Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization.
A major challenge of assisted reproduction technologies (ARTs) is to mimic the natural environment required to sustain oocyte and embryo survival. Herein, we show that the ceramide-metabolizing enzyme, acid ceramidase (AC), is expressed in human cumulus cells and follicular fluid, essential components of this environment, and that the levels of this enzyme are positively correlated with the quality of human embryos formed in vitro. These observations led us to develop a new approach for oocyte and embryo culture that markedly improved the outcome of in vitro fertilization (IVF). The addition of recombinant AC (rAC) to human and mouse oocyte culture medium maintained their healthy morphology in vitro. Following fertilization, the number of mouse embryos formed in the presence of rAC also was improved (from approximately 40 to 88%), leading to approximately 5-fold more healthy births. To confirm these observations, immature bovine oocytes were matured in vitro and subjected to IVF in the presence of rAC. Significantly more high-grade blastocysts were formed, and the number of morphologically intact, hatched embryos was increased from approximately 24 to 70%. Overall, these data identify AC as an important component of the in vivo oocyte and embryo environment, and provide a novel technology for enhancing the outcome of assisted fertilization. Eliyahu, E., Shtraizent, N., Martinuzzi, K., Barritt, J., He, X., Wei, H., Chaubal, S., Copperman, A. B., Schuchman, E. H. Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization.
Eliyahu
Efrat
E
Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, 1425 Madison Ave., Rm. 14-20A, New York, NY 10029, USA.
Shtraizent
Nataly
N
Martinuzzi
Kurt
K
Barritt
Jason
J
He
Xingxuan
X
Wei
Hong
H
Chaubal
Sanjeev
S
Copperman
Alan B
AB
Schuchman
Edward H
EH
D055573:Acid Ceramidase / Q000494:pharmacology*; D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D002417:Cattle; D018929:Cell Culture Techniques; D054885:Cumulus Cells / Q000166:cytology*; D046149:Embryo Culture Techniques; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D009865:Oocytes / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D055573:Acid Ceramidase