A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels

• Published in: Journal of assisted reproduction and genetics 2020-02, Vol.37 (2), p.405-416
• Main Authors: Noël, Laure, Fransolet, Maïté, Jacobs, Nathalie, Foidart, Jean-Michel, Nisolle, Michelle, Munaut, Carine
• Format: Article
• Language: English
• Subjects: Biomarkers - blood; Chemokines; Coculture Techniques; Colony-stimulating factor; Culture Media, Conditioned - pharmacology; Cytokines; Embryo Implantation - genetics; Embryos; Female; Fertilization in Vitro; Follicles; Follicular Fluid - metabolism; G-CSF; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - genetics; Granulocyte Colony-Stimulating Factor - metabolism; Granulocytes; Granulosa cells; Granulosa Cells - metabolism; Gynecology; Human Genetics; Human health sciences; Humans; In vitro fertilization; Leukocytes; Leukocytes (granulocytic); Leukocytes - metabolism; Medicine; Medicine & Public Health; Menstrual cycle; Médecine de la reproduction (Gynécologie, andrologie, obstétrique); Oocytes - growth & development; Oocytes - metabolism; Ovarian Follicle - metabolism; Ovary; Ovulation; Paracrine signalling; Reproductive Medicine; Reproductive medicine (gynecology, andrology, obstetrics); Reproductive Physiology and Disease; Sciences de la santé humaine
• ISSN: 1058-0468; 1573-7330; 1573-7330
• DOI: 10.1007/s10815-020-01692-y

Objective Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly understood. Our study aimed to investigate the mechanisms and cells responsible for G-CSF production in the preovulatory follicle. Design Laboratory research study. Setting Single-center study. Interventions Granulosa cells and leukocytes were isolated from the follicular fluids (FF) or the blood of women undergoing IVF and from the blood of a control group of women with spontaneous ovulatory cycles to perform cocultures. Main outcome measure G-CSF-secreted protein was quantified in the conditioned media of cocultures. Results G-CSF secretion was considerably increased in cocultures of granulosa cells and leukocytes. This effect was maximal when leukocytes were isolated from the blood of women in the late follicular phase of the menstrual cycle or from the FF of women undergoing IVF. The leukocyte population isolated from the FF samples of women undergoing IVF had a higher proportion of granulocytes than that isolated from the corresponding blood samples. Leukocytes induced the synthesis and secretion of G-CSF by granulosa cells. Among a range of other FF cytokines/chemokines, only growth-regulated oncogene alpha (GROα) was also increased. Conclusion The notable rise in G-CSF at the time of ovulation coincides with the accumulation of follicular granulocytes, which stimulate G-CSF production by granulosa cells via paracrine interactions. High follicular G-CSF concentrations may occur in follicles with optimal granulosa–leukocyte interactions, which could explain the increased implantation rate of embryos arising from these follicles.