{"id":38,"title":"Sperm phospholipase C signaling via PLCζ1 and PLCδ4 is essential for Ca2+ oscillations and fertility in mice","title_zh":"精子PLCζ1与PLCδ4协同驱动受精钙振荡：双基因敲除小鼠不育研究","url":"https://pubmed.ncbi.nlm.nih.gov/42993797","doi":"10.1371/journal.pbio.3004098","pmid":"42993797","journal":"PLoS Biol","kind":"paper","lang":"en","published_at":"2026-11-06T00:00:00+00:00","fetched_at":"2026-11-08T03:43:52+00:00","authors":["Gupta N","Zhang L","Akizawa H","Gervasi MG","Tourzani DA","Visconti PE","Romarowski A","Buffone M","Cui W","Fissore RA"],"primary_topic":"male","topics":[{"slug":"male","score":6.0,"hits":["acrosome","male infertility","sperm"]},{"slug":"art-clinical","score":4.0,"hits":["assisted reproductive","infertility","subfertility","trigger"]},{"slug":"contraception-health","score":1.0,"hits":["contraceptive"]},{"slug":"ethics-policy","score":1.0,"hits":["crispr"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":86.0,"final_score":86.0,"score_dims":{"novelty":88,"rigor":88,"impact":82,"relevance":90,"translation":72},"recommend_reason":"首次用双敲除体内模型明确PLCδ4是受精钙振荡的代偿因子，补全了精子PLC系统的协同机制，对男性不育机制、ART受精失败评估与避孕靶点均有参考价值。","keywords":["PLCζ1","PLCδ4","钙振荡","卵母细胞激活","男性不育","基因敲除小鼠"],"selected":1,"story_id":38,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-art","source_name":"PubMed · 辅助生殖临床","source_tier":1,"mention_count":2,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"本研究利用CRISPR/Cas9构建Plcδ4单敲除与PLCζ1/PLCδ4双敲除小鼠，检验精子磷脂酶C在受精钙振荡中的分工。结果显示，Plcδ4缺失精子诱发的钙振荡减弱且延迟，受精率显著下降；PLCζ1缺失精子中PLCδ4上调并在顶体反应后保留。双敲除雄鼠不育，其精子完全不能诱发钙振荡，残余钙升高不足以激活卵母细胞。结论认为，PLCζ1是主要振荡源，PLCδ4是代偿因子，二者协同构成多组分PLC系统以保障稳健受精，并提示哺乳动物受精钙信号的分子分化。","summary":"Fertilization-induced calcium (Ca2+) oscillations are essential for egg activation and embryonic development in mammals. The sperm-specific phospholipase C isoform, PLCζ1, is the primary trigger of these oscillations. Functional and clinical studies have linked mutations or reduced expression of PLCζ1 to male infertility. However, whether PLCζ1 alone accounts for Ca2+ release at fertilization in all mammals remains uncertain. Male mice lacking Plcζ1 exhibit subfertility and reduced litter sizes; their sperm induce delayed, low-frequency Ca2+ oscillations, indicating a compensatory mechanism. Notably, mouse sperm express high levels of PLCδ4, essential for completing the acrosome reaction (AR). In Plcζ1-null sperm, PLCδ4 is upregulated and retained post-AR. These observations suggest a secondary functional role for PLCδ4. Using CRISPR/Cas9 genome editing, we generated Plcδ4 knockout (KO) mice. Plcδ4-null sperm trigger attenuated, delayed Ca2+ oscillations and significantly reduced fertilization rates, indicating that PLCδ4 contributes to but does not independently drive Ca2+ signaling. We therefore generated a Double Knockout (DKO) mouse line lacking both sperm-enriched PLCs. DKO males were sterile, with sperm failing to induce Ca2+ oscillations, and the isolated residual Ca2+ rise was insufficient to activate eggs. These findings reveal that PLCζ1, the primary oscillator, and PLCδ4, a compensatory factor, work cooperatively within a complex, multi-component PLC system that ensures robust fertilization. This work reveals molecular specialization among mammals in initiating the fertilization Ca2+ signals. It has implications for understanding male infertility, improving assisted reproductive technologies, and developing contraceptive strategies.","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}}