The chemokine SDF-1/CXCL12 contributes to T lymphocyte recruitment in human pre-ovulatory follicles and coordinates with lymphocytes to increase granulosa cell survival and embryo quality.
We investigated the production and the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in pre-ovulatory follicles of women undergoing in vitro fertilization. We detected CXCL12 and its receptor CXCR4 by flow cytometry, western blotting and RT-PCR. We tested cell migration in Transwell experiments. We measured apoptosis using delta psi m-sensitive fluorescent probe DiOC6(3) and we screened apoptosis-related gene expression with macro-arrays. Granulosa cells from follicular aspirates produce CXCL12 that contributes to T lymphocytes recruitment. CXCL12 reduces early apoptosis of granulosa cells. This effect is accompanied by a shift of bcl2/bax ratio, and decreased expression of p53-targeted genes (pig7, pig8, p21, gadd45). Removal of lymphocytes disables CXCL12-mediated anti-apoptotic effect on granulosa cells. Anti-apoptotic activity of CXCL12 is positively correlated to high quality of embryos. In conclusion, CXCL12 is locally produced by luteinizing granulosa cells. It specifically contributes to T lymphocytes recruitment and coordinates with local lymphocytes to increase granulosa cell survival and embryo quality.
Kryczek
Ilona
I
INSERM Unité 131 Cytokines et Immunorégulation, Institut Paris-Sud Sur les Cytokines, IFR 13, rue des Carnets, Clamart, France.
Frydman
Nelly
N
Gaudin
Françoise
F
Krzysiek
Roman
R
Fanchin
Renato
R
Emilie
Dominique
D
Chouaib
Salem
S
Zou
Weiping
W
Machelon
Véronique
V
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology*; D004622:Embryo, Mammalian / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006107:Granulosa Cells / Q000276:immunology*; D006801:Humans; D010060:Ovulation / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4