F&S science最新文献

{"title":"Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway","authors":"Adina Schwartz M.D. ,&nbsp;Minnie Malik Ph.D. ,&nbsp;Paul Driggers Ph.D. ,&nbsp;William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2024.12.004","DOIUrl":"10.1016/j.xfss.2024.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>To determine if the oral gonadotropin-releasing hormone antagonist relugolix affects leiomyoma extracellular matrix production through the transforming growth factor-beta (TGF-β) pathway.</div></div><div><h3>Design</h3><div>Laboratory study.</div></div><div><h3>Subjects</h3><div>None.</div></div><div><h3>Exposure</h3><div>Exposure of human leiomyoma cells to TGF-β and/or relugolix.</div></div><div><h3>Main Outcome Measures</h3><div>Production of TGF-β, pSMAD2/3, SMAD2/3, collagen 1A1 (COL1A1), fibronectin (FN1), and versican (VCAN) in treated and untreated leiomyoma cells.</div></div><div><h3>Results</h3><div>Transforming growth factor-beta 3 production decreased at 24 hours with relugolix 10 nM (0.80 ± 0.09-fold) and 100 nM (0.86 ± 0.06-fold) and at 48 hours with relugolix 1 nM (0.86 ± 0.05-fold) and 100 nM (0.86 ± 0.06-fold). pSMAD2/3 production decreased at 24 hours with relugolix 1 nM (0.71 ± 0.01-fold), 10 nM (0.68 ± 0.01-fold), and 100 nM (0.41 ± 0.10-fold). Compared with relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 1 nM, 10 nM, and 100 nM. At 48 hours, combination treatment resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 10 nM and 100 nM.</div></div><div><h3>Conclusion</h3><div>Relugolix regulated leiomyoma size by decreasing COL1A1, FN1, and VCAN production. This effect is at least partly through the TGF-β pathway.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 213-220"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904284","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":"Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos","authors":"Gilad Karavani M.D. ,&nbsp;Shira Shapira-Nass M.D. ,&nbsp;Natali Schachter-Safrai M.D. ,&nbsp;Tal Imbar M.D. ,&nbsp;Assaf Ben-Meir M.D.","doi":"10.1016/j.xfss.2025.01.003","DOIUrl":"10.1016/j.xfss.2025.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the association between polycystic ovary syndrome (PCOS) and the rate of embryo development, using time-lapse monitoring systems, compared with a control group of women with mechanical (tubal) factor infertility.</div></div><div><h3>Design</h3><div>A retrospective case-control study conducted in a university-affiliated in vitro fertilization (IVF) unit.</div></div><div><h3>Subjects</h3><div>Women with PCOS undergoing IVF treatments and those with non-PCOS controls with tubal factor infertility only. Development morphokinetic milestones were compared and analysis of covariance for time to distinct cell number as well as logistic mixed models to determine predictors for embryos over the 75th percentile was performed.</div></div><div><h3>Exposure</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measures</h3><div>Embryo development morphokinetic parameters in women with and without PCOS undergoing IVF treatments.</div></div><div><h3>Results</h3><div>The study included 791 embryos from 115 women, 364 embryos from 52 women with PCOS and 427 embryos from 63 women with non-PCOS controls with tubal factor infertility. The PCOS group was 4 years younger (30.07 ± 6.03 vs. 34.08 ± 4.84 years) and had higher number of oocytes retrieved (16.00 vs. 11.00), mature oocytes (11.00 vs. 7.00) and fertilized oocytes (8.00 vs. 5.00). The PCOS and control groups demonstrated comparable clinical pregnancy rates (55.8% vs. 32.1%), miscarriage rate (12.5% vs. 11.8%), and live birth rate (48.8% vs. 31.2%). Morphokinetic parameters were comparable between the groups. Although age was associated with later time to 5 and 8 discrete cells and start of blastulation (tSB), PCOS was only associated with later tSB, including tSB &gt;75th percentile.</div></div><div><h3>Conclusion</h3><div>This study demonstrated comparable IVF outcomes in women with PCOS and non-PCOS controls. An analysis of time-lapse monitoring data from these patients showed no evidence that PCOS negatively affects embryonic development rate in women undergoing IVF cycles.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 252-260"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017331","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":"Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation","authors":"Nirukshi Samarajeewa Ph.D. ,&nbsp;Sophea Heng Ph.D. ,&nbsp;Ying Li B.Eng. ,&nbsp;Maxine Scelwyn M.D. ,&nbsp;Luk J. Rombauts M.D. Ph.D. ,&nbsp;Guiying Nie Ph.D.","doi":"10.1016/j.xfss.2024.11.002","DOIUrl":"10.1016/j.xfss.2024.11.002","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether endometrial receptivity is affected in patients with endometriosis using podocalyxin (PCX) as a functional biomarker and to study how endometriotic lesions display PCX and the potential pathological implications.</div></div><div><h3>Design</h3><div>We have previously reported that PCX, an anti-adhesion glycoprotein and barrier protector, is dynamically regulated in the endometrium and acts as a key negative regulator of epithelial receptivity. Early in the cycle both luminal epithelium (LE, lining the endometrial surface) and glandular epithelium (GE, residing within the tissue) strongly express PCX, but in the receptive window, PCX is selectively downregulated in LE, switching the endometrial surface to an adhesive state for embryo attachment/implantation; meanwhile, PCX expression is maintained in GE until postreceptivity. Here, we immuno-stained PCX in endometrial tissues and ectopic lesions biopsied across the menstrual cycle from patients with endometriosis (EOS, n = 41), and compared with endometrium of non-endometriosis controls (non-EOS, n = 55). We further investigated how PCX changes observed in ectopic lesions may influence their adhesive capacity.</div></div><div><h3>Subjects</h3><div>Women without and with endometriosis.</div></div><div><h3>Exposure</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measures</h3><div>The window of endometrial receptivity might be shorter in patients with endometriosis; ectopic sites in addition downregulate PCX cyclically, mirroring the eutopic endometrial cells in preparing for receptivity to increase their adhesion potential.</div></div><div><h3>Results</h3><div>Endometrial PCX levels were comparable between non-EOS and EOS early in the cycle, and in both groups, PCX is downregulated in LE during the expected window of receptivity; however, in EOS endometrium, PCX is reduced earlier in GE as if the receptive window were shorter. In endometriotic lesions, PCX was detected in endometrial LE- and GE-like cells plus mesothelial cells enveloping peritoneal organs, but PCX was cyclically lost specifically in LE-like cells and reduced in GE-like cells as seen in the eutopic endometrium, which however may increase their adhesion potential to nearby organs (overlaid by mesothelial cells). This speculation was further corroborated in an in vitro model showing endometrial epithelial cells with lower PCX were indeed more adhesive to mesothelial cells.</div></div><div><h3>Conclusion</h3><div>Endometrial receptivity is subtly affected in patients with endometriosis with a shorter window. Cyclic downregulation of PCX in ectopic sites may have pathological consequences.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 232-241"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792887","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":"Chemotherapy-induced diminished murine ovarian reserve model and impact of low-dose chemotherapy on fertility","authors":"Lara Houeis M.D. ,&nbsp;Graziella van der Plancke B.Sc. ,&nbsp;Jen-Yu Wen M.D. ,&nbsp;Laurence Dupuy Ph.D. ,&nbsp;Elodie Kara Ph.D. ,&nbsp;Luciana Cacciottola M.D., Ph.D. ,&nbsp;Marie-Christine Maurel Ph.D. ,&nbsp;Jacques Donnez M.D., Ph.D. ,&nbsp;Marie-Madeleine Dolmans M.D., Ph.D.","doi":"10.1016/j.xfss.2025.01.002","DOIUrl":"10.1016/j.xfss.2025.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>To establish a murine model of chemotherapy-induced diminished ovarian reserve (DOR) and investigate residual fertility after chemotherapy exposure.</div></div><div><h3>Design</h3><div>Two different chemotherapy protocols were tested to establish a valid DOR model by comparing follicle densities in mice given either protocol or physiological solution. An ovarian stimulation protocol was then selected from among different gonadotropins by counting the number of day 2 embryos obtained from normal mice. Finally, DOR mice were stimulated 5 and 8 weeks after chemotherapy with the chosen gonadotropin protocols, and day 2 embryos were recovered after mating, as was ovarian tissue for further immunohistologic analyses.</div></div><div><h3>Subjects</h3><div>Seventy-two Naval Medical Research Institute mice.</div></div><div><h3>Exposure</h3><div>Two different chemotherapy protocols.</div></div><div><h3>Main Outcome Measures</h3><div>This study compared day 2 embryo counts in both normal and chemotherapy-induced DOR mice. Ovarian histology and morphology were also investigated by follicle counting and classification, as was immunostaining for apoptosis (cleaved caspase-3), activation (phospho-Akt), and proliferation (Ki67).</div></div><div><h3>Results</h3><div>A dose of 12 mg/kg of busulfan (Bu) + 120 mg/kg of cyclophosphamide (Cy) was chosen to establish the DOR model as it significantly reduced the ovarian reserve compared to both control mice (physiological solution) and the 1.2 mg/kg of Bu + 12 mg/kg of Cy protocol, without depleting it completely. When stimulated with 3.75 IU of Menopur, normal mice produced significantly more embryos than DOR mice given 12 mg/kg of Bu + 120 mg/kg of Cy (41.40 ± 14.74 vs. 23.67 ± 15.55 day 2 embryos). Although the follicle count was statistically diminished after single-dose chemotherapy administration, the remaining follicles did not display any difference in terms of apoptosis, activation, or proliferation rates.</div></div><div><h3>Conclusion</h3><div>We successfully established a chemotherapy-induced DOR model using 12 mg/kg of Bu + 120 mg/kg of Cy, as evidenced by lower, but not completely depleted, follicle numbers and fewer retrieved embryos. Histologic study of ovarian tissue exposed to DOR-inducing chemotherapy revealed that surviving follicles were of the similar quality as tissue not exposed to chemotherapy.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 177-185"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973627","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":"Feasibility study of the application of magnetic resonance elastography to diagnose uterine adenomyosis","authors":"Varsha Jain Ph.D. ,&nbsp;Emi Hojo M.Sc. ,&nbsp;Graham McKillop M.B.Ch.B. ,&nbsp;Anca Oniscu M.D. ,&nbsp;Yuan Le Ph.D. ,&nbsp;Jun Chen Ph.D. ,&nbsp;Richard Ehman Ph.D. ,&nbsp;Neil Roberts Ph.D. ,&nbsp;Hilary O.D. Critchley M.D., D.Sc.","doi":"10.1016/j.xfss.2025.03.003","DOIUrl":"10.1016/j.xfss.2025.03.003","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>A feasibility study in which a 3-dimensional (3D) MRE imaging protocol was developed to measure the stiffness of the tissues of the uterus.</div></div><div><h3>Subjects</h3><div>Four patients with suspected adenomyosis and heavy menstrual bleeding diagnosed via transvaginal ultrasound and clinical history and 1 healthy control were recruited. Two patients underwent hysterectomy, and histologic analysis of the tissue samples was performed.</div></div><div><h3>Main Outcome Measures</h3><div>The stiffness of the whole uterus was obtained by region of interest analysis of the 3D MRE images for the 4 patients and 1 healthy control. In addition, for the 2 patients who underwent hysterectomy, the uterine tissue samples were assessed to determine histologic presence of adenomyosis via hematoxylin and eosin staining, cellular/molecular measures of tissue stiffness (collagen [picrosirius red], α-smooth muscle actin, and e-cadherin), and whether a relationship existed between in vivo assessment of the uterus via 3D MRE and in vitro uterine tissue histology.</div></div><div><h3>Results</h3><div>3D MRE was successfully used to acquire elastograms for 4 patients with adenomyosis (diffuse, n = 3; focal, n = 1) and 1 healthy control. Calculated global uterine stiffness was higher in women with adenomyosis (2.93 kPa; range, 2.34–3.39 kPa) than in the healthy control (2.04 kPa). Regions of high stiffness on the 3D elastograms reflected adenomyotic changes visualized via conventional magnetic resonance imaging and were correlated with histologic and immunohistochemical markers of tissue stiffness.</div></div><div><h3>Conclusion</h3><div>3D MRE has the potential to provide non-invasive characterization of changes in the mechanical properties of uterine tissue that is not possible using conventional magnetic resonance imaging or transvaginal ultrasound. Further studies are needed to confirm the efficacy of the 3D MRE protocol for diagnosing adenomyosis.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 242-251"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}

{"title":"Effect of endometriosis-linked microRNAs on hepatic gene expression","authors":"Ramanaiah Mamillapalli Ph.D.,&nbsp;Rebecca Slutzky B.A.,&nbsp;Anjali Mangla B.A.,&nbsp;Nimisha Gawde M.D.,&nbsp;Hugh S. Taylor M.D.","doi":"10.1016/j.xfss.2025.02.001","DOIUrl":"10.1016/j.xfss.2025.02.001","url":null,"abstract":"<div><h3>Objective</h3><div>To determine if microRNAs that are altered in the circulation of women with endometriosis affect metabolic gene expression in hepatic cells.</div></div><div><h3>Design</h3><div>In vitro study.</div></div><div><h3>Subjects</h3><div>Deidentified tissue from women with endometriosis.</div></div><div><h3>Exposure</h3><div>MicroRNAs were used to induce or suppress target genes in hepatic cells.</div></div><div><h3>Main Outcome Measures</h3><div>Effect of the microRNAs that are aberrantly expressed in endometriosis on hepatic cell gene expression using quantitative polymerase chain reaction.</div></div><div><h3>Results</h3><div>Prior microarray studies on the serum of women with endometriosis showed differential expression of microRNAs miR-Let-7b, miR-125b-5p, miR-150-5p, and miR-3613-5p. Bioinformatic analyses revealed that these microRNAs have predicted binding sites in multiple genes involved in liver metabolism. Transfection of these miRs in HepG2 cells followed by real-time quantitative polymerase chain reaction showed that miR-Let-7b mimic increased the expression of <em>Igfbp1</em> by 8-fold and reduced the expression of <em>Mrc1</em> by 3.2-fold, whereas its inhibitor reduced <em>Igfbp1</em> by 2.8-fold and increased <em>Mrc1</em> by 5.2-fold. MiR-3613-5p mimic reduced the expression of <em>Cyp2r1</em> by 2.2-fold and <em>Mrc1</em> by 4-fold. MiR-125b-5p mimic increased the expression of <em>Fabp4</em> by 4.1-fold, whereas miR-150-5p mimic increased the expression of <em>Mrc1</em> by 1.8-fold and <em>Cyp2r1</em> by 2.5-fold. Inhibitors of both miR-125b-5p and miR-150-5p did not show any effect on any of the genes.</div></div><div><h3>Conclusion</h3><div>Circulating microRNAs, known to be aberrant in endometriosis-regulated hepatic gene expression, likely contribute to the metabolic defects seen in this disease. Treatment with miR-Let-7b and miR-3613-5p, which are downregulated in endometriosis, reversed the effect of endometriosis on the expression of <em>IGFBP1</em>, <em>MRC1,</em> and <em>CYP2r1</em> genes. Therefore, miR-Let-7b and miR-3613-5p may be novel candidate therapies for endometriosis, potentially correcting the metabolic changes seen in patients with endometriosis.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 221-231"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461057","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":"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}