Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice.
BACKGROUND
Successful oocyte in vitro maturation (IVM) would eliminate the need for hormonal stimulation used in assisted reproduction techniques. Unfortunately, oocytes matured in vitro have compromised developmental competence possibly due to disrupted oocyte-cumulus communication resulting from inappropriate levels of oocyte-secreted factors such as growth differentiation factor 9 (GDF9). Hence, the aim of this study was to investigate the effects of exogenous GDF9 during IVM of mouse oocytes on development and subsequent fetal viability.


METHODS
Cumulus-oocyte complexes from pregnant mare's serum gonadotrophin primed mice were cultured with or without 200 ng/ml exogenous recombinant GDF9, 50 mIU/ml FSH and 10 ng/ml epidermal growth factor (EGF). After 18 h, cumulus expansion was scored and oocytes were fertilized in vitro. Cleavage, blastocyst development, blastocyst total, inner cell mass (ICM) and trophectoderm cell numbers were assessed. Viability of embryos was assessed by transfer to recipient females and pregnancy outcome determined at day 15.


RESULTS
Oocytes matured with exogenous GDF9 in the presence of FSH and EGF had higher rates of development, percentage of hatching blastocyst and blastocyst total and ICM cell numbers (all P < 0.05). Although implantation rate and fetal and placental weights were not affected, the number of viable fetuses at day 15 was increased with exogenous GDF9.


CONCLUSIONS
Exogenous GDF9 during IVM improved embryo development and fetal viability and provides a promising approach for human IVM.
Yeo
Christine X
CX
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Medical School, Adelaide, South Australia 5005, Australia.
Gilchrist
Robert B
RB
Thompson
Jeremy G
JG
Lane
Michelle
M
D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology; D053624:Blastocyst Inner Cell Mass / Q000166:cytology; D055430:Bone Morphogenetic Protein 15; D002452:Cell Count; D048430:Cell Shape; D002478:Cells, Cultured; D003470:Culture Media; D054885:Cumulus Cells / Q000166:cytology / Q000502:physiology; D004357:Drug Synergism; D047108:Embryonic Development / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005307:Fertilization in Vitro; D005328:Fetal Viability / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000502:physiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011994:Recombinant Proteins / Q000494:pharmacology
C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D003470:Culture Media; C525897:GDF9 protein, human; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D005640:Follicle Stimulating Hormone