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Reviewer of the Year. F&S Science celebrates excellence in our world class reviewers 2023 年度审稿人。F&S Science 为世界级审稿人的卓越表现喝彩。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.002
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引用次数: 0
Progesterone receptor status predicts aggressiveness of human endometriotic lesions in murine avatars 孕酮受体状态可预测小鼠子宫内膜异位症病变的侵袭性
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.004
Valerie A. Flores M.D., Cagdas Sahin M.D., Hugh S. Taylor M.D.

Objective

To use murine avatars for studying human endometriotic lesion response to 2 different hormonal regimens to determine whether progesterone receptor (PR) can prospectively predict response to progestin-based therapy. Endometriosis is a chronic gynecologic disease afflicting 1-in-10 reproductive-age women; however response to medical therapy is highly variable because endometriotic lesions do not consistently respond to first-line progestin-based therapy. We have previously demonstrated in a retrospective study that PR status in lesions is correlated with response to progestins. Here, we hypothesize that a prospective approach using PR status to predict response to medical will allow clinicians to individualize effective, timely treatment for this debilitating disease.

Design

Patient-derived xenograft murine model.

Subjects

Eight-week old NOD/SCID mice undergoing transplantation of endometrioma lesions collected from women undergoing surgery for endometriosis.

Exposure

Daily subcutaneous injections with vehicle (dimethyl sulfoxide), medroxyprogesterone acetate (MPA), or gonadotropin-releasing hormone (GnRH) antagonist, cetrorelix, for 1 month.

Main Outcome Measures

Lesion size 1 month after treatment.

Results

Lesions with high PR demonstrated a robust response to MPA compared with lesions with low PR. The mean post-MPA treatment size in high-PR lesions was sixfold smaller than that in low-PR lesions. Low-PR lesions respond far more completely to GnRH antagonist than to MPA. Surprisingly, there were differences in response to GnRH antagonist between low- and high-PR lesions. High-PR lesions responded almost completely to GnRH antagonist with a 21-fold smaller posttreatment size on average than low-PR lesions.

Conclusions

The use of murine avatars to test clinical response is a novel approach in endometriosis. Hormonal suppression of disease is a cornerstone of therapy; however, response is not fully predictable. We have previously shown that women with low-PR lesions respond poorly to progestin-based therapy. Here, we prospectively validate our previous work using a mouse xenograft model, demonstrating that lesions with low-PR expression do not respond to progestin-based therapy; PR status predicted response to progestin-based therapy. Moreover, PR status identifies a more aggressive form of endometriosis that is not only progesterone resistant but is also less dependent on estradiol for growth. Our findings highlight the need to develop novel nonhormonal therapies aimed at targeting the more aggressive forms of endometriosis that do not rely on the usual hormonal signals.
目的:利用小鼠化身研究人类子宫内膜异位症病变对两种不同激素疗法的反应:利用小鼠化身研究人类子宫内膜异位症病变对两种不同激素方案的反应,以确定PR能否前瞻性地预测对孕激素疗法的反应。子宫内膜异位症是一种慢性妇科疾病,每 10 名育龄妇女中就有 1 人患病;然而,由于子宫内膜异位症病变对基于孕激素的一线疗法的反应并不一致,因此对药物疗法的反应非常不稳定。我们曾在一项回顾性研究中证实,病变部位的孕酮受体(PR)状态与对孕激素的反应相关。在此,我们假设,利用 PR 状态来预测对药物的反应的前瞻性方法将使临床医生能够对这种使人衰弱的疾病进行有效、及时的个体化治疗:设计:患者衍生异种移植小鼠模型 对象:八周大的 NOD/SCID 小鼠八周大的 NOD/SCID 小鼠,接受从接受子宫内膜异位症手术的妇女身上收集的子宫内膜瘤病灶移植:每天皮下注射载体(DMSO)、醋酸甲羟孕酮(MPA)或GnRH拮抗剂西曲瑞克,为期1个月:结果:与 PR 值低的病变相比,PR 值高的病变对 MPA 的反应强烈。高 PR 病变在 MPA 治疗后的平均大小是低 PR 病变的 6 倍。低 PR 病变对 GnRH 拮抗剂的反应远比对 MPA 的反应完全。令人惊讶的是,低 PR 病变和高 PR 病变对 GnRH 拮抗剂的反应存在差异。与低 PR 病变相比,高 PR 病变对 GnRH 拮抗剂的反应几乎是完全的,治疗后的平均大小缩小了 21 倍:结论:使用小鼠化身测试临床反应是子宫内膜异位症的一种新方法。激素抑制疾病是治疗的基石,但反应并不能完全预测。我们以前的研究表明,低 PR 病变的妇女对孕激素治疗的反应很差。在这里,我们利用小鼠异种移植模型对之前的工作进行了前瞻性验证,证明低 PR 表达的病变对孕激素治疗没有反应;PR 状态可预测对孕激素治疗的反应。此外,PR 状态还能确定一种更具侵袭性的子宫内膜异位症,这种子宫内膜异位症不仅对孕激素有抵抗力,而且其生长对雌二醇的依赖性也较低。我们的研究结果凸显了开发新型非激素疗法的必要性,这些疗法旨在针对不依赖于常规激素信号的更具侵袭性的子宫内膜异位症。
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引用次数: 0
P2X4 receptor mediates macrophage infiltration leading to endometriotic cyst epithelium proliferation and hyperalgesia in mouse model P2X4 受体在小鼠模型中介导巨噬细胞浸润,导致子宫内膜异位囊肿上皮细胞增殖和痛觉减退。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.007
Hiroki Nagata M.D. , Takeshi Y. Hiyama Ph.D. , Misaki Inoue B.Sc. , Shanshan Xu M.Sc. , Ikumi Wada M.D. , Yuki Yoshimura Ph.D. , Kazuomi Nakamura Ph.D. , Yukihiro Azuma M.D. Ph.D. , Tasuku Harada M.D., Ph.D. , Fuminori Taniguchi M.D., Ph.D.

Objective

To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.

Design

Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.

Results

NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.

Conclusion

These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.
目的评估 P2X4 受体(P2X4R)特异性拮抗剂对小鼠子宫内膜异位症样病变和人类子宫内膜异位症基质细胞的影响:设计:使用体内小鼠子宫内膜异位症模型和体外原代培养的人类子宫内膜异位基质细胞进行实验研究。给小鼠和细胞口服 P2X4 离子型 ATP 受体(P2X4R)拮抗剂 NC-2600。对小鼠的子宫内膜异位症样囊肿和阴道部分进行了细胞因子基因表达分析,并进行了免疫组化,以评估巨噬细胞的增殖活性和定位情况以及细胞因子的表达情况。小鼠阴道疼痛的感觉是通过视觉运动反应来评估的:研究在学术和医院研究实验室进行:结果:NC-2600能减少囊肿上皮细胞的增殖和阴道疼痛感。在子宫内膜异位症动物的囊肿和阴道中,P2X4R主要在巨噬细胞中表达,NC-2600能减少组织巨噬细胞的数量,并逆转白细胞介素L-33和环氧化酶-2的升高表达:这些结果表明,在子宫内膜异位症损伤部位和阴道的局部巨噬细胞中表达的 P2X4R 具有未知的病理生理作用,这表明口服 P2X4R 抑制剂对缓解子宫内膜异位症症状具有潜在的治疗作用。
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引用次数: 0
Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome 在青少年和卵母细胞捐献者的卵泡液中检测到邻苯二甲酸盐,并伴随着积液细胞转录组的变化。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.009
Dilan Gokyer M.D. , Mary J. Laws Ph.D. , Anna Kleinhans B.S. , Joan K. Riley Ph.D., H.C.L.D. , Jodi A. Flaws Ph.D. , Elnur Babayev M.D., M.Sc.

Objective

To investigate the follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared with oocyte donors and explore its association with ovarian reserve and cumulus cell (CC) gene expression.

Design

Retrospective study and molecular analysis of CCs and FF.

Subjects

Adolescents (n = 20, 16.7 ± 0.6 years) undergoing fertility preservation and oocyte donors (n = 24, 26.2 ± 0.4 years).

Exposure

Not applicable.

Main Outcome Measures

Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were analyzed for each group. The FF levels of 9 phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates, ƩPhthalates; di(2-ethylhexyl) phthalate (DEHP)–associated phthalate metabolites, ƩDEHP), exposure sources (plastics, ƩPlastic; personal care products, ƩPCP), and modes of action (antiandrogenic, ƩAA) and compared between the 2 groups. The transcriptome of CC associated with mature oocytes was compared between adolescents and oocyte donors using bulk ribonucleic acid sequencing.

Results

The FF ƩPlastic and ƩPCP levels were significantly higher in adolescents than in oocyte donors. The FF ƩDEHP, ƩPlastic, ƩPCP, ƩAA, and ƩPhthalates levels were positively associated with antral follicle count in oocyte donors when adjusted for age, body mass index, and race/ethnicity. Ribonucleic acid sequencing analysis revealed 248 differentially expressed genes in CCs of adolescents within the top quartile (n = 4) of the FF ƩPhthalates levels compared with those of the adolescents within the bottom half (n = 9). Genes enriched in pathways involved in cell motility and development were significantly down-regulated.

Conclusions

Adolescents undergoing fertility preservation cycles demonstrate higher levels of phthalate metabolites in their FF than oocyte donors. Higher phthalate levels are associated with alterations in cumulus cells transcriptome in adolescents. The phthalate metabolite levels in FF are associated with higher antral follicle count levels in oocyte donors.
目的调查与卵母细胞捐献者相比,接受生育力保存的青少年卵泡液(FF)中的邻苯二甲酸酯水平,并探讨其与卵巢储备和积液细胞基因表达的关系:设计:回顾性研究,对积液细胞(CCs)和FF进行分子分析:接受生育力保存的青少年(20 人,16.7 ± 0.6 岁)和卵母细胞捐献者(24 人,26.2 ± 0.4 岁):对每组患者的人口统计学、卵巢刺激和卵母细胞获取结果进行分析。对9种邻苯二甲酸酯代谢物的FF水平进行了单独评估,并将其作为代表常见化合物的摩尔总和进行评估(所有邻苯二甲酸酯代谢物的FF水平均为±0.4%):Ʃ邻苯二甲酸盐;邻苯二甲酸二(2-乙基己基)酯(DEHP)相关邻苯二甲酸盐代谢物:ƩDEHP)、暴露源(塑料:ƩPlastic;个人护理产品:ƩPCP)和作用模式(抗雄激素:ƩAA),并在两组之间进行比较。使用大容量RNA测序技术比较了青少年与卵母细胞捐献者之间与成熟卵母细胞相关的CC转录组:结果:与卵母细胞捐献者相比,青少年卵泡液中的ƩPlastic和ƩPCP水平明显更高(pConclusion):与卵细胞捐献者相比,接受生育力保存周期的青少年卵泡液中邻苯二甲酸酯代谢物的水平更高。卵泡液中的邻苯二甲酸酯代谢物水平与卵母细胞捐献者较高的 AFC 水平有关。
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引用次数: 0
Unraveling the genetic basis of azoospermia: transcriptome profiling analyses in a Greek population 揭示无精子症的遗传基础:希腊人群的 RNA 序列和转录组特征分析。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.008
Alexandra Chatziparasidou M.Sc. , Theologia Sarafidou Ph.D. , Maria-Anna Kyrgiafini Ph.D. , Katerina Moutou Ph.D. , Maria Markantoni Ph.D. , Themistoklis Giannoulis Ph.D. , Achilleas Papatheodorou Ph.D. , Chara Oraiopoulou M.Sc. , Glykeria Samolada M.Sc. , Nikos Christoforidis M.D. , Zissis Mamuris Ph.D.

Objective

To investigate whether idiopathic nonobstructive azoospermia (iNOA) has its own transcriptomic signature.

Design

Testicular tissue biopsies were retrieved, processed, and prepared for ribonucleic acid (RNA) extraction from 26 consented patients diagnosed with iNOA. Samples were grouped into four pools based on the presence of testicular spermatozoa: two replicate pools for “No presence” (Null-spz-1 and Null-spz-2 pools), one for “High presence” (High-spz pool), and one for “Rare presence” (Rare-spz pool). A second set of replicate pools (CF-1 and CF-2) were used from patients with obstructive azoospermia (OA) and served as controls. RNA sequencing (RNA-seq) and comparative transcriptomics analysis were performed, followed by differential gene expression analysis focused on protein-coding genes only. Differentially expressed genes (DEGs) exclusively upregulated or downregulated were further analyzed using the Gene Ontology (GO), STRING, and Kyoto Encyclopedia of Genes and Genome bioinformatic platforms.

Subjects

Males in whom iNOA was diagnosed.

Exposure

Testicular biopsies from men in whom iNOA was diagnosed.

Main Outcome Measures

Protein-coding DEGs.

Results

A significantly altered transcriptomic profile of protein-coding genes was identified in the testicular tissues from men with iNOA. A total of 3,858 genes exhibited dysregulated expression, with 1,994 genes being exclusively downregulated and 1,734 upregulated. Biological processes such as male gamete generation (GO:0048232) and meiotic cycle (GO:0051321) were significantly enriched by the downregulated DEGs whereas the upregulated DEGs enriched BPs such as regulation of cell death (GO:0010941), regulation of cell adhesion (GO:0030155), and defense response (GO:0006952). Interactome analysis identified hub genes among the downregulated DEGs, including PCNA, PLK1, MCM4, CDK1, CCNB1, AURKA, CCNA2, and CDC6, and among the upregulated DEGs, including EGFR, RELA, CTNNB1, MYC, JUN, SMAD3, STAT3 NFKB1, TGFB1, and ACTB. In addition, Kyoto Encyclopedia of Genes and Genome analysis demonstrated that pathways such as cell cycle (hsa04110) and oocyte meiosis (hsa04114) are primarily affected by the downregulated genes, whereas the upregulated genes mainly affected pathways such as the focal adhesion (hsa04510) and the PI3-Akt signaling pathway (hsa04151).

Conclusion

A distinct messenger RNA expression profile and altered transcriptomic activity were identified in the testicular tissues of men with iNOA.

Clinical Trial Registration Number

University of Thessaly 1, 15.04.2016 and the Greek National Authority 701/15.9.2017.
目的研究特发性非梗阻性无精子症(iNOA)是否有自己的转录组特征:设计:对 26 名经同意诊断为特发性非梗阻性无精子症(iNOA)的患者的睾丸组织活检样本进行检索、处理并准备提取 RNA。根据睾丸精子的存在情况将样本分为四个池:两个 "无精子存在 "池(Null-spz-1 和 Null-spz-2 池)、一个 "高精子存在 "池(High-spz 池)和一个 "罕见精子存在 "池(Rare-spz 池)。第二组复制池(CF-1 和 CF-2)来自梗阻性无精子症(OA)患者,作为对照。进行了 RNA 测序(RNA-seq)和比较转录组学分析(CTA),然后只对蛋白编码基因进行了差异基因表达分析(DGE)。使用基因本体(GO)、STRING和京都基因组百科全书(KEGG)生物信息平台进一步分析了专门上调或下调的差异表达基因(DEGs):受试者:确诊为 iNOA 的男性。暴露:确诊为 iNOA 的男性的睾丸活检组织:主要结果指标:蛋白质编码差异表达基因(DEGs):结果:在患有 iNOA 的男性的睾丸组织中,蛋白质编码基因的转录组概况发生了明显改变。共有 3858 个基因表现出表达失调,其中 1994 个基因完全下调,1734 个基因上调。下调的 DEGs 显著富集了雄性配子生成(GO:0048232)和减数分裂周期(GO:0051321)等生物过程(BPs),而上调的 DEGs 则富集了细胞死亡调控(GO:0010941)、细胞粘附调控(GO:0030155)和防御反应(GO:0006952)等生物过程(BPs)。互作组分析确定了下调 DEGs 中的枢纽基因,包括 PCNA、PLK1、MCM4、CDK1、CCNB1、AURKA、CCNA2 和 CDC6,以及上调 DEGs 中的枢纽基因,包括表皮生长因子受体、RELA、CTNNB1、MYC、JUN、SMAD3、STAT3 NFKB1、TGFB1 和 ACTB。此外,KEGG分析表明,下调基因主要影响细胞周期(hsa04110)和卵母细胞减数分裂(hsa04114)等通路,而上调基因主要影响病灶粘附(hsa04510)和PI3-Akt信号通路(hsa04151)等通路:结论:在患有 iNOA 的男性睾丸组织中发现了独特的 mRNA 表达谱和转录组活性的改变。
{"title":"Unraveling the genetic basis of azoospermia: transcriptome profiling analyses in a Greek population","authors":"Alexandra Chatziparasidou M.Sc. ,&nbsp;Theologia Sarafidou Ph.D. ,&nbsp;Maria-Anna Kyrgiafini Ph.D. ,&nbsp;Katerina Moutou Ph.D. ,&nbsp;Maria Markantoni Ph.D. ,&nbsp;Themistoklis Giannoulis Ph.D. ,&nbsp;Achilleas Papatheodorou Ph.D. ,&nbsp;Chara Oraiopoulou M.Sc. ,&nbsp;Glykeria Samolada M.Sc. ,&nbsp;Nikos Christoforidis M.D. ,&nbsp;Zissis Mamuris Ph.D.","doi":"10.1016/j.xfss.2024.10.008","DOIUrl":"10.1016/j.xfss.2024.10.008","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether idiopathic nonobstructive azoospermia (iNOA) has its own transcriptomic signature.</div></div><div><h3>Design</h3><div>Testicular tissue biopsies were retrieved, processed, and prepared for ribonucleic acid (RNA) extraction from 26 consented patients diagnosed with iNOA. Samples were grouped into four pools based on the presence of testicular spermatozoa: two replicate pools for “No presence” (Null-spz-1 and Null-spz-2 pools), one for “High presence” (High-spz pool), and one for “Rare presence” (Rare-spz pool). A second set of replicate pools (CF-1 and CF-2) were used from patients with obstructive azoospermia (OA) and served as controls. RNA sequencing (RNA-seq) and comparative transcriptomics analysis were performed, followed by differential gene expression analysis focused on protein-coding genes only. Differentially expressed genes (DEGs) exclusively upregulated or downregulated were further analyzed using the Gene Ontology (GO), STRING, and Kyoto Encyclopedia of Genes and Genome bioinformatic platforms.</div></div><div><h3>Subjects</h3><div>Males in whom iNOA was diagnosed.</div></div><div><h3>Exposure</h3><div>Testicular biopsies from men in whom iNOA was diagnosed.</div></div><div><h3>Main Outcome Measures</h3><div>Protein-coding DEGs.</div></div><div><h3>Results</h3><div>A significantly altered transcriptomic profile of protein-coding genes was identified in the testicular tissues from men with iNOA. A total of 3,858 genes exhibited dysregulated expression, with 1,994 genes being exclusively downregulated and 1,734 upregulated. Biological processes such as male gamete generation (GO:0048232) and meiotic cycle (GO:0051321) were significantly enriched by the downregulated DEGs whereas the upregulated DEGs enriched BPs such as regulation of cell death (GO:0010941), regulation of cell adhesion (GO:0030155), and defense response (GO:0006952). Interactome analysis identified hub genes among the downregulated DEGs, including PCNA, PLK1, MCM4, CDK1, CCNB1, AURKA, CCNA2, and CDC6, and among the upregulated DEGs, including EGFR, RELA, CTNNB1, MYC, JUN, SMAD3, STAT3 NFKB1, TGFB1, and ACTB. In addition, Kyoto Encyclopedia of Genes and Genome analysis demonstrated that pathways such as cell cycle (hsa04110) and oocyte meiosis (hsa04114) are primarily affected by the downregulated genes, whereas the upregulated genes mainly affected pathways such as the focal adhesion (hsa04510) and the PI3-Akt signaling pathway (hsa04151).</div></div><div><h3>Conclusion</h3><div>A distinct messenger RNA expression profile and altered transcriptomic activity were identified in the testicular tissues of men with iNOA.</div></div><div><h3>Clinical Trial Registration Number</h3><div>University of Thessaly 1, 15.04.2016 and the Greek National Authority 701/15.9.2017.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 16-29"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sphingosine 1-phosphate acts as proliferative and fibrotic cue in leiomyoma cells 鞘氨醇1-磷酸在平滑肌瘤细胞中起增殖和纤维化作用。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.11.003
Margherita Rossi M.Sc. , Isabelle Seidita Ph.D. , Matteo Prisinzano M.Sc. , Maryam Raeispour M.Sc. , Lucia Romeo M.Sc. , Flavia Sorbi M.D. , Massimiliano Fambrini M.D. , Pasquapina Ciarmela Ph.D. , Felice Petraglia M.D. , Caterina Bernacchioni Ph.D. , Chiara Donati Ph.D.

Objective

To determine whether the bioactive sphingolipid sphingosine 1-phosphate (S1P) modulates cellular proliferation and synthesis of fibrotic proteins in leiomyoma differently than myometrial cells.

Design

A basic science study using human leiomyoma and myometrial cells.

Subjects

Not applicable. This is an in vitro study performed on cellular models.

Exposure

Leiomyoma and myometrial cells were treated with S1P, as well as with selective antagonists for S1P-specific G protein–coupled receptors and secondarily with inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and ezrin.

Main Outcome Measures

The main outcome measures included cellular proliferation and fibrogenesis. Bromodeoxyuridine Cell Proliferation Assay was employed to measure deoxyribonucleic acid synthesis and proliferation, whereas western blot analysis was used to assess the expression of the fibrotic markers N-cadherin, α-smooth muscle actin, transgelin, and collagen type I alpha 1.

Results

Sphingosine 1-phosphate stimulates cellular proliferation of leiomyoma but not myometrial cells. The mitogenic effect elicited by S1P relies on the engagement of its specific receptor S1P2 and is mediated by ERK1/2 and ezrin activation. Furthermore, S1P exerts a profibrotic effect in a S1P-specific G protein–coupled receptor–dependent manner in leiomyoma but not myometrial cells.

Conclusions

These results, besides extending the knowledge on the molecular mechanism underlying uterine leiomyoma development and fibrosis, demonstrate the pathogenetic role of S1P in leiomyoma and support the rationale for targeting S1P signaling pathway as innovative potential treatment.
目的:探讨生物活性鞘脂鞘苷1-磷酸(S1P)对平滑肌瘤细胞增殖和纤维化蛋白合成的调节作用是否与子宫肌瘤细胞不同。设计:一项使用人类平滑肌瘤和子宫肌瘤细胞的基础科学研究。设置:学术实验室。暴露:用S1P、S1P特异性g蛋白偶联受体(S1PR)的选择性拮抗剂和细胞外信号调节激酶1/2 (ERK1/2)和ezrin抑制剂治疗平滑肌瘤和子宫内膜细胞。主要观察指标:细胞增殖和纤维形成。采用溴脱氧尿苷(BrdU)细胞增殖法检测细胞DNA合成和增殖情况,Western Blot法检测纤维化标志物N-cadherin、α -平滑肌肌动蛋白(αSMA)、transgelin和I型胶原α 1的表达情况。结果:S1P刺激平滑肌瘤细胞增殖,但对子宫肌瘤细胞无刺激作用。S1P诱导的有丝分裂作用依赖于其特异性受体S1P2的特异性参与,并通过ERK1/2和ezrin激活介导。此外,S1P在平滑肌瘤中以s1pr依赖的方式发挥促纤维化作用,而不是子宫肌瘤细胞。结论:这些结果除了扩展了对子宫平滑肌瘤发展和纤维化的分子机制的认识外,还证明了S1P在平滑肌瘤中的病理作用,并支持了靶向S1P信号通路作为创新潜在治疗方法的理论基础。
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引用次数: 0
A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment BCL6的ReceptivaDx阳性结果与ERA结果异常或受孕率相关标记物表达减少无关:这是生育评估和治疗中子宫内膜受孕率问题的两个方面。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.005
David Huang M.D. , Emily Flynn Ph.D , Ana Almonte-Loya B.S. , Brittany Davidson B.S. , Meagan Chan D.N.P. , Amber Casillas B.S. , Juan C. Irwin M.D., Ph.D. , Gabriela K. Fragiadakis Ph.D. , Hakan Cakmak M.D. , Alexis J. Combes Ph.D. , Marcelle I. Cedars M.D. , Marina Sirota Ph.D. , Linda C. Giudice M.D., Ph.D.
<div><h3>Objective</h3><div>To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.</div></div><div><h3>Design</h3><div>Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.</div></div><div><h3>Subjects</h3><div>Patients with infertility who underwent endometrial biopsy for concurrent endometrial receptivity array analysis (ERA; Igenomix, Valencia, Spain) and BCL6 immunostaining (ReceptivaDx; Cicero Diagnostics, Inc., Huntington Beach, CA).</div></div><div><h3>Exposure</h3><div>Positive BCL6 result on ReceptivaDx (histologic score >1.4).</div></div><div><h3>Main Outcome Measures</h3><div>Prereceptive ERA result; relative expression levels of endometrial receptivity-associated epithelial genes by single-nucleus sequencing.</div></div><div><h3>Results</h3><div>One hundred and seventy-two patients with concurrent ERA and ReceptivaDx evaluation were included in the analysis: 40 were BCL6-positive and 132 were BCL6-negative. One patient (2.5%) in the BCL6-positive group had a prereceptive ERA result, compared with 29 patients (22.0%) in the BCL6-negative group (<em>P</em><.01). BCL6 positivity was associated with decreased odds of a prereceptive ERA result (odds ratio, 0.09; 95% confidence interval, 0.01–0.69; <em>P</em>=.02). Single-nucleus transcriptomic analysis of 5,718 epithelial cell nuclei from four individuals showed significant cell type-specific transcriptomic changes associated with a positive ReceptivaDx BCL6 result in both natural cycle (NC) and programmed cycle (PC) endometrium: there were 2,801 significantly differentially expressed genes comparing NC BCL6-positive with -negative, and 1,062 differentially expressed genes comparing PC BCL6-positive with -negative. Of the 34 receptivity-associated epithelial markers evaluated, 16 were significantly upregulated in NC BCL6-positive vs. -negative endometrium epithelial nuclei. In PC epithelial nuclei, 12 of the 34 receptivity-associated genes were significantly upregulated, whereas only one was significantly downregulated in BCL6-positive vs. -negative endometrium.</div></div><div><h3>Conclusions</h3><div>A positive ReceptivaDx BCL6 result does not correlate with a prereceptive ERA. Epithelial cells from BCL6-positive endometrium did not show significantly decreased expression in most of the receptivity markers evaluated. These findings demonstrate discordance between the interpretation of “endometrial receptivity” by ReceptivaDx and ERA, and highlight the need for further validation of endometrial evaluation methods in fertility treatment.</div></d
目的利用子宫内膜接受性阵列和单核转录组学分析,研究 ReceptivaDx 评估 B 细胞淋巴瘤 6 (BCL6)(一种与子宫接受性受损相关的孕酮抗性拟议标记物)的阳性结果是否与植入窗中接受性相关标记物的次优特征相关:回顾性临床队列研究;对接受ReceptivaDx BCL6评估的前瞻性收集的植入窗子宫内膜进行单核RNA测序的试点研究 设置: 学术中心对象: 接受ReceptivaDx BCL6评估的不孕症患者:接受子宫内膜活检,同时进行子宫内膜受体阵列分析(ERA®;Igenomix)和BCL6免疫染色(ReceptivaDx™;Cicero Diagnostics, Inc.)的不孕症患者:ReceptivaDx™的BCL6阳性结果(组织学评分'HSCORE'>1.4) 主要结局指标:接受前ERA结果;通过单核测序检测子宫内膜接受性相关上皮基因的相对表达水平 结果:172例同时接受ERA和ReceptivaDx评估的患者纳入分析:40例BCL6阳性,132例BCL6阴性。BCL6阳性组中有一名患者(2.5%)的ERA结果为阳性,而BCL6阴性组中有29名患者(22.0%)的ERA结果为阴性:ReceptivaDx BCL6阳性结果与接受前ERA结果无关。BCL6 阳性子宫内膜的上皮细胞在大多数受孕标记物的表达上都没有明显下降。这些发现表明 ReceptivaDx 和 ERA 对 "子宫内膜接受性 "的解释不一致,并强调了在生育治疗中进一步验证子宫内膜评估方法的必要性。
{"title":"A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment","authors":"David Huang M.D. ,&nbsp;Emily Flynn Ph.D ,&nbsp;Ana Almonte-Loya B.S. ,&nbsp;Brittany Davidson B.S. ,&nbsp;Meagan Chan D.N.P. ,&nbsp;Amber Casillas B.S. ,&nbsp;Juan C. Irwin M.D., Ph.D. ,&nbsp;Gabriela K. Fragiadakis Ph.D. ,&nbsp;Hakan Cakmak M.D. ,&nbsp;Alexis J. Combes Ph.D. ,&nbsp;Marcelle I. Cedars M.D. ,&nbsp;Marina Sirota Ph.D. ,&nbsp;Linda C. Giudice M.D., Ph.D.","doi":"10.1016/j.xfss.2024.10.005","DOIUrl":"10.1016/j.xfss.2024.10.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Patients with infertility who underwent endometrial biopsy for concurrent endometrial receptivity array analysis (ERA; Igenomix, Valencia, Spain) and BCL6 immunostaining (ReceptivaDx; Cicero Diagnostics, Inc., Huntington Beach, CA).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;Positive BCL6 result on ReceptivaDx (histologic score &gt;1.4).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Prereceptive ERA result; relative expression levels of endometrial receptivity-associated epithelial genes by single-nucleus sequencing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;One hundred and seventy-two patients with concurrent ERA and ReceptivaDx evaluation were included in the analysis: 40 were BCL6-positive and 132 were BCL6-negative. One patient (2.5%) in the BCL6-positive group had a prereceptive ERA result, compared with 29 patients (22.0%) in the BCL6-negative group (&lt;em&gt;P&lt;/em&gt;&lt;.01). BCL6 positivity was associated with decreased odds of a prereceptive ERA result (odds ratio, 0.09; 95% confidence interval, 0.01–0.69; &lt;em&gt;P&lt;/em&gt;=.02). Single-nucleus transcriptomic analysis of 5,718 epithelial cell nuclei from four individuals showed significant cell type-specific transcriptomic changes associated with a positive ReceptivaDx BCL6 result in both natural cycle (NC) and programmed cycle (PC) endometrium: there were 2,801 significantly differentially expressed genes comparing NC BCL6-positive with -negative, and 1,062 differentially expressed genes comparing PC BCL6-positive with -negative. Of the 34 receptivity-associated epithelial markers evaluated, 16 were significantly upregulated in NC BCL6-positive vs. -negative endometrium epithelial nuclei. In PC epithelial nuclei, 12 of the 34 receptivity-associated genes were significantly upregulated, whereas only one was significantly downregulated in BCL6-positive vs. -negative endometrium.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A positive ReceptivaDx BCL6 result does not correlate with a prereceptive ERA. Epithelial cells from BCL6-positive endometrium did not show significantly decreased expression in most of the receptivity markers evaluated. These findings demonstrate discordance between the interpretation of “endometrial receptivity” by ReceptivaDx and ERA, and highlight the need for further validation of endometrial evaluation methods in fertility treatment.&lt;/div&gt;&lt;/d","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 55-64"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bleomycin in vitro exposure decreases markers of human male gamete competence 博莱霉素体外暴露会降低人类男性配子能力的标志物。
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.10.003
Ana Lobo de Almeida M.Sc. , Ana Gonçalves M.Sc. , Alberto Barros M.D., Ph.D. , Mário Sousa M.D., Ph.D. , Rosália Sá M.D., Ph.D.

Objective

To investigate the in vitro impact of bleomycin on human sperm deoxyribonucleic acid (DNA) integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients’ reproductive function.

Design

Controlled laboratory-based in vitro investigation.

Subjects

Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters after clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both.

Exposure

After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium, and exposed to bleomycin (100 μg/mL) for 2 hours at 37 °C in a humidified incubator with 5% CO2.

Main Outcome Measures

In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with sperm preparation medium, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays.

Results

Exposure to bleomycin for 2 hours in vitro significantly decreased sperm vitality, motility, and chromatin condensation compared with raw and control sperm. It also significantly increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly retarded the acrosomal response compared with control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations.

Conclusions

Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that patients with cancer undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.
目的:研究博莱霉素对人类精子DNA完整性、功能和形态的体外影响:研究博莱霉素对人类精子DNA完整性、功能和形态的体外影响,旨在阐明其潜在机制并预测对患者生殖功能的潜在影响:设计:实验室体外对照研究:45名育龄参与者捐献的多余人类射精用于研究,这些参与者在临床精液分析后显示出正常无精症精子参数。所有参与者均未接受过癌症诊断,也未接受过放疗、化疗或同时接受这两种治疗:临床精液分析后,对精子样本进行离心,在精子制备培养基(SPM)中稀释,并在37ºC、5% CO2的加湿培养箱中接触博莱霉素(100 μg/mL)两小时:主要结果指标:通过比较原始精子、经 SPM 培养的精子和暴露于博莱霉素的精子,对体外人类精子能力进行评估。能力指标包括精子运动能力、活力、DNA和顶体完整性以及线粒体膜电位。透射电子显微镜将超微结构形态学结果与功能测定结果联系起来:结果:与未处理精子和对照精子相比,体外暴露于博莱霉素两小时会显著降低精子活力、运动能力和染色质凝集(P < 0.001)。博莱霉素还能明显(P < 0.001)增加精子的DNA碎片和线粒体膜电位低的精子比例。此外,与对照组相比,博莱霉素明显(P < 0.05)延缓了顶体反应,但不影响细胞内和细胞外活性氧的形成。博莱霉素诱导的超微结构形态学变化支持了检测到的功能性改变:博莱霉素对人类男性配子能力有负面影响。结论:博莱霉素对人类男性配子能力有负面影响,医护人员应警惕并进一步研究博莱霉素的性腺毒性影响。同时,建议接受博莱霉素化疗方案的癌症患者接受生育力保护策略指导。
{"title":"Bleomycin in vitro exposure decreases markers of human male gamete competence","authors":"Ana Lobo de Almeida M.Sc. ,&nbsp;Ana Gonçalves M.Sc. ,&nbsp;Alberto Barros M.D., Ph.D. ,&nbsp;Mário Sousa M.D., Ph.D. ,&nbsp;Rosália Sá M.D., Ph.D.","doi":"10.1016/j.xfss.2024.10.003","DOIUrl":"10.1016/j.xfss.2024.10.003","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the in vitro impact of bleomycin on human sperm deoxyribonucleic acid (DNA) integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients’ reproductive function.</div></div><div><h3>Design</h3><div>Controlled laboratory-based in vitro investigation.</div></div><div><h3>Subjects</h3><div>Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters after clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both.</div></div><div><h3>Exposure</h3><div>After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium, and exposed to bleomycin (100 μg/mL) for 2 hours at 37 °C in a humidified incubator with 5% CO<sub>2</sub>.</div></div><div><h3>Main Outcome Measures</h3><div>In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with sperm preparation medium, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays.</div></div><div><h3>Results</h3><div>Exposure to bleomycin for 2 hours in vitro significantly decreased sperm vitality, motility, and chromatin condensation compared with raw and control sperm. It also significantly increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly retarded the acrosomal response compared with control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations.</div></div><div><h3>Conclusions</h3><div>Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that patients with cancer undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 5-15"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis 女性不孕症中的血源性炎症标志物:孟德尔随机分析的证据
Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.11.001
Simon Alesi B.Med.Sc. (Hons) , Helena Teede Ph.D. , Joanne Enticott Ph.D. , Kushan De Silva Ph.D. , Aya Mousa Ph.D.

Objective

To investigate causal associations between blood-based inflammatory markers and female infertility using Mendelian randomization (MR).

Design

Mendelian randomization using genome-wide association study data.

Subjects

Large female-only cohorts of European ancestry.

Exposure

Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ).

Main Outcome Measures

Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments.

Results

Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04–2.21) and weighted median (1.64, 1.05–2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13–3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59–0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83–0.97).

Conclusions

This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.
目的利用孟德尔随机化(Mendelian Randomisation,MR)方法调查血液中炎症标记物与女性不孕症之间的因果关系:设计:利用全基因组关联研究数据进行MR研究:暴露:主要结果测量:无排卵性不孕症(1054例,对照组117098例);其他/不明原因的女性不孕症(5667例,对照组117098例);女性不孕症的医学治疗(2706例,对照组120873例)。采用单变量双样本方法评估了总的因果效应,包括作为主要分析的逆方差加权(IVW),以及其他辅助分析(孟德尔随机化-艾格(MRE)、加权中位数(WMe)等),并进行了相关的质量评估:通过 IVW(几率比,95% 置信区间:1.51 [1.04, 2.21],P=0.032)和 WMe(1.64 [1.05, 2.57],P=0.028)方法,白细胞介素-8 与无排卵性不孕呈正相关。通过 MRE,单核细胞趋化蛋白-1 与无排卵性不孕相关(2.06 [1.13, 3.77],P=0.038)。通过 IVW 发现白细胞介素-12 和白细胞介素-18 呈反向关系,白细胞介素-12 较高与较低的女性不孕症医疗相关(0.75 [0.59, 0.94],p=0.013),而白细胞介素-18 较高与较低的其他/不明原因女性不孕症相关(0.90 [0.83, 0.97],p=0.008):这是首次使用磁共振成像技术研究炎症与女性不孕之间的因果关系。单核细胞趋化蛋白-1和白细胞介素-8与无排卵性不孕有关;但在主要分析中,只有白细胞介素-8与无排卵性不孕有明显关系。白细胞介素-12 和白细胞介素-18 与不孕症结果呈反向关系。需要进一步研究这些标志物的机理功能,以确认因果关系并研究它们对女性不孕症的治疗潜力。
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引用次数: 0
Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos. 多囊卵巢综合征与形态动力学胚胎发育:791个胚胎的病例对照研究。
Pub Date : 2025-01-19 DOI: 10.1016/j.xfss.2025.01.003
Gilad Karavani, Shira Shapira-Nass, Natali Schachter-Safrai, Tal Imbar, Assaf Ben-Meir

Objective: 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.

Design: A retrospective case-control study conducted in a university-affiliated in vitro fertilization (IVF) unit.

Patients: 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.

Exposure: Not applicable.

Main outcome measures: Embryo development morphokinetic parameters in women with and without PCOS undergoing IVF treatments.

Results: 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 >75th percentile.

Conclusion: 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.

目的:应用延时监测系统(TLM)探讨多囊卵巢综合征(PCOS)与机械性(输卵管)因素不孕妇女胚胎发育速率的关系。设计:在一所大学附属试管婴儿单位进行的回顾性病例对照研究。患者:接受体外受精(IVF)治疗的多囊卵巢综合征(PCOS)妇女和仅伴有输卵管因素不孕的非PCOS对照者。对发育形态动力学里程碑进行了比较,并对不同细胞数量的时间协方差进行了分析,并对逻辑混合模型进行了分析,以确定超过75百分位的胚胎预测因子。暴露:不适用。主要观察指标:接受体外受精治疗的多囊卵巢综合征和非多囊卵巢综合征妇女的胚胎发育形态动力学参数。结果:该研究包括115名妇女的791个胚胎,52名多囊卵巢综合征妇女的364个胚胎和63名非多囊卵巢综合征妇女输卵管性不孕的427个胚胎。PCOS组比PCOS组年轻4岁(30.07±6.03岁比34.08±4.84岁,p=0.002),取卵数较高(16.00比11.00,p= 75百分位)。结论:本研究证明了多囊卵巢综合征和非多囊卵巢综合征对照妇女的IVF结果相当。对这些患者TLM数据的分析显示,没有证据表明多囊卵巢综合征对接受试管婴儿周期的妇女的胚胎发育率有负面影响。
{"title":"Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos.","authors":"Gilad Karavani, Shira Shapira-Nass, Natali Schachter-Safrai, Tal Imbar, Assaf Ben-Meir","doi":"10.1016/j.xfss.2025.01.003","DOIUrl":"10.1016/j.xfss.2025.01.003","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>A retrospective case-control study conducted in a university-affiliated in vitro fertilization (IVF) unit.</p><p><strong>Patients: </strong>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.</p><p><strong>Exposure: </strong>Not applicable.</p><p><strong>Main outcome measures: </strong>Embryo development morphokinetic parameters in women with and without PCOS undergoing IVF treatments.</p><p><strong>Results: </strong>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 >75th percentile.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","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}
引用次数: 0
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