TY - JOUR
T1 - Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice
AU - Trousdale, Rhonda K.
AU - Yu, Bo
AU - Pollak, Susan V.
AU - Husami, Nabil
AU - Vidali, Andrea
AU - Lustbader, Joyce W.
PY - 2009/1
Y1 - 2009/1
N2 - Objective: To compare the efficacy of recombinant human FSH (rhFSH) with rhFSH with four additional O-linked carbohydrates (rhFSH-CTP), rhFSH with four additional N-linked carbohydrates (rhFSH-N4), and the current gold standard for rodent ovarian stimulation, pregnant mare serum gonadotropin (PMSG), on fertility parameters in mice. Design: Animal study. Setting: Academic research center. Animal(s): Adult C57Bl/6J female mice. Intervention(s): Ovarian stimulation with 5 IU of rhFSH, rhFSH-CTP, rhFSH-N4, or PMSG. Forty-six hours later, 5 IU of hCG was injected to promote ovulation and females were mated overnight. Main Outcome Measure(s): Eggs retrieved after ovulation, in vitro embryo development, delivery rate, and litter size. Result(s): The hyperglycosylated FSH analogs, rhFSH-CTP and rhFSH-N4, enhanced ovulation and embryo maturation significantly better than rhFSH. RhFSH-N4 produced more eggs (28.5 ± 1.9 per mouse) and embryos (17.8 ± 1.6) compared with rhFSH-CTP (18.3 ± 1.2 and 9.0 ± 1.0, respectively). Treatment with rhFSH, rhFSH-N4, and PMSG produced statistically equivalent delivery rates and litter sizes. The delivery rate was surprisingly lower with rhFSH-CTP (14%) compared with PMSG (33%). Conclusion(s): Compared with rhFSH, treatment with hyperglycosylated rhFSH-CTP and rhFSH-N4 led to superior rates of ovulated eggs and subsequent in vitro embryo development. RhFSH-N4 was equivalent to PMSG, while all of the fertility parameters studied were lower with rhFSH-CTP than with PMSG therapy.
AB - Objective: To compare the efficacy of recombinant human FSH (rhFSH) with rhFSH with four additional O-linked carbohydrates (rhFSH-CTP), rhFSH with four additional N-linked carbohydrates (rhFSH-N4), and the current gold standard for rodent ovarian stimulation, pregnant mare serum gonadotropin (PMSG), on fertility parameters in mice. Design: Animal study. Setting: Academic research center. Animal(s): Adult C57Bl/6J female mice. Intervention(s): Ovarian stimulation with 5 IU of rhFSH, rhFSH-CTP, rhFSH-N4, or PMSG. Forty-six hours later, 5 IU of hCG was injected to promote ovulation and females were mated overnight. Main Outcome Measure(s): Eggs retrieved after ovulation, in vitro embryo development, delivery rate, and litter size. Result(s): The hyperglycosylated FSH analogs, rhFSH-CTP and rhFSH-N4, enhanced ovulation and embryo maturation significantly better than rhFSH. RhFSH-N4 produced more eggs (28.5 ± 1.9 per mouse) and embryos (17.8 ± 1.6) compared with rhFSH-CTP (18.3 ± 1.2 and 9.0 ± 1.0, respectively). Treatment with rhFSH, rhFSH-N4, and PMSG produced statistically equivalent delivery rates and litter sizes. The delivery rate was surprisingly lower with rhFSH-CTP (14%) compared with PMSG (33%). Conclusion(s): Compared with rhFSH, treatment with hyperglycosylated rhFSH-CTP and rhFSH-N4 led to superior rates of ovulated eggs and subsequent in vitro embryo development. RhFSH-N4 was equivalent to PMSG, while all of the fertility parameters studied were lower with rhFSH-CTP than with PMSG therapy.
KW - Fertility
KW - N-linked glycosylation
KW - O-linked glycosylation
KW - glycoengineering
KW - hyperglycosylated FSH
KW - ovary
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U2 - 10.1016/j.fertnstert.2007.11.013
DO - 10.1016/j.fertnstert.2007.11.013
M3 - Article
C2 - 18249396
AN - SCOPUS:57849140300
SN - 0015-0282
VL - 91
SP - 265
EP - 270
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 1
ER -