CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Chemokines and Their Potential Application for New Female Contraceptive Development
Autor/es:
PELUFFO, MARINA C.
Reunión:
Simposio; SSR Solving Challenges in Contraceptive Discovery and Innovation; 2020
Institución organizadora:
Society for the Study of Reproduction
Resumen:
INVITED SPEAKERExpression of immune function genes within follicle cells has been reported in ovaries from many species. Interestingly, different chemokine receptors were shown to be expressed in the granulosa and theca bovine cells, suggesting an autocrine/paracrine role of chemokines in these two cell types. Cumulus oocyte complexes (COCs) in mice, cattle, and horses express the chemokine receptor CXCR4, and the LH surge increases its mRNA and protein levels in equine and bovine follicles. Limited published studies and our laboratory findings support a novel role for chemokines in regulating events necessary for periovulatory events, such as cumulus-oocyte expansion (C-OE) and oocyte maturation. Chiefly, prostaglandin E2 (PGE2) actions mediated through the PGE2 receptor subtype 2 (PTGER2), which are critical for C-OE and fertility in rodents, were shown to be mediated through certain chemokines. Rodent studies suggest that chemokine signaling regulates the assembly of the cumulus extracellular matrix and thus fertilization. Our results from domestic cats and rhesus macaques demonstrated that the chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 are expressed in the oocyte and cumulus cells of COCs from antral and preovulatory follicles. Interestingly, our laboratory has recently shown a direct effect of the MCP1/CCR2 system within the feline COC, by increasing the mRNA levels of key genes involved in the ovulatory cascade in vitro. Recombinant MCP1 also had a significant effect on spontaneous oocyte maturation (but not gonadotrophin-induced meiosis), increasing the percentage of MII stage oocytes in comparison to the control in vitro. Moreover, we have reported the modulation of several key ovulatory genes by a highly selective CCR2 antagonist (RS 504393). In this regard, RS 504393 was able to decrease the level of mRNA encoding critical periovulatory genes (AREG, HAS2, TNFAIP6, and PTX3) induced by gonadotropins, amphiregulin (AREG), or PGE2 within the feline COC. Therefore, these findings suggest CCR2 as a novel mediator of some actions of the mid-cycle gonadotrophin surge. Thus, a better understanding of the molecular and cellular processes triggered by CCR2 activation within the COC could aid to identify novel targets for a non-hormonal form of contraception.