학술논문

Spermatid-Specific Thioredoxin 3 (SPTRX3) Is a Biomarker of Human Male Infertility with Predictive Value for Decision Making in Infertility Treatment.
Document Type
Article
Source
Biology of Reproduction; May 2008, Vol. 78 Issue: 1, Number 1 Supplement 1 p56-56, 1p
Subject
Language
ISSN
00063363; 15297268
Abstract
Spermatid specific thioredoxin-3 protein (SPTRX-3) accumulates in the superfluous cytoplasm of defective human spermatozoa. We investigated the relationship between SPTRX3 levels and male infertility in men from 239 couples undergoing IVF or ICSI treatment. Sperm content of SPTRX3 was evaluated by flow cytometry, fluorescence microscopy, western blotting, and a novel ImageStream technology combining flow cytometry with high throughput cell imaging. Extremely high sperm SPTRX3 levels (>15% SPTRX3-positive sperm) were found in 51 % of male infertility patients (n=72), but also in 20% of men from couples diagnosed with idiopathic infertility (n=61) and in 14% of men from couples diagnosed with female infertility (n=85). Men with >15% SPTRX3-positive sperm had a significantly reduced chance of impregnating their partners by ICSI or IVF (16.7% pregnant couples with >15% SPTRX-positive sperm vs. 43.8% pregnant with <5% SPTRX3-positive sperm). SPTRX3-levels were significantly lower in couples treated by IVF than in couples that required treatment by ICSI. High sperm SPTRX3 compounded female infertility in couples diagnosed with combined male and female infertility (n=21), in which the % of SPTRX3-positive cells was increased by 25% in couples that failed to achieve pregnancy. High SPTRX3 content had a profound effect on pregnancy rates in the subgroup of women over 35 years of age (n=99), wherein the pregnancy rate was 40% when SPTRX3 levels were below 5%, but only 17.6% when the SPTRX3 levels of male partners were above 10% positive cells. Image Stream confirmed that the SPTRX-3 containing cells were spermatozoa with a variety of morphological defects. Flow cytometric SPTRX3 values correlated positively with light microscopic SPTRX3 evaluation in a subset of 150 patients evaluated by both methods. The SPTRX3- based assays thus provide an unbiased, objective diagnosis of male infertility relevant to decision making in ART. Supported by the F21C Program of the UM.