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Hum. Reprod. Advance Access published online on August 27, 2004
Human Reproduction, doi:10.1093/humrep/deh436
© 2004 by European Society of Human Reproduction and Embryology
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Received March 22, 2004
Accepted July 6, 2004

Article

A synthetic analogue of meiosis-activating sterol (FF-MAS) is a potent agonist promoting meiotic maturation and preimplantation development of mouse oocytes maturing in vitro

C. L. Marín Bivens 1, B. Lindenthal 2, M.J. O'Brien 1, K. Wigglesworth 1, T. Blume 2, C. Grøndahl 3, J. J. Eppig 1*

1 The Jackson Laboratory, Bar Harbor, Maine, USA
2 Schering AG, Research Laboratories, D-13342 Berlin, Germany
3 Novo Nordisk A/S, Discovery & Development, Novo Allé, DK-2880, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: jje{at}jax.org.


  Abstract

BACKGROUND: Follicular fluid-meiosis-activating sterol (FF-MAS) is a factor present in the pre-ovulatory follicle during the time of oocyte maturation. In mouse oocytes maturing in vitro, FF-MAS promotes the completion of meiotic maturation to metaphase II (MII) and improves competence to complete the 2-cell stage to blastocyst transition. We produced analogues of FF-MAS and selected three on the basis of potency to promote the resumption of meiosis by mouse oocytes maintained in meiotic arrest by hypoxanthine. The objective of this study was to determine whether these FF-MAS analogues also affect the quality of oocytes maturing in vitro with respect to the completion of meiotic maturation and augmenting the frequency of development to the blastocyst stage after fertilization in vitro. METHODS: Cumulus cell-enclosed oocytes were isolated from the small antral follicles of 18 or 20 day post-natal mice. These oocytes normally have a reduced competence to complete meiotic maturation and preimplantation embryo development. Oocytes were isolated at the germinal vesicle stage and matured in vitro using media supplemented with 0.1% ethanol, 1 µmol/l FF-MAS, or 0.1-10 µmol/l FF-MAS analogues ZK255884 (884), ZK255933 (933) and ZK255991 (991). Oocytes that progressed to MII were fertilized in vitro and the percentage developing to the 2-cell and blastocyst stages was determined. RESULTS: At 1 µmol/l, 991 and 933 increased the portion of oocytes progressing to MII, whereas the lowest dose of 991 and 884 was ineffective. Treatment of maturing oocytes with either 0.1 or 1 µmol/l 933 dramatically increased oocyte competence to complete preimplantation development. CONCLUSIONS: The synthetic analogue of FF-MAS, ZK255933, is a potent agonist that improves the quality of mouse oocytes matured in vitro. This compound may therefore have therapeutic value for treatment of oocytes from women undergoing therapy for infertility owing to poor oocyte quality.

Keywords: fertilization; follicular fluid-meiosis-activating sterol (FF-MAS); oocyte maturation; meiosis; preimplantation development.
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