Laboratorio de InmunoFisiología, Grupo Fisiopatología de la mujer, del embarazo, parto y puerperio, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Servicio de Ginecología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Hum Reprod. 2020 Nov 1;35(11):2567-2578. doi: 10.1093/humrep/deaa198.
What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm?
We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs).
Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis.
STUDY DESIGN, SIZE, DURATION: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA).
We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact.
N/A.
LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown.
Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility.
STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.
阴道多形核(PMN)精子杀伤机制是什么,以减少多余的精子?
我们表明,PMN 通过依赖于吞噬作用的杀精子活性非常有效地杀死精子,而这种活性与中性粒细胞胞外陷阱(NETs)无关。
吞噬作用已被描述为免疫细胞之间具有调节目的的主动膜交换。最近,吞噬作用已被报道为 PMN 用来杀死肿瘤细胞或阴道毛滴虫的一种机制。
研究设计、大小、持续时间:我们使用体内小鼠模型和人离体精子和 PMN 来研究 PMN-精子的早期反应。
参与者/材料、设置、方法:我们建立了一个活/死精子检测系统,在 PMN 的存在下,通过共聚焦显微镜、流式细胞术和计算机辅助精子分析(SCA)来研究体内和体外 PMN-精子的杀精子活性。
我们揭示了 PMN 通过一种不依赖于 NETs、依赖于接触和依赖于丝氨酸蛋白酶的吞噬作用机制,非常有效地杀死精子。PMN“咬住”精子,并在接触后迅速降低精子的运动能力(在 5 分钟内)和活力(在 20 分钟内)。
无。
局限性、谨慎的原因:这项研究是在使用鼠模型和健康的人血 PMN 进行的;它是否与人类阴道 PMN 或不孕病例有关尚不清楚。
阴道 PMN 通过吞噬作用攻击并固定阴道中的多余精子,因为精子是外源性的,可能携带病原体。此外,这种精子调节机制对粘膜的影响较小,可以避免过度的炎症反应,从而导致粘膜损伤或不孕。
研究资金/竞争利益:这项工作部分得到了经济和竞争力部 ISCIII-FIS 拨款、PI16/00050 和 PI19/00078 的支持,由欧洲委员会的欧洲区域发展基金(FEDER)共同资助,“欧洲的一种方式”和 IiSGM 内部拨款 II-PI-MRC-2017。M.R. 持有 Miguel Servet II 合同(CPII14/00009)。M.C.L. 持有 IiSGM 内部合同。没有竞争利益。