Paternal exposure to microcystin-LR induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in placental labyrinth

Gao, Lan; Cui, An-Qi; Wang, Jing; Chen, Jing; Zhang, Xiao-Yi; Lin, Zhi-Jing; Chen, Yuan-Hua; Zhang, Cheng; Wang, Hua; Xu, De-Xiang

Paternal exposure to microcystin-LR induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in placental labyrinth

2021

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. Male mice were intraperitoneally injected with either normal saline or MC-LR (10 μg/kg) daily for 35 days. Male mouse was then mated with female mice with 1:1 ratio. 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. 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.

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