ERp57 is a potential biomarker for human fertilization capability.
Human infertility is a growing concern and while many assisted reproductive technologies exist, their success rates are low. Thus, developing tests, possibly by assessing proteins involved in fertilization, that could predict the outcome of these technologies is of great significance. To identify candidate proteins, we used two-dimensional polyacrylamide gel electrophoresis and MALDI-TOF techniques and detected the ERp57 protein from human testis protein profile. Immunohistochemistry showed that ERp57 was mostly located in spermatogenic cell cytoplasm from spermatocytes to the spermatozoa phases and in Leydig cells of human testes; it was also present at low levels in Sertoli cells. ERp57 was evident in human spermatozoa, primarily in the acrosome and tail; moreover, it appeared to translocate to the equatorial segment after the acrosome reaction. During sperm capacitation, the ERp57 protein underwent post-translational modification. Blocking ERp57 with antibodies significantly inhibited human sperm from penetrating zona-free hamster oocytes in a dose-dependent manner. Finally, expression levels of ERp57 were associated with fertility; they were decreased dramatically in IVF patients with low fertilization rates compared with those with high rates or to fertile sperm donors. Taken together, these results show that ERp57 is a component of human sperm acrosome proteins, which play a critical role in gamete fusion. Furthermore, ERp57 could be a novel phenotype marker for male infertility and has the potential to be used to assess sperm selection for IVF.
Zhang
Jingjing
J
Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
Wu
Jindao
J
Huo
Ran
R
Mao
Yingzi
Y
Lu
Ying
Y
Guo
Xuejiang
X
Liu
Jiayin
J
Zhou
Zuomin
Z
Huang
Xiaoyan
X
Sha
Jiahao
J
D020101:Acrosome Reaction / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D006224:Cricetinae; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005298:Fertility / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009865:Oocytes / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism* / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013075:Sperm Capacitation / Q000502:physiology*; D013084:Sperm-Ovum Interactions / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology; D013737:Testis / Q000378:metabolism
D015415:Biomarkers; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human