Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

Abstract

Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ) technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39), which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

Influence of antifertility agents Dutasteride and Nifedipine on CatSper gene level in epididymis during sperm maturation in BALB/c mice

“…The results of present study showed no significant changes in final body and testis weights with significant decreases in the weights of the DHT-dependent tissues such as epididymis, seminal vesicle or VP of male BALB/c mice treated with DS compared to controls. Our results are in agreement with findings of Henderson et al (2004) and by Xie et al (2016) in male rats after treatment with DS. The slight reduction in body weights of NF-treated mice is in accordance with results of Lee et al (2006) in NF-treated ICR male mice.…”

“…Sperm functions such as count and motility are key indices of male fertility as these are prime markers in testicular spermatogenesis and epididymal sperm maturation. The significant decline in sperm count of caput and cauda epididymides of DS-and NF-treated mice in current study are in accordance with findings reported by Henderson and Robaire (2005) and by Xie et al (2016) in DS-treated rats. The reduced sperm count of cauda epididymis in NF-treated mice is in accordance with findings of Morakinyo et al (2009) in NF-treated rats.…”

“…Our results indicated that sperm motility of cauda epididymal spermatozoa was significantly reduced both by DS and NF in order of DS > NF. The results are in accordance with the results of Henderson & Robaire (2005) and Xie et al (2016) who reported significant decrease in the percentage of motile and progressively motile sperm from the cauda epididymis of DS-treated rats. Likewise, Morakinyo et al (2009) showed reduced sperm motility of cauda epididymal spermatozoa after NF treatment in rat.…”

“…The percentage of highly agglutinated, tailless, decapitated, angulated and broken spermatozoa was common in treated mice both with DS and NF. Our findings parallel recent reports of Henderson & Robaire (2005) and Xie et al (2016). It is interesting that male infertility of apparently healthy animals able to mate has, in some instances, been correlated with spermatozoa displaying angulated flagella when released from the epididymis.…”

Proteomic Analysis Reveals a New Benefit of Periodic Mechanical Stress on Chondrocytes

“…The peptide mixture was loaded onto a C18-reverse phase column (15 cm long, 75 µm inner diameter, RP-C18 3 µm, packed in-house) in buffer A (0.1% formic acid) and separated with a linear gradient of buffer B (80% ACN, 0.1% formic acid) at a flow rate of 250 nl/min controlled by IntelliFlow technology over 240 min. The peptides were eluted with a gradient of 0–55% buffer B for 220 min, 55%–100% buffer B for 8 min and held in 100% buffer B for 12 min [20]. For MS analysis, peptides were analyzed in positive ion mode.…”