C-C motif chemokine receptor 2 (CCR2) as a novel intermediate in the ovulatory cascade

PELUFFO, MC

Mar del Plata

Congreso; Reunión anual de Sociedades Biocientíficas; 2019

SAIC junto a otras sociedades

Shortly before ovulation the LH surge induces processes critical for fertility, including cumulus-oocyte expansion (C-OE) and resumption of meiosis. Since the molecular mechanisms responsible for initiating such complex processes are not fully understood, we hypothesized that interactions between chemokines and the chemokine receptor CCR2 have a direct effect promoting C-OE and/or oocyte maturation. To test this hypothesis, two separate novel feline culture systems were established in our laboratory. Studies were designed to a) evaluate the mRNA expression of CCR2 and its chemokine ligands, within the cumulus oocyte complex (COC) and follicle wall after a LH stimulus in cultured feline antral follicles; b) examine the direct effects of exogenous recombinant MCP1 (monocyte chemoattractant protein-1) on mRNA expression of key periovulatory genes in the COC, using a feline COC culture system; and c) determine whether inhibition of CCR2 signaling in the COC interferes with the expression of periovulatory genes and/or oocyte maturation. Results demonstrated mRNA expression of CCR2 receptor and its ligands within the feline COC and follicle wall, and a significant increase in CCR2 mRNA by LH within the COC. MCP1 treatment promoted a significant increase in mRNA levels of key periovulatory genes within the COC. Interestingly, a highly selective CCR2 antagonist significantly affected the stimulation of periovulatory genes induced by either gonadotropins, amphiregulin or prostaglandin E2. In summary, this is the first report in any species, describing a direct effect of MCP1 within the COC. More importantly, the stimulation of periovulatory genes occurs, at least in part, through the CCR2/MCP1 pathway, suggesting CCR2 receptor as a novel mediator of the ovulatory cascade. A better understanding of this novel role of CCR2 could eventually aid in the diagnosis or treatment of infertility; otherwise, this may help identifying novel targets for non-hormonal contraception.