Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice

Rhonda K. Trousdale, Bo Yu, Susan V. Pollak, Nabil Husami, Andrea Vidali, Joyce W. Lustbader

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalFertility and Sterility
Volume91
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Human Follicle Stimulating Hormone
Follicle Stimulating Hormone
Fertility
Equine Gonadotropins
Ovulation
Eggs
Litter Size
Ovulation Induction
Embryonic Development
Embryonic Structures
Carbohydrates

Keywords

  • Fertility
  • glycoengineering
  • hyperglycosylated FSH
  • N-linked glycosylation
  • O-linked glycosylation
  • ovary

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice. / Trousdale, Rhonda K.; Yu, Bo; Pollak, Susan V.; Husami, Nabil; Vidali, Andrea; Lustbader, Joyce W.

In: Fertility and Sterility, Vol. 91, No. 1, 01.2009, p. 265-270.

Research output: Contribution to journalArticle

Trousdale, Rhonda K. ; Yu, Bo ; Pollak, Susan V. ; Husami, Nabil ; Vidali, Andrea ; Lustbader, Joyce W. / Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice. In: Fertility and Sterility. 2009 ; Vol. 91, No. 1. pp. 265-270.
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abstract = "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.",
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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.

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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.

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KW - glycoengineering

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KW - N-linked glycosylation

KW - O-linked glycosylation

KW - ovary

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