F&S science最新文献

{"title":"The Dual Role of IL-22: Balancing Protection and Risk in Pregnancy during Inflammatory Challenges.","authors":"Umida Ganieva, Mahmood Bilal, Ana Adam, Cecilia Pena-Rasgado, Wren Michaels, Hector Rasgado-Flores, Amy Thees, Thanh Luu, Joanne Kwak-Kim, Svetlana Dambaeva","doi":"10.1016/j.xfss.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.09.001","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the potential of recombinant IL-22 (rIL-22) in preventing inflammation-triggered abortion.</p><p><strong>Design: </strong>Using wild type (WT, C57BL/6J) and IL-22 knock out (IL-22^-/-) mice aged 7-14 weeks, we induced abortion via intraperitoneal injection of lipopolysaccharide (LPS) on gestational day (GD) 8.5, mimicking inflammatory challenges encountered during mid-gestational pregnancy. Prior to LPS administration, mice were treated with varying doses of rIL-22 via tail vein injection. Uterine tissue was harvested 48 hours post-LPS injection (n=6/group), or mice were monitored until delivery (GD 20.5) (n=3/group). Transepithelial electric resistance assessed transport integrity of tight junction in uterine epithelial cell culture. Gene expression levels were quantified using qRT-PCR, while immunohistochemistry/immunofluorescence evaluated tissue distribution of relevant antigens. Multiplex-based immunoassay analysis was used to measure immune markers in the amniotic fluid.</p><p><strong>Results: </strong>Administration of rIL-22 to IL-22^-/- mice not only restored the endometrial mucosal architecture to levels similar to those of WT animals but also prevented abortion in a dose-dependent manner. While rIL-22 treatment rescued pregnancy in IL-22^-/- mice at doses of 5, 10, and 20 μg/mouse, only the lower doses (≤10 μg/mouse) were effective in WT mice. High dose (20 μg/mouse) of rIL-22, when followed by LPS injection, negatively affected pregnancy outcomes in WT mice, and the sole administration of 20 μg of rIL-22 resulted in adverse pregnancy outcomes in both genotypes.</p><p><strong>Conclusions: </strong>IL-22 emerges as a promising therapeutic target in reproductive medicine, offering potential avenues for preserving pregnancy in the face of inflammatory challenges. However, increased levels of IL-22 could be associated with reproductive failures, emphasizing the delicate balance required for immune regulation. Our study underscores the importance of immune regulation in reproductive health and highlights rIL-22 as a novel candidate for improving pregnancy outcomes in inflammatory conditions.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042420","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":"Transvaginal Shear Wave Elastography for Measuring Uterine Myometrial and Leiomyoma Stiffness: a Protocol Pilot Study.","authors":"Hannah T Ryles, Sumeyra Agambayev, Mervat Omran, Chuanhong Liao, Samar Alkhrait, Ayman Al-Hendy, Ryan Longman, Jacques Abramowicz, Obianuju Sandra Madueke-Laveaux","doi":"10.1016/j.xfss.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.xfss.2025.09.002","url":null,"abstract":"<p><strong>Objective: </strong>Recent studies suggest that the stiffness of uterine leiomyomas may be related to their growth and behavior. Shear wave elastography, a quantitative method of measuring tissue stiffness, has been increasingly studied for use in gynecologic conditions. However, no protocols have been proposed for its use in this clinical setting. This study aimed to 1) establish a standardized protocol for transvaginal shear wave elastography to measure uterine myometrial and leiomyoma stiffness and 2) assess the reproducibility and reliability of shear wave elastography measurements. We also assessed myometrial versus leiomyoma stiffness, compared myometrial stiffness in participants with and without leiomyomas, and assessed menstrual phase effects on stiffness values.</p><p><strong>Design: </strong>Transvaginal SWE ultrasound measurements of myometrial and leiomyoma stiffness were obtained. All transvaginal SWE exams were performed by an individual sonographer. Independent raters calculated stiffness measurements. Myometrial and leiomyoma stiffness were compared across menstrual phases.</p><p><strong>Subjects: </strong>Twenty-seven premenopausal women, 16 with leiomyomas and 11 without were enrolled. Seventeen participants completed exams during multiple menstrual phases.</p><p><strong>Exposure(s): </strong>1. Tissue type (Myometrium/Leiomyoma) 2. Leiomyoma status (Presence/Absence of leiomyomas) 3. Menstrual phase (Follicular/Luteal) MAIN OUTCOME MEASURES: Inter-rater and test-retest reliability of shear wave elastography measurements. Myometrial and leiomyoma shear wave values.</p><p><strong>Results: </strong>We successfully designed a streamlined protocol for obtaining shear wave elastography measurements in participants with and without leiomyomas. Fifty-one myometrial and 38 leiomyoma stiffness values measured by two independent raters achieved excellent inter-rater reliability: the intraclass correlation coefficients (ICC) between the two raters were 0.990 (p<0.001) and 0.994 (p<0.001), respectively. Fifty myometrial and 42 leiomyoma stiffness measurements calculated by a single rater at two time points at least 90 days apart, achieved excellent test-retest reliability: ICC=0.992, p<0.001; ICC=0.995, p<0.001. Median stiffness values for leiomyomas were significantly higher than the surrounding myometrium (48.1 (IQR 39.7-59.5) versus 31.6 (IQR 22.9-46.9) kPa, p<0.001). There was no significant change in myometrial or leiomyoma median stiffness values between the menstrual phases.</p><p><strong>Conclusion: </strong>Transvaginal ultrasound shear wave elastography showed excellent reproducibility and reliability in measuring myometrial and leiomyoma stiffness. Leiomyoma stiffness was significantly higher compared to the surrounding myometrium. Together, these findings support shear wave elastography's potential clinical utility in leiomyoma management.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042452","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":"Progesterone receptor isoform modulation via enhancer activation regulates progesterone signaling in endometrial stromal cells.","authors":"Skylar G Montague Redecke, Austin Bell-Hensley, MyeongJin Yi, Shuyun Li, Francesco J DeMayo","doi":"10.1016/j.xfss.2025.08.004","DOIUrl":"10.1016/j.xfss.2025.08.004","url":null,"abstract":"<p><strong>Objective: </strong>To investigate enhancer-mediated regulation of progesterone receptor (PGR) isoforms, PGR-A and PGR-B, in human endometrial stromal cells, and to determine how isoform modulation shapes the progesterone-responsive transcriptome and cistrome relevant to endometrial function.</p><p><strong>Design: </strong>A clustered regularly interspaced short palindromic repeats-based functional genomic screen was used to identify distal enhancers in telomerase-immortalized human endometrial stromal cells. Subsequent clustered regularly interspaced short palindromic repeats targeting of identified enhancers and the PGR promoter was used to modulate PGR isoform balance and assess functional consequences.</p><p><strong>Subjects: </strong>None.</p><p><strong>Exposure: </strong>Engineered endometrial stromal cells were treated with medroxyprogesterone acetate or vehicle.</p><p><strong>Main outcome measures: </strong>PGR isoform expression was assessed by western blot, the progesterone-responsive transcriptome was characterized by bulk ribonucleic acid sequencing, and the PGR cistrome was characterized by Cut&Run.</p><p><strong>Results: </strong>Two distal PGR enhancers were identified in endometrial stromal cells located approximately 60 and 220 kb upstream of the PGR transcription start site. Clustered regularly interspaced short palindromic repeats-based activation of these enhancers upregulated both PGR-A and PGR-B, whereas promoter activation primarily upregulated PGR-B. Bulk ribonucleic acid sequencing revealed that shifting the PGR isoform balance altered the progesterone-regulated transcriptome: PGR-A/B-equivalent cells exhibited proinflammatory gene signatures, whereas PGR-B-dominant cells demonstrated suppression of inflammatory signaling and altered cell cycle programs. The PGR Cut&Run profiling revealed distinct genomic binding patterns associated with each isoform profile. Integration of the PGR cistrome with chromatin interaction maps suggested that these isoforms directly regulate distinct gene subsets involved in inflammation and fibrosis. Mechanistically, estrogen receptor alpha (ESR1) indirectly activated PGR-A expression, potentially through recruitment of Forkhead box protein O1 (FOXO1) at the distal enhancer, suggesting a noncanonical, enhancer-mediated mechanism of PGR regulation.</p><p><strong>Conclusions: </strong>Distal enhancers regulate the PGR isoform balance and shape the progesterone-responsive transcriptome in human endometrial stromal cells. This enhancer-mediated mechanism expands current models of PGR regulation beyond promoter-level control and may offer potential therapeutic targets to restore normal progesterone responsiveness in conditions marked by PGR isoform imbalance.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of AMD3100 for bone marrow-derived mesenchymal stem cell mobilization in the treatment of murine Asherman's syndrome.","authors":"Valerie A Flores, Pablo A Delis, Ramanaiah Mamillapalli, Hugh S Taylor","doi":"10.1016/j.xfss.2025.08.003","DOIUrl":"10.1016/j.xfss.2025.08.003","url":null,"abstract":"<p><strong>Objective: </strong>Asherman syndrome (AS) is characterized by intrauterine adhesions/fibrosis, resulting from damage to the endometrial basalis layer. The consequences of AS include infertility, recurrent pregnancy loss, preterm rupture of membranes, and placental abruption. Hysteroscopic adhesiolysis does not consistently restore endometrial function; there is a need for more effective treatments. Bone marrow-derived mesenchymal stem cells (BMD-MSCs) circulate systemically and contribute to tissue repair/regeneration, suggesting that they may serve as a source of progenitor cells for endometrial regeneration. Increasing the supply of BMD-MSCs to the endometrium may treat AS by allowing for regeneration/replenishment of endometrial progenitor cells. Mobilization of autologous BMD-MSCs using AMD3100, a CXC-motif-receptor-4 antagonist, is approved for bone marrow transplantation. We aimed to determine whether the optimal timing of AMD3100 administration-on the basis of CXCL12 production-would better recruit BMD-MSCs in a murine model of severe AS and restore functioning endometrium/fertility.</p><p><strong>Design: </strong>Severe AS murine model.</p><p><strong>Subjects: </strong>C57BL/6 mice in the diestrus phase undergoing surgical AS induction.</p><p><strong>Exposure: </strong>Single injection with AMD3100 (treatment) or vehicle (saline). AMD3100 administration timing was based on the determination of maximum CXCL12 release after AS induction. Mice were then mated.</p><p><strong>Main outcome measures: </strong>Time to pregnancy, litter size, and miscarriage rate.</p><p><strong>Results: </strong>Maximum uterine CXCL12 production occurred 48 hours after AS induction; thus, AMD3100 vs. saline was administered 48 hours after induction. Of the AMD3100-treated mice, all achieved pregnancy and delivered. The treatment group became pregnant and delivered significantly sooner, indicating a faster time to conception (20 vs. 26 days). The treatment group had significantly larger litter sizes (6.5 vs. 4.2 pups) and significantly more live pups at delivery than the control group (6.0 vs. 2.7).</p><p><strong>Conclusion: </strong>AMD3100 had a significant effect on uterine repair and regeneration in AS. The likelihood of pregnancy was significantly higher and more rapid in AS mice treated with AMD3100. Treated mice also had larger litter sizes and fewer miscarriages than controls. Furthermore, we determined for the first time the levels of CXCL12 in uteri after uterine injury, which allowed for the determination of the optimal timing of AMD3100 administration, to ensure mobilized BMD-MSCs homed to the uterus.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862664","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":"Deciphering estrogen receptor alpha-driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape.","authors":"Skylar G Montague Redecke, Austin Bell-Hensley, Shuyun Li, MyeongJin Yi, Akshadha Jain, Abdull J Massri, Francesco J DeMayo","doi":"10.1016/j.xfss.2025.08.002","DOIUrl":"10.1016/j.xfss.2025.08.002","url":null,"abstract":"<p><strong>Objective: </strong>To investigate estrogen receptor gene 1 (ESR1) and estrogen-driven transcription in human endometrial stromal cells.</p><p><strong>Design: </strong>RNA sequencing (RNA-seq) and Cleavage Under Targets and Release Using Nuclease (Cut&Run) were performed on telomerase-immortalized human endometrial stromal cells with Clustered Regularly Interspaced Short Palindromic Repeats-mediated ESR1 activation. Hi-C-based chromatin architecture analysis (H3K27ac HiChIP) was conducted in primary endometrial stromal cells.</p><p><strong>Subjects: </strong>Biopsies from two healthy, reproductive-aged volunteers with regular menstrual cycles and no history of gynecological malignancies.</p><p><strong>Exposure: </strong>The ESR1-activated and control endometrial stromal cells were treated with estradiol (E2) or vehicle. Primary endometrial stromal cells were treated with vehicle or a decidualization cocktail.</p><p><strong>Main outcome measures: </strong>Differential gene expression analysis (RNA-seq) identified ligand-independent and -dependent ESR1 activity. Cut&Run profiled ESR1 genomic binding in ESR1-activated cells. H3K27ac HiChIP mapped hormone-induced changes in chromatin looping in primary cells.</p><p><strong>Results: </strong>Among seven tested guide RNAs (gRNA), the ESR1-3 gRNA induced robust ESR1 activation and restored E2 responsiveness. Bulk RNA-seq revealed both ligand-dependent and -independent ESR1 transcriptional programs regulating inflammation, proliferation, and cancer-related pathways. Notably, 72% of differentially expressed genes overlapped with genes active in human endometrial tissue during the proliferative estrogen-dominant phase, supporting their physiological relevance. The Cut&Run-seq identified genome-wide ESR1 binding sites, with most binding sites located at distal regulatory elements. Integration of Cut&Run data with H3K27ac HiChIP chromatin loops linked distal ESR1 binding sites to gene promoters, including genes involved in decidualization (e.g., FOXO1) and endometrial cancer (e.g., ERRFI1, NRIP1, and EPAS1). Functional assays showed that ESR1 promotes cell viability and, in the presence of E2, enhances migration.</p><p><strong>Conclusion: </strong>The CRISPR-mediated ESR1 activation restores estrogen responsiveness in endometrial stromal cells. Combined transcriptomic, cistromic, and chromatin architecture analyses reveal ESR1's role in regulating decidualization and inflammation-related gene networks, with relevance to endometrial pathologies including endometrial cancer. This model serves as a powerful tool to study estrogen signaling in endometrial stromal cell biology and related pathologies.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849965","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":"Fertilin peptide decreases embryo resorption and improves live birth rate in mouse.","authors":"Sophie Favier, Audrey L'Hostis, Rémi Pierre, Isabelle Lagoutte, Eric Vicaut, Daniel Vaiman, Jean Philippe Wolf","doi":"10.1016/j.xfss.2025.08.001","DOIUrl":"10.1016/j.xfss.2025.08.001","url":null,"abstract":"<p><strong>Objective: </strong>To study the effect of the mouse Fertilin peptide, on mouse in vitro and in utero embryo development.</p><p><strong>Design: </strong>The Fertilin peptide, a cyclic tripeptide derived from a loop of the ADAM2 protein, is already known to provide healthy pups over three generations of mice. The present prospective randomized study analyzes the in vitro and in vivo mouse embryo development using ultrasound examination, and birth rates, considering embryo resorption in mice as the equivalent of miscarriage in humans.</p><p><strong>Subjects: </strong>B6CBA F1 female mice were crossed with C57BL6/J male mice. A total of 458 day 2 embryos were retrieved and involved in the study: 150 for in vitro study, 66 for immunofluorescence, and 242 were transferred in vivo. INTERVENTION (FOR RESEARCH CLINICAL TRIAL) OR EXPOSURE (FOR OBSERVATIONAL STUDIES): Two-cell embryos were incubated in an embryoscope without or with the Fertilin peptide at 100 μM. The embryos were then either followed up in vitro until blastocyst formation, or were transferred in utero on day 3. Their development was analyzed using ultrasound examination. Birth rates were registered.</p><p><strong>Main outcome measures: </strong>The main outcomes are: (1) in vitro kinetics of embryo development in the control and Fertilin group, (2) in vivo development of embryos analyzed by ultrasound analysis. The pregnant female mice were kept separately so that newborns could be counted after they gave birth (3).</p><p><strong>Results: </strong>In mice, Fertilin 100 μM accelerated blastocyst formation in vitro, and reduced embryo resorption in vivo from 48.6% to 33.0%. Consistently, the live birth rate was increased from 42% to 63%.</p><p><strong>Conclusion: </strong>This study demonstrates that Fertilin peptide accelerates embryo development in vitro, reduces the resorption rate in utero, and increases the live birth rate in mice.</p><p><strong>Interpretation: </strong>In the mouse model, Fertilin appears to be the first molecule able to significantly reduce miscarriage in vivo and improve live birth rate. The human molecule is currently being evaluated in an ongoing prospective, randomized, multicenter clinical trial (NCT:04954274).</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818393","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":"Laparoscopic ovarian drilling vs. step-up gonadotropin therapy in infertile anovulatory polycystic ovary syndrome women resistant to sequential letrozole and gonadotropin-based ovulation induction cycles: a randomized controlled trial.","authors":"H V Bhavana, Reeta Mahey, Aarthi K Jayraj, Ashish Datt Upadhyay, Archana Kumari, Garima Kachhawa, Ayushi Negi, Khushbu Bashir, Srikar Yedlapalli","doi":"10.1016/j.xfss.2025.07.006","DOIUrl":"10.1016/j.xfss.2025.07.006","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To study the effect of laparoscopic ovarian drilling (LOD) vs. step-up gonadotropin therapy on follicular response in infertile anovulatory polycystic ovary syndrome (PCOS) women resistant to sequential letrozole + human menopausal gonadotropin (HMG)-based ovulation induction (OVI) cycles DESIGN: Open-labeled, pilot, randomized controlled trial SUBJECTS: Infertile anovulatory PCOS women (diagnosed according to modified Rotterdam criteria), resistant to sequential letrozole 5 mg + HMG-based OVI cycle (no dominant follicle &gt;10 mm after 14 days of stimulation). Other inclusion criteria were: age 19-38 years; body mass index ≤35 kg/m&lt;sup&gt;2&lt;/sup&gt;; patent fallopian tubes documented on either hysterosalpingography/saline infusion sonography or laparoscopy; antimüllerian hormone (AMH) levels &gt;6 ng/mL. Exclusion criteria were AMH ≤6 ng/mL; moderate to severe male factor infertility and endometriosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Intervention: &lt;/strong&gt;Participants in group 1 (N = 35) underwent LOD, after which OVI cycles were started with letrozole 5 mg from the following menses. Gonadotropin were added in a sequential manner if required as per the follicular response. Women in group 2 (N = 35) were administered injection of HMG (75 IU) from day 2 of menses and dose increments were done from day 9 onward as per response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;Primary outcome was follicular response (dominant follicle &gt;16 mm). Secondary objectives were gonadotropin requirement per cycle, duration of stimulation, time to conception (months), clinical pregnancy rate and ongoing pregnancy rate (&gt;12 weeks). The study also compared the effect of LOD on hormonal parameters (AMH, serum testosterone) and metabolic parameters (fasting insulin, fasting blood glucose, lipid profile, homeostasis model assessment of insulin resistance) after 1-2 months of procedure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Majority of the study participants (82.85%) belonged to PCOS phenotype A. The baseline clinical, hormonal, and metabolic characteristics and phenotype distribution were comparable in both groups. The follicular response was significantly higher in the LOD group (93.25%; 83/89) compared with step-up gonadotropin group (28.20%; 11/39). With four spontaneous conceptions, the median time to conception in LOD group was 3.9 (0-8.4) months. The clinical pregnancy rate per patient was significantly higher in LOD group [54.28% (19/35)] as compared with step-up gonadotropin group [8.57% (3/35)]. The ongoing pregnancy rate in the LOD group was 45.71% (16/35) vs. 0% (0/35) in the gonadotropin group. There was a significant fall in the AMH levels from 15.2 ± 2.7 ng/mL to 10.2 ± 4.4 ng/mL after LOD. Although statistically insignificant, the levels of luteinizing hormone/follicle-stimulating hormone ratio, testosterone, fasting insulin, fasting glucose and homeostasis model assessment of insulin resistance levels were also lowered.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;L","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786088","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 CYP19A1 genetic variations on polycystic ovary syndrome: findings from a case-control study","authors":"Hiral Chaudhary Ph.D. ,&nbsp;Jalpa Patel Ph.D. ,&nbsp;Nayan K. Jain Ph.D. ,&nbsp;Sonal Panchal M.D. ,&nbsp;Purvi Nanavati M.D. ,&nbsp;Mala Singh Ph.D. ,&nbsp;Naresh Laddha Ph.D. ,&nbsp;Rushikesh Joshi Ph.D.","doi":"10.1016/j.xfss.2025.03.005","DOIUrl":"10.1016/j.xfss.2025.03.005","url":null,"abstract":"<div><h3>Objective</h3><div>To study the association between <span><span>CYP19A1</span></span><span> genetic<span> variants and the risk of developing polycystic ovary syndrome (PCOS). The study explored the relationship between the candidate gene </span></span><em>CYP19A1</em><span> and hyperandrogenism, as well as its interplay with obesity, in PCOS patients compared with healthy controls.</span></div></div><div><h3>Design</h3><div><span><span>A case-control study with genetic association analysis by tetra-primer amplification refractory mutation system </span>polymerase chain reaction and </span>biochemical analysis.</div></div><div><h3>Subjects</h3><div>204 women (113 PCOS patients and 91 healthy controls) were included in the present study.</div></div><div><h3>Exposure</h3><div><em>CYP19A1</em> variants (rs700519 and rs2236722) in PCOS women.</div></div><div><h3>Main Outcome Measures</h3><div>Genotypic and allelic frequencies of <em>CYP19A1</em><span> variants (rs2236722 and rs700519) and their impact on androgen metabolism and obesity markers.</span></div></div><div><h3>Results</h3><div><span>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, </span>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.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the <em>CYP19A1</em> 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.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 364-373"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","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}

{"title":"Utilization of a three-dimensional in vitro co-culture system to characterize embryonic mechanisms associated with implantation","authors":"Keelee J. McCarty Ph.D.,&nbsp;Blair McCallie Ph.D.,&nbsp;William B. Schoolcraft M.D.,&nbsp;Mandy Katz-Jaffe Ph.D.","doi":"10.1016/j.xfss.2025.03.001","DOIUrl":"10.1016/j.xfss.2025.03.001","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Endometrial biopsies&lt;span&gt; were collected from fertile oocyte&lt;span&gt; donors to generate individual 3D wells of separated monolayers of luminal endometrial epithelial and stromal cells&lt;span&gt;&lt;span&gt; for co-culture with an individual blastocyst (n = 72; &lt;/span&gt;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).&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;N/A.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;N/A.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Immunohistochemistry&lt;span&gt; and targeted quantitative real-time polymerase chain reaction gene expression were performed on individual blastocysts and on exosome-purified small RNAs derived from supernatant.&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;span&gt;&lt;span&gt;After successful implantation into the endometrial epithelium&lt;span&gt;&lt;span&gt;, 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 &lt;/span&gt;gene expression analysis revealed an upward trend of implantation-promoting genes GATA &lt;/span&gt;&lt;/span&gt;binding protein 3, &lt;/span&gt;octamer binding transcription factor 4&lt;span&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;, and cell death regulatory gene&lt;span&gt; caspase &lt;/span&gt;&lt;/span&gt;protein 3 in correctly timed blastocysts compared with slower developing blastocysts. Interestingly, as blastocysts became more attached to the epithelium, a downward trend of &lt;/span&gt;developmental genes&lt;span&gt;&lt;span&gt; caudal-related homeobox 2 and &lt;/span&gt;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 &lt;/span&gt;&lt;/span&gt;microRNAs&lt;span&gt;&lt;span&gt; were axon guidance, ubiquitin-mediated &lt;/span&gt;proteolysis&lt;span&gt;&lt;span&gt;, and neurotrophin &lt;/span&gt;signaling pathway.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;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","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 312-320"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","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}

{"title":"Relationship between early and mid-lateal phase progesterone levels and the DNA methylation of WOI-related genes in cervical secretions in fresh and frozen IVF cycles","authors":"Cemil Kaya M.D. ,&nbsp;Kübra Nur Kaplan İlhan M.Sc. ,&nbsp;Bala Gur Dedeoglu Ph.D. ,&nbsp;Mehmet Erdem M.D. ,&nbsp;Ahmet Erdem M.D.","doi":"10.1016/j.xfss.2025.06.001","DOIUrl":"10.1016/j.xfss.2025.06.001","url":null,"abstract":"<div><h3>Objective</h3><div>To study the association between serum progesterone (P4) levels on the day of embryo transfer (ET) and the deoxyribonucleic acid methylation of window of implantation-related genes in cervical secretions, in both fresh and frozen ET cycles among women undergoing in vitro fertilization (IVF) treatment.</div></div><div><h3>Design</h3><div>Single-center retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Women undergoing ET cycles.</div></div><div><h3>Exposure</h3><div>Cervicovaginal materials have been used as a noninvasive surrogate in investigations of endometrial conditions and progesterone levels on the day of ET.</div></div><div><h3>Main Outcome Measures</h3><div>Progesterone levels and methylation changes.</div></div><div><h3>Results</h3><div>A total of 40 eligible women undergoing IVF-ET cycles were evaluated. On the basis of methylation analyses of <em>CXCL14</em>, <em>EMCN</em>, <em>RARRES1</em>, <em>PAEP</em>, <em>THBS2</em>, and <em>GPX3</em>, no statistically significant correlation was found with the median serum P4 levels on the day of ET. When participants were grouped into quartiles on the basis of P4 levels on the day of ET, no statistically significant differences were observed in the methylation levels of <em>CXCL14</em>, <em>SERPING1</em>, <em>EMCN</em>, <em>RARRES1</em>, <em>PAEP</em>, <em>THBS2</em>, and <em>GPX3</em>. The median P4 levels were significantly lower in the thawed ET group (median, 21.4 ng/mL; interquartile range, 13.3–24.0) than in the fresh transfer group (median, 24.0 ng/mL; interquartile range, 18.0–45.0). No significant differences in gene methylation levels were observed between fresh and thawed transfer types, except for <em>THBS2</em>, which showed significantly lower methylation levels in the thawed group than in the fresh group. Although the median P4 levels were lower on day 3 transfers (16.6 ng/mL) than on day 5 transfers (22.4 ng/mL), the difference was not statistically significant. Similarly, no significant differences in methylation levels were detected when comparing day 3 vs. day 5 ET groups.</div></div><div><h3>Conclusion</h3><div>No association was found between early and mid-luteal phase P4 levels and methylation changes of implantation-related genes in cervical secretions during both fresh and frozen IVF cycles.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 340-352"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512882","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}