Semen levels of spermatid-specific thioredoxin-3 correlate with pregnancy rates in ART couples.

Semen levels of spermatid-specific thioredoxin-3 correlate with pregnancy rates in ART couples.
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DOI:
10.1371/journal.pone.0061000
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sutovsky P
Sutovsky P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Buckman C;Ozanon C;Qiu J;Sutovsky M;Carafa JA;Rawe VY;Manandhar G;Miranda-Vizuete A;Sutovsky P

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精子细胞特异性硫氧还蛋白-3(SPTRX3 或 TXNDC8)是硫氧还蛋白家族的睾丸/雄性生殖系特异性成员,在有缺陷的人类精子的多余细胞质中积累。我们假设精液中的 SPTRX3 水平反映了接受体外受精 (IVF) 或胞浆内单精子注射 (ICSI) 治疗的辅助生殖治疗 (ART) 夫妇的治疗结果。在不孕不育诊所接受 ART 的 239 对夫妇中,研究了 SPTRX3 与治疗结果之间的关系。通过流式细胞术和落射荧光显微镜评估精子的 SPTRX3 含量,并与临床精液分析参数以及胚胎发育和妊娠建立的数据相关。 51% 的男性不育患者 (n = 72)、20% 的不明原因特发性不孕夫妇的男性 (n = 61) 以及 14% 的先前诊断为女性不孕症的夫妇中的男性中发现高 SPTRX3 水平(>15% SPTRX3 阳性精子) (n = 85)。 SPTRX3 水平较高的夫妇产生的双原核受精卵较少,妊娠率也较低(SPTRX3 阳性精子 >15% 的孕妇为 19.2%,SPTRX3 阳性精子 <5% 的孕妇为 41.2%;单侧 p<0.05)。所有239对夫妇的平均怀孕率为25.1%。活产率为 19.2%,生下双胞胎的夫妇的平均 SPTRX3 水平最低。 SPTRX3 阳性精子超过 15%(ROC 分析确定的临界值)的男性通过 IVF 或 ICSI 生育孩子的机会减少近三分之二。 SPTRX3 阳性精子的百分比对 ART 后妊娠具有预测价值。梯度纯化和精子游上未能从准备 ART 的精液中去除所有 SPTRX3 阳性精子。总之,ART 夫妇的男性精液中 SPTRX3 含量升高与 IVF 或 ICSI 妊娠发生率降低相一致,因此将 SPTRX3 确定为反映 ART 结果的候选生物标志物。
Spermatid specific thioredoxin-3 (SPTRX3 or TXNDC8) is a testis/male germ line specific member of thioredoxin family that accumulates in the superfluous cytoplasm of defective human spermatozoa. We hypothesized that semen levels of SPTRX3 are reflective of treatment outcome in assisted reproductive therapy (ART) couples treated by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Relationship between SPTRX3 and treatment outcome was investigated in 239 couples undergoing ART at an infertility clinic. Sperm content of SPTRX3 was evaluated by flow cytometry and epifluorescence microscopy, and correlated with clinical semen analysis parameters, and data on embryo development and pregnancy establishment. High SPTRX3 levels (>15% SPTRX3-positive spermatozoa) were found in 51% of male infertility patients (n = 72), in 20% of men from couples with unexplained, idiopathic infertility (n = 61) and in 14% of men from couples previously diagnosed with female-only infertility (n = 85). Couples with high SPTRX3 produced fewer two-pronuclear zygotes and had a reduced pregnancy rate (19.2% pregnant with >15% SPTRX3-positive spermatozoa vs. 41.2% pregnant with <5% SPTRX3-positive sperm; one-sided p<0.05). The average pregnancy rate of all 239 couples was 25.1%. Live birth rate was 19.2% and lowest average SPTRX3 levels were found in couples that delivered twins. Men with >15% of SPTRX3-positive spermatozoa, a cutoff value established by ROC analysis, had their chance of fathering children by IVF or ICSI reduced by nearly two-thirds. The percentage of SPTRX3-positive spermatozoa had predictive value for pregnancy after ART. Gradient purification and sperm swim-up failed to remove all SPTRX3-positive spermatozoa from semen prepared for ART. In summary, the elevated semen content of SPTRX3 in men from ART couples coincided with reduced incidence of pregnancy by IVF or ICSI, identifying SPTRX3 as a candidate biomarker reflective of ART outcome.
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