{"id":252,"title":"Circular RNA-NLRP3 Crosstalk in Reproductive Biology: A Critical Appraisal of Direct Evidence and Testable Hypotheses","title_zh":"环状RNA与NLRP3在生殖生物学中的交互作用：对直接证据与可检验假说的批判性评估","url":"https://pubmed.ncbi.nlm.nih.gov/42977869","doi":"10.1007/s43032-026-02239-9","pmid":"42977869","journal":"Reprod Sci","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Hsu CY","Abed HS","Ahmad I","Kareem AK","Abdulhussein NA","Alwan AMR","Singh A","Sunori SK","J BJ","Ray S"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":3.0,"hits":["granulosa","oocytes","ovarian"]},{"slug":"endometrium","score":3.0,"hits":["endometrial receptivity","placental","trophoblast"]},{"slug":"early-embryo","score":2.0,"hits":["blastocysts","zygotes"]},{"slug":"male","score":2.0,"hits":["seminal","sperm"]},{"slug":"ethics-policy","score":2.0,"hits":["regulation","regulatory"]},{"slug":"ivg-stem","score":1.0,"hits":["germ line"]},{"slug":"early-pregnancy","score":1.0,"hits":["preeclampsia"]},{"slug":"repro-aging","score":1.0,"hits":["ovarian aging"]}],"topic_score":3.0,"preference_score":5.0,"preference_labels":["可转化到 ART 实验室的发现"],"llm_score":72.0,"final_score":77.0,"score_dims":{"novelty":62,"rigor":82,"impact":62,"relevance":78,"translation":60},"recommend_reason":"该综述明确划分了circRNA-NLRP3轴在生殖领域的直接证据与推测性外推，为配子与胚胎研究提供了清晰的研究议程；有助于避免基于ceRNA预测的过度解读，对设计ART相关机制研究有方法学价值。","keywords":["环状RNA","NLRP3炎症小体","胚胎着床","ceRNA网络","颗粒细胞","生物标志物"],"selected":1,"story_id":145,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":3,"has_interpretation":false,"journal_key":"reprod-sci","journal_tier":"standard","journal_if":2.6,"is_mock":false,"summary_zh":"这是一篇发表于Reprod Sci的综述，系统梳理了环状RNA（circRNA）与NLRP3炎症小体在生殖生物学中的关系。作者将证据分为三类：存在直接功能证据的、仅有关联或生物信息学预测的，以及从非生殖系统外推的。直接证据仅有4例，涉及子痫前期滋养细胞、胎儿生长受限、颗粒细胞焦亡及妊娠期糖尿病模型；在精子、卵母细胞、受精卵、卵裂期胚胎、囊胚及男性生殖系中均未发现直接功能研究。作者强调，现有的共表达、宿主基因富集与ceRNA网络预测只能用于生成假设；精浆与母血circRNA虽具标志物潜力，但缺乏外部验证，相关干预手段仍处于临床前阶段。","summary":"Circular RNAs (circRNAs) are abundant and developmentally regulated in gonads, gametes, and preimplantation embryos, whereas NLRP3 inflammasome signaling has context-dependent roles in ovarian aging, spermatogenic stress, endometrial receptivity, implantation, and placental disease. Whether these two evidence streams constitute a functional regulatory axis in mammalian gametogenesis or early embryogenesis remains uncertain. In this regard, this review article aimed to identify direct reproductive mechanisms; reproductive functions without a demonstrated circRNA-NLRP3 bridge, association, or bioinformatic prediction; and mechanistic extrapolations from non-reproductive systems. Direct reproductive evidence was limited to four placental/trophoblast or granulosa-cell examples: circ_0001438/miR-942/NLRP3 signaling in preeclampsia-associated trophoblast models; circ_0081343-RBM8A regulation of NLRP3-linked pyroptosis in fetal-growth-restriction models; circ_0070987-associated pyroptosis in a dihydrotestosterone-treated granulosa-cell line; and hsa_circ_0003218 overexpression, which reduced NLRP3-pathway readouts in high-glucose HTR-8/SVneo trophoblasts in a gestational-diabetes study. No direct functional study was identified in mammalian sperm, oocytes, zygotes, cleavage-stage embryos, blastocysts, or the male germ line. Accordingly, circRNA detection, co-expression, host-gene enrichment, and predicted competing endogenous RNA networks should be regarded as hypothesis-generating rather than as proof of NLRP3 regulation. CircRNAs in seminal plasma and maternal blood show candidate biomarker potential, but external validation remains limited, and no combined reproductive circRNA-NLRP3 panel has been validated. Similarly, circRNA mimics, antisense approaches, circRNA-encoded peptides, extracellular vesicle (EVs) delivery, and combined circRNA/NLRP3 therapy remain preclinical or hypothetical in terms of reproduction. The most immediate priorities are cell-type- and stage-resolved perturbation studies, binding and rescue experiments, quantitative inflammasome readouts, reproductive safety assessment, and prospective biomarker validation.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}