Abstract
Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-α and IFN-γ expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations.
Highlights
Pregnancy has been considered a state of maternal immunological tolerance because the maternal immune system protects the semi-allogenic fetus during the implantation period
Previous findings from our group showed that the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro [16]. bvPLA2 directly binds to CD206, a mannose receptor expressed on dendritic cells, and modulates the secretion of PGE2, resulting in Treg differentiation via PGE2-EP2 signaling [17]
These protective effects were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 treatment is an important regulator of Treg-dependent maintenance of pregnancy
Summary
Pregnancy has been considered a state of maternal immunological tolerance because the maternal immune system protects the semi-allogenic fetus during the implantation period. In vivo prevention of the fetal resorption of abortion-prone mice was achieved after adoptive transfer of Treg cells from the spleens of normal pregnant mice at mid-pregnancy [13]. BvPLA2 pretreatment prevented fetal loss accompanied by growth restriction by inducing Treg cells. We determined the effects of Treg depletion following bvPLA2 treatment in LPS-induced abortion. Treatment of LPS-induced abortion mice with bvPLA2 diminished the risk of fetal death. These protective effects were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 treatment is an important regulator of Treg-dependent maintenance of pregnancy
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