Correction: Semen Levels of Spermatid-Specific Thioredoxin-3 Correlate with Pregnancy Rates in ART Couples

Abstract

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 twopronuclear 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.

Comprehensive Flow-Cytometric Quality Assessment of Ram Sperm Intended for Gene Banking Using Standard and Novel Fertility Biomarkers

“…On the contrary, mRNA expression of SPTRX-3 in ram testis was again confirmed by PCR analysis ( Appendix A ; Figure A1 ), thus indicating that SPTRX-3, as well as MKRN1 expression, should be assessed also in ram testis and defective spermatozoa using species-specific or cross-reactive antibodies. Moreover, it was demonstrated that higher levels of SPTRX-3 in semen correlate with male infertility [ 37 , 38 ]; therefore, SPTRX-3 might be an important quality indicator of individual ram semen intended for the preservation of genetic resources.…”

“…It has been observed to accumulate in the superfluous midpiece cytoplasm and nuclear vacuoles of defective human spermatozoa, or in the round testicular spermatids of other mammals. An increased content of SPTRX-3 positive spermatozoa was found in infertile males [ 37 , 38 ]. PAWP, post-acrosomal sheath WW-domain binding protein (known also as WBP2NL), is located in the post-acrosomal region of heads in normal spermatozoa and plays an important role during fertilization in the oocyte activation.…”