VIP treatment prevents embryo resorption modulating maternal macrophage efferocytosis and their activation profile in the CBAxDBA resorption prone model.

GALLINO L, CALO, HAUK V, FRACCAROLI L, GRASSO E, VERMEULEN M, PÉREZ LEIRÓS C AND RAMHORST R

Scientific Reports

NPG

Año: 2016 vol. 6 p. 18633 - 18643

Successful embryo implantation occurs followed by a local pro-inflammatory response subsequentlyshifted toward a tolerogenic one. VIP (vasoactive intestinal peptide) has embryotrofic, antiinflammatoryand tolerogenic effects. In this sense, we investigated whether the in vivo treatmentwith VIP contributes to an immunosuppressant local microenvironment associated with an improvedpregnancy outcome in the CBA/J × DBA/2 resorption prone model.Pregnancy induced the expressionof VIP, VPAC1 and VPAC2 in the uterus from CBA/J × DBA/2 mating females on day 8.5 of gestationcompared with non-pregnant mice. VIP treatment (2 nmol/mouse i.p.) on day 6.5 significantly increasedthe number of viable implantation sites and improved the asymmetric distribution of implantedembryos. This effect was accompanied by a decrease in RORγt and an increase in TGF-β and PPARγexpression at the implantation sites. Moreover, VIP modulated the maternal peritoneal macrophagesefferocytosis ability, tested using latex beads-FITC or apoptotic thymocytes, displaying an increasedfrequency of IL-10-producer F4/80 cells while did not modulate TNF-α and IL-12 secretion.Thepresent data suggest that VIP treatment increases the number of viable embryos associated with anincrease in the efferocytic ability of maternal macrophages which is related to an immunosuppressantmicroenvironment.