A differential cytokine expression profile is induced by highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone in a pre- and postovulatory mouse follicle culture model.
OBJECTIVE
To compare the differential effects of highly purified (HP) hMG or recombinant FSH (rFSH) on cytokine expression before and after ovulation in an in vitro mouse ovarian follicle model.


METHODS
A prospective laboratory in vitro study.


METHODS
A university-based reproductive biology laboratory. MATERIAL(S): Mechanically isolated mouse preantral follicles from 14-day-old prepubertal mouse ovaries (F1 hybrids: C57BL/6JxCBA/ca).


METHODS
Randomly distributed mouse early preantral follicles were exposed to two hyperstimulation conditions with either HP-hMG or rFSH. An ovulatory stimulus was given using hCG/epidermal growth factor. Conditioned media from the two culture conditions were collected on the days before and after in vitro ovulation. Conditioned media were compared for their relative cytokine profile content as measured by a cytokine antibody array analysis.


METHODS
Relative concentrations of 62 cytokines in conditioned media before and after ovulation.


RESULTS
Statistically significant increase in the production of a number of cytokines was found after HP-hMG stimulation compared with rFSH: 14 and 24 pre- and post-rhCG, respectively. Cytokines with the largest significant difference (more than 5 times) before and after ovulation included thymus-expressed cytokine (TECK), sTNFRI, and SDF-1alpha. The cytokines that are most strongly related to oocyte and embryo quality and implantation and that have been related to oocyte yield and maturation were significantly higher with HP-hMG.


CONCLUSIONS
The significant differences in follicular cytokine production induced by HP-HMG and rFSH before and after in vitro ovulation might explain the difference in treatment outcome.
Ferring Pharmaceuticals A/S, Obstetrics and Gynecology, Clinical Research and Development, Copenhagen, Denmark.
Rebecca
R
Foster
Ingrid
I
Segers
David
D
Smart
Tom
T
Adriaenssens
Johan
J
Smitz
Joan-Carles
JC
Arce
Marc
M
Princivalle
D000818:Animals; D002478:Cells, Cultured; D003433:Crosses, Genetic; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006801:Humans; D008596:Menotropins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D006080:Ovarian Follicle / Q000187:drug effects* / Q000276:immunology; D010062:Ovulation Induction / Q000379:methods*; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D017077:Culture Media, Conditioned; D016207:Cytokines; D005300:Fertility Agents, Female; D011994:Recombinant Proteins; D008596:Menotropins; D005640:Follicle Stimulating Hormone