Mol. Hum. Reprod. Advance Access originally published online on January 19, 2008
Molecular Human Reproduction 2008 14(2):75-83; doi:10.1093/molehr/gam092
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Follicular growth and oocyte competence in the in vitro cultured mouse follicle: effects of gonadotrophins and steroids
1Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK 2Centre for Reproductive Biology, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4JT, UK
3 Correspondence address. Tel: +44-131-650-3267; Fax: +44-131-651-1706; E-mail: norah.spears{at}ed.ac.uk
Although there have been extensive studies on the effects of gonadotrophins and steroids on follicular development, less is known as to the effects these hormones have on the acquisition of oocyte developmental competence. This study investigates the effect of altering the gonadotrophin or steroidal environment on follicular development and on oocyte viability and DNA methylation. Oocytes were obtained from pre-ovulatory follicles after individual follicle culture from the pre-antral stage; gonadotrophin or steroid levels were manipulated during the culture period. Oocytes obtained from follicles grown in gonadotrophin free conditions were able to fertilize and develop to the blastocyst stage despite their impaired follicle development. There was no effect of luteinizing hormone or steroids on follicular growth. Altering the steroidal environment did, however, affect oocyte development. The oocytes of follicles exposed to high estrogen levels had lower fertilization rates, regardless of the presence or absence of high androgen levels. The combined presence of high levels of both steroids altered the level of global methylation. This study demonstrates that gonadotrophins and steroids influence the acquisition of developmental competence of the oocyte and suggests that optimal steroid exposure during follicle development is required for the oocyte to mature correctly.
Key words: DNA methylation/gonadotrophins/oocyte competence/steroids
Joint First Authors. 4 Present address: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Submitted on August 6, 2007; resubmitted on September 21, 2007; accepted on September 27, 2007.