproductive age and/or with a diagnosis of DOR with that of young women with normal ovarian reserve. To explore the association between increased FKBP51 expression and human ovarian aging further, expression of FKBP51 was compared in ovarian stroma of postmenopausal vs. premenopausal women. Lastly, this relation was further queried by comparing ovarian expression of several collagen genes as markers of ovarian fibrosis in 14-month-old wild-type (&lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;+/+&lt;/em&gt;&lt;/sup&gt;) and &lt;em&gt;Fkbp5&lt;/em&gt; knockout (&lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt;) mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Laboratory-based experimental study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Samples collected included follicular fluid, CCs, GCs, and serum from group 1: young women with normal ovarian reserve (&lt;35 years; n = 12); group 2: DOR (antimüllerian hormone &lt;1 ng/mL; n = 10); and group 3: women of advanced age with normal ovarian reserve (&gt;37 years; n = 8). Ovarian stromal tissues obtained from surgical specimen of post-menopausal (50–65 years; n = 6) and pre-menopausal (18–30 years; n = 6). Ovarian tissues from 14-month-old &lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;+/+&lt;/em&gt;&lt;/sup&gt; &lt;em&gt;and Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; mice. All the experiments were performed at an academic-affiliated assisted reproductive technology unit/laboratory.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;Comparison of FKBP51 expression in GCs and CCs from women undergoing COS, ovarian stromal tissue from pre- and post-menopausal women, and ovarian tissue from aged &lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;+/+&lt;/em&gt;&lt;/sup&gt; &lt;em&gt;and Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;(1) Level of FKBP51 in human GCs and CCs, collected during COS by performing real-time quantitative polymerase chain reaction (qPCR). (2) Immunohistochemistry to detect FKBP51 levels and Picrosirius Red staining to detect collagen deposition in human ovarian stromal tissue. (3) Real-time qPCR to compare expression levels of several collagen genes in &lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;+/+&lt;/em&gt;&lt;/sup&gt; and &lt;em&gt;Fkbp5&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; old mice ovaries. Serum and follicular fluid levels of transforming growth factor β1, and soluble endoglin measured by enzyme-linked immunosorbent assay.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Immunohistochemistry revealed that FKBP51 histologic score levels in ovarian stromal tissue were significantly higher in postmenopausal vs. premenopausal women (mean ± SEM, 160.52 ± 17.75 vs. 120.67 ± 14.33; &lt;em&gt;P&lt;/em&gt;=.002). Stronger Picrosirius Red staining, suggestive of fibrosis, was seen in ovarian stromal tissue of postmenopausal vs. premenopausal women (54.06 ± 6.94 vs. 37.5","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 152-163"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017305","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}

{"title":"Genetic insights into the immunological basis of male infertility: a translational perspective","authors":"Yi Wang M.D. ,&nbsp;Yanggang Hong M.D.","doi":"10.1016/j.xfss.2025.02.002","DOIUrl":"10.1016/j.xfss.2025.02.002","url":null,"abstract":"<div><h3>Objective</h3><div>To elaborate the causal relationships between specific immunocyte phenotypes and male infertility.</div></div><div><h3>Design</h3><div>Mendelian randomization using genome-wide association study data.</div></div><div><h3>Subjects</h3><div>Large cohorts of European ancestry.</div></div><div><h3>Exposure</h3><div>731 immunocyte phenotypes or male infertility.</div></div><div><h3>Main Outcomes Measures</h3><div>Genetic variants were used as instrumental variables to infer causality, minimizing confounding and bias. The causal associations were assessed using the inverse variance-weighted (IVW) method for primary analysis, and the findings were validated using MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Additional sensitivity analyses were performed to validate the robustness of the findings.</div></div><div><h3>Results</h3><div>Our analysis identified significant causal associations between specific immunocyte phenotypes and male infertility. Phenotypes such as naive-mature B cell %lymphocyte (odds ratio [OR] = 1.257) and IgD− CD38dim %B cell (OR = 1.100) were positively associated with increased infertility risk, whereas phenotypes like CD39+ CD8br %T cell (OR = 0.856) and B cells activator of the TNF-α family receptor (BAFF-R) on transitional (OR = 0.833) were negatively associated, suggesting a protective effect. Additionally, reverse MR analysis revealed that male infertility might causally affect certain immunocyte phenotypes, including CD14- CD16+ monocyte %monocyte (OR = 1.049).</div></div><div><h3>Conclusion</h3><div>This study provides robust evidence for the causal role of specific immunocyte phenotypes in male infertility and highlights the bidirectional relationship between immune function and reproductive health. These findings provide new insights into the immunological factors contributing to male infertility and suggest potential biomarkers and therapeutic targets for future research and clinical interventions.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 130-140"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484940","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}

{"title":"Prioritization of potential drug targets in ovarian-related diseases: Mendelian randomization and colocalization analyses","authors":"Yanggang Hong M.D.","doi":"10.1016/j.xfss.2025.02.003","DOIUrl":"10.1016/j.xfss.2025.02.003","url":null,"abstract":"<div><h3>Objective</h3><div>To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses.</div></div><div><h3>Design</h3><div>We conducted a comprehensive two-sample MR analysis to estimate the causal effects of blood expression quantitative trait loci (eQTLs) on ovarian-related diseases, followed by colocalization analyses to verify the robustness of the expression instrumental variables (IVs). Phenome-wide association studies (PheWAS) were also performed to evaluate the horizontal pleiotropy of potential drug targets and possible side effects.</div></div><div><h3>Subjects</h3><div>Large cohorts of European ancestry.</div></div><div><h3>Exposure</h3><div>The exposure in this study was the genetic variants (eQTLs) associated with gene expression levels, considered a form of lifelong exposure. Expression quantitative trait loci data were obtained from the eQTLGen Consortium, encompassing 16,987 genes and 31,684 cis-eQTLs derived from blood samples of healthy individuals of European ancestry.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome measures were the identification of genes causally associated with ovarian-related diseases and the validation of these genes as potential therapeutic targets.</div></div><div><h3>Results</h3><div>Our study revealed that specific genes such as CD163L1, PPP3CA, MTAP, F12, NRM, BANK1, ZNF66, GNA15, and SLC6A9 were associated with ovarian endometriosis, ovarian cysts, and polycystic ovarian syndrome. Through MR and colocalization analyses, we identified potential drug targets, including CTNNB1, PTPN7, and ABCB4, with strong evidence of colocalization with ovarian-related diseases. Sensitivity analyses confirmed the robustness of our findings, showing no evidence of horizontal pleiotropy or heterogeneity.</div></div><div><h3>Conclusion</h3><div>This research highlights the significance of precision medicine approaches in identifying genetic factors underlying ovarian-related diseases and provides a foundation for developing targeted therapies, enhancing diagnostic accuracy, and improving treatment strategies for ovarian-related diseases.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 164-176"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484944","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}

{"title":"Corrigendum to “From the Editor-in-Chief” (F S Sci 2025;6:1–3)","authors":"","doi":"10.1016/j.xfss.2025.02.005","DOIUrl":"10.1016/j.xfss.2025.02.005","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Page 261"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}

{"title":"From the Editor-in-Chief","authors":"William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2025.04.001","DOIUrl":"10.1016/j.xfss.2025.04.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Page 117"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}

{"title":"Direct assessment of hereditary hemochromatosis in preimplantation genetic testing","authors":"Qinnan Zhang Ph.D.,&nbsp;Maria Katz M.Sc.,&nbsp;Benjamin Podgursky M.Sc.,&nbsp;Nicholas Schuch B.S.,&nbsp;Shenglai Li M.Sc.,&nbsp;Noor Siddiqui M.Sc.,&nbsp;Funda Suer Ph.D.,&nbsp;Yuntao Xia Ph.D.","doi":"10.1016/j.xfss.2024.12.003","DOIUrl":"10.1016/j.xfss.2024.12.003","url":null,"abstract":"<div><h3>Objective</h3><div>Hereditary hemochromatosis (HH) is a common genetic disorder characterized by iron overload, which, if undiagnosed, can lead to severe organ damage. There are 4 types of HH. Type 1 HH, the most common form, is primarily caused by a common variant in Western Europe (p.Cys282Tyr, C282Y, or c.845 G&gt;A). It is generally preventable during in vitro fertilization if proper genetic testing is performed before implantation. Here, we demonstrated a direct detection and cost-effective approach using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in preimplantation genetic testing (PGT) settings.</div></div><div><h3>Design</h3><div>We began by validating the assay with genomic deoxyribonucleic acid (DNA) from Coriell cell lines of known HFE C282Y genotypes, followed by testing patients’ genomic DNA samples. After establishing the assay on genomic DNA, we extended the assay to whole-genome amplified DNA from embryo biopsies.</div></div><div><h3>Subjects</h3><div>The subjects include cell line samples and human specimens and human embryo biopsies.</div></div><div><h3>Exposure</h3><div>Patients and embryos either carried or did not carry the HFE C282Y variant in their genome. No intervention was applied.</div></div><div><h3>Main Outcome Measures</h3><div>The readout included the genotype of samples at the HFE C282Y locus and accuracy of PCR-RFLP results.</div></div><div><h3>Results</h3><div>An accuracy of &gt;99% was achieved across 80 cell line samples, 38 patient samples, and 81 embryo biopsies.</div></div><div><h3>Conclusion</h3><div>In this study, we demonstrated the feasibility of using the PCR-RFLP approach to PGT. Specifically, we validated the assay for the HFE C282Y variant, the primary cause of type 1 hemochromatosis. The assay was tested on genomic DNA and DNA resulting from whole-genome amplification, achieving &gt;99% accuracy, sensitivity, precision, and specificity. These results also suggest the possibility for extending the PCR-RFLP approach to cover a broader range of conditions, such as spinal muscular atrophy, to benefit more patients currently ineligible for testing at PGT laboratories.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 195-201"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883745","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}

{"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}

{"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}