Meseguer Marcos, de los Santos Maria J, Simón Carlos, Pellicer Antonio, Remohí José, Garrido Nicolás
Instituto Valenciano de Infertilidad Valencia, Universidad de Valencia, Valencia, Spain.
Fertil Steril. 2006 Nov;86(5):1376-85. doi: 10.1016/j.fertnstert.2006.03.053. Epub 2006 Sep 18.
To prospectively determine the impact of concrete components of the sperm oxidative glutathione stress system in terms of enzymatic activity and mitochondrial RNA (mRNA) expression on embryo quality and reproductive outcome. Human spermatozoa use the glutathione system to inactivate reactive oxygen metabolites, and there is a close correlation between some components of the glutathione system and male fertility. However, very few data are published regarding this system in sperm cells and its effect on fertilization ability and embryo development in human beings.
An oocyte-donation model, used to homogenize the female factor.
University-affiliated private IVF setting.
PATIENT(S): Semen samples from infertile males (n = 43) of couples undergoing oocyte-donation cycles (n = 43).
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Gene expression and activity of glutathione peroxidases (GPXs) 1 and 4, glutathione reductase, and intracellular glutathione (GSH) by fluorescent quantitative polymerase chain reaction and spectrophotometry, respectively.
RESULT(S): Fertilization rate, pronuclear number, asymmetry, and pronuclear body distribution were not correlated with any sperm glutathione parameters that were considered. When day 3 embryo parameters were evaluated, only GPX4 mRNA expression in sperm cells was statistically significantly lower when asymmetric embryos were observed. Also, worst embryo development and morphology on day 5 was statistically significantly correlated with lower sperm GPX1 activity (101.07 vs. 258.8 IU/mg protein). Glutathione system analysis in fresh sperm was not statistically significantly different in patients achieving pregnancy compared with those who not, and we did not find any correlation with implantation rate.
CONCLUSION(S): We have been able to correlate embryo morphology on day 3 with the sperm expression of GPX family members. The results indicate that sperm-derived mRNA may condition human embryo quality and persist even to blastocyst stage. The correlation of the sperm GPX family mRNA expression with embryo health appears quite promising for discovery of molecular causes of male infertility.
前瞻性地确定精子氧化型谷胱甘肽应激系统的具体组成部分在酶活性和线粒体RNA(mRNA)表达方面对胚胎质量和生殖结局的影响。人类精子利用谷胱甘肽系统使活性氧代谢产物失活,并且谷胱甘肽系统的某些组成部分与男性生育能力之间存在密切关联。然而,关于该系统在精子细胞中的情况及其对人类受精能力和胚胎发育的影响,发表的数据极少。
采用卵母细胞捐赠模型,以统一女性因素。
大学附属私立体外受精机构。
接受卵母细胞捐赠周期的不育男性(n = 43)的精液样本(n = 43)。
无。
分别通过荧光定量聚合酶链反应和分光光度法检测谷胱甘肽过氧化物酶(GPX)1和4、谷胱甘肽还原酶以及细胞内谷胱甘肽(GSH)的基因表达和活性。
受精率、原核数量、不对称性和原核体分布与所考虑的任何精子谷胱甘肽参数均无相关性。在评估第3天的胚胎参数时,仅当观察到不对称胚胎时,精子细胞中的GPX4 mRNA表达在统计学上显著较低。此外,第5天最差的胚胎发育和形态与较低的精子GPX1活性在统计学上显著相关(101.07对258.8 IU/mg蛋白质)。与未怀孕的患者相比,成功怀孕患者新鲜精子中的谷胱甘肽系统分析在统计学上无显著差异,并且我们未发现其与着床率有任何相关性。
我们已经能够将第3天的胚胎形态与GPX家族成员的精子表达相关联。结果表明,精子来源的mRNA可能影响人类胚胎质量,甚至持续到囊胚阶段。精子GPX家族mRNA表达与胚胎健康的相关性对于发现男性不育的分子原因似乎很有前景。