Negative biomarker based male fertility evaluation: Sperm phenotypes associated with molecular-level anomalies.
Negative biomarker based male fertility evaluation: Sperm phenotypes associated with molecular-level anomalies.
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DOI：
10.4103/1008-682x.153847
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发表时间：
2015-07
影响因子：
2.9
通讯作者：
Oko R
中科院分区：
文献类型：
--
作者：
Sutovsky P;Aarabi M;Miranda-Vizuete A;Oko R
基于生物标记的精子分析提高了人类不育症的治疗效果并改善了牲畜的繁殖性能。基于阴性生物标志物的方法侧重于缺陷精子特有的蛋白质和配体，无论其形态表型如何，都适合通过流式细胞术（FC）进行分析。一个典型的例子是精子细胞特异性硫氧还蛋白 SPTRX3/TXNDC8，保留在有缺陷的人类精子的核液泡和多余细胞质中。精液 SPTRX3 含量高的不孕夫妇通过辅助生殖治疗 (ART) 受孕的可能性较小，并且更容易反复流产，而精液 SPTRX3 含量低的夫妇则与多次 ART 分娩有关。泛素是一种小的促进蛋白水解的共价翻译后蛋白修饰剂，存在于有缺陷的睾丸后精子的表面和受损的蛋白质聚集体（生精起源的聚集体）中。精液泛素含量与生育力和常规精液参数以及精子凝集素 LCA（小豆凝集素；揭示精子表面改变）和 PNA（花生凝集素；揭示顶体畸形或损伤）的结合呈负相关。顶体鞘 WWI 结构域结合蛋白 (PAWP) 与受精过程中卵母细胞的激活有关，在有缺陷的人类和动物精子中是异位的或缺失的。因此，PAWP 的 FC 参数与不孕夫妇的 ART 结果以及公牛的生育力相关。基于上述生物标志物的测定已被合并到多重 FC 精液筛选方案中，并且利用凝集素和泛素的表面表达来开发基于纳米颗粒的公牛精液纯化方法，并通过现场人工授精试验进行验证。这些进步与 FC 技术和基于基因组学/蛋白质组学的生物标志物发现的创新齐头并进。
Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery.