Paternal contributors in recurrent pregnancy loss: Cues from comparative proteome profiling of seminal extracellular vesicles,Molecular Reproduction and Development

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Paternal contributors in recurrent pregnancy loss: Cues from comparative proteome profiling of seminal extracellular vesicles
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2020-12-20 , DOI: 10.1002/mrd.23445
Soumya R Jena _{1,

2} , Jasmine Nayak _{1,

2} , Sugandh Kumar ₃ , Sujata Kar ₄ , Anshuman Dixit ₃ , Luna Samanta _{1,

2}

Affiliation

Recent evidence entail paternal factors as plausible contributors in spontaneous recurrent pregnancy loss (RPL). Seminal extracellular vesicles secreted from cells of male reproductive tract carry regulatory proteins and RNAs. They are proposed to regulate sperm maturation and function while their fusion to endometrial stromal cells helps in decidualization. Nevertheless, the mechanism(s) involved in these processes are poorly understood. This study aims at elucidating the molecular basis of paternal contribution by comparative proteomics (label‐free LC‐MS/MS) of isolated seminal extracellular vesicles from fertile men and partners of patients with RPL (n = 21 per group). Bioinformatics analysis revealed the identified differentially expressed proteins to be involved in DNA replication, recombination and repair, gene expression, cellular assembly and organization, cell death, and survival. Major disease pathways affected were identified as developmental, hereditary, and immunological disorders. Of the three identified hub genes regulating the above disease pathways, two (HNRNPC and HNRNPU) are overexpressed while RUVBL1 is underexpressed along with over expression of HIST1H1C, DDX1, surmising defective chromatin packaging, and histone removal in spermatozoa resulting in improper expression in paternal genes thereby leading to abnormal embryo development. Besides, alteration in GSTP1 expression points oxidative predominance in RPL group. Differential expression of C3, C4a/C4b, CFB, and GDF 15 may be involved in altered maternal immune response to paternal antigens resulting in impaired decidualization.

中文翻译：

反复流产的父亲贡献者：来自精细胞外囊泡比较蛋白质组分析的线索

最近的证据表明，父亲因素可能是自发性复发性流产 (RPL) 的诱因。从男性生殖道细胞分泌的精细胞外囊泡携带调节蛋白和 RNA。它们被提议用于调节精子的成熟和功能，而它们与子宫内膜基质细胞的融合有助于蜕膜化。然而，对这些过程中涉及的机制知之甚少。本研究旨在通过比较蛋白质组学（无标记 LC-MS/MS）从可育男性和 RPL（n = 每组 21 个）。生物信息学分析显示，鉴定出的差异表达蛋白参与 DNA 复制、重组和修复、基因表达、细胞组装和组织、细胞死亡和存活。受影响的主要疾病途径被确定为发育、遗传和免疫障碍。在调节上述疾病途径的三个确定的枢纽基因中，两个（HNRNPC 和 HNRNPU）过度表达，而 RUVBL1 表达不足以及 HIST1H1C、DDX1 的过度表达，推测有缺陷的染色质包装和精子中的组蛋白去除导致父本基因的不当表达从而导致胚胎发育异常。此外，GSTP1 表达的改变表明 RPL 组中氧化占优势。C3、C4a/C4b、CFB、

更新日期：2021-01-28

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