Effects of urinary and recombinant gonadotrophins on gene expression profiles during the murine peri-implantation period.
BACKGROUND
Controlled ovarian stimulation (COS) with urinary gonadotrophins but not recombinant gonadotrophins, adversely affect the implantation process. In this study, we investigated the effects of urinary and recombinant gonadotrophins on gene expression profiles at implantation sites during the mouse peri-implantation period and the possible molecular mechanisms involved in the detrimental effects of urinary gonadotrophins using microarray technology.


METHODS
Adult female CD1 mice were treated with (i) urinary human FSH (hFSH) and urinary HCG, (ii) recombinant hFSH and recombinant human LH or (iii) saline. Gene expression profiling with GeneChip mouse genome 430 2.0 arrays, containing 45 101 probe sets, was performed using implantation sites on embryonic day 5. Data were statistically analysed using Significance Analysis of Microarrays. Ten genes from the microarray analysis were selected for validation using quantitative RT-PCR (qRT-PCR). A parallel group of pregnant mice was allowed to give birth to study the effect of gonadotrophins on resorption.


RESULTS
Urinary gonadotrophins differentially up-regulated the expression of 30 genes, increased resorption and reduced litter size, whereas recombinant gonadotrophins did not. Nine of the 10 genes were confirmed by qRT-PCR.


CONCLUSIONS
Urinary gonadotrophins, but not recombinant gonadotrophins, exerted differential effects on gene expression during the murine peri-implantation period. These findings might contribute to improve protocols for COS, leading to higher successful pregnancy rates.
Sibug
R M
RM
Division of Medical Pharmacology, Leiden Amsterdam Center for Drug Research/Leiden University Medical Center, The Netherlands.
Datson
N
N
Tijssen
A M I
AM
Morsink
M
M
de Koning
J
J
de Kloet
E R
ER
Helmerhorst
F M
FM
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology* / Q000652:urine*; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D005640:Follicle Stimulating Hormone / Q000494:pharmacology* / Q000652:urine*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005802:Genes, MHC Class II / Q000502:physiology; D006062:Gonadotropins / Q000652:urine*; D006801:Humans; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010062:Ovulation Induction; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone