Paternal Exposure To Microcystin-LR Induces Fetal Growth Restriction Partially Through Inhibiting Cell Proliferation And Vascular Development In Placental Labyrinth

Objectives Microcystin-leucine arginine(MC-LR)has reproductive and developmental toxicities.Previous studies indicated that gestational exposure to MC-LR induced fetal growth restriction in mice.The aim of this study was to further evaluate the effect of paternal MC-LR exposure before mating on fetal development.Methods Male mice were intraperitoneally injected with either normal saline or MC-LR(10 μg/kg)daily for 35 d.Male mouse was then mated with female mouse with 1:1ratio.Results There was no significant difference on the rates of mating and pregnancy between MC-LR-exposed male mice and controls.Body weight and crown-rump length were reduced in fetuses whose fathers were exposed to MC-LR.Despite no difference on relative thickness of labyrinthine layer,cell proliferation,as measured by Ki67 immunostaining,was reduced in labyrinth layer of MC-LR-exposed mice.Moreover,blood sinusoid area in labyrinth layer was decreased in the fetus whose father was exposed to MC-LR before mating.Correspondingly,cross-sectional area of CD34-positive blood vessel in labyrinth layer was lower in fetuses whose fathers were exposed to MC-LR than in controls.Conclusions These results provide evidence that paternal MC-LR exposure before mating induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in labyrinth layer.