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 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.

Identification of a complex population of chromatin-associated proteins in the European sea bass (Dicentrarchus labrax) sperm

“…Finally, it is also worth pointing that the European sea bass sperm contains proteins which are related to oxidative stress and redox signaling during development, such as the Thioredoxin-dependent peroxide mitochondrial precursor (PRDX3), or the Peroxiredoxin 5 protein (PRDX5), which has been reported to have a role in sperm function and male fertility (Buckman et al 2013;Tirmarche et al 2016;Ryu et al 2017).…”

Spermatozoa micro ribonucleic acid–34c level is correlated with intracytoplasmic sperm injection outcomes

“…Several sperm and semen parameters, including sperm DNA (deoxyribonucleic acid) integrity (31), sperm head vacuolization (32), and spermatid-specific thioredoxin-3 (33), have been reported to be predictive of pregnancy after ICSI treatment. In our study, the levels of miR-34b and miR-34c were significantly higher in the pregnancy group compared with the nonpregnancy group, suggesting that paternal miRNA effects could be involved in low rates of implantation.…”

The Enzymatic Antioxidant System of Human Spermatozoa

“…SPTRX is associated with the Golgi and the perinuclear region in spermatids and it was found only in abnormal human spermatozoa from infertile men [140], suggesting an incomplete spermiogenesis with retention of residual bodies and cytoplasmic droplets.…”