Maternal derived-galectin-3 impacts on placental-fetal development leading to FGR

Fetal growth restriction (FGR), a serious pregnancy complication, is commonly associated with perinatal morbidity and mortality. To date, the underlying mechanism of FGR remains unknown. Our previous work showed that deficiency of galectin-3 (gal-3), a β-galactoside binding protein, results in placental dysfunction and subsequent FGR. Since gal-3 is expressed at both sides of the maternal-fetal interface, we investigated the contribution of maternal- and paternal-derived gal-3 on fetal development in the prenatal and post-natal periods. Reciprocal matings were used to achieve the lack of maternal (mating of Lgals3+/+ (WT) male with Lgals3−/− (KO) female, mKO) and paternal (mating of Lgals3−/− (KO) male with Lgals3+/+ (WT) female, pKO) gal-3. Deficiency of maternal gal-3 contributes to the development of asymmetric FGR increasing the fetal demise with an impact on female offspring growth in the post-natal period. During the prenatal window, placental insufficiency manifested by retarded trophoblast differentiation and impaired vascularization in the labyrinth layer was observed in the absence of maternal-derived gal-3. In addition, pro-inflammatory milieu and epigenetic dysregulation were associated with maternal gal-3 deficiency. Taken together, our findings highlight the importance of maternal gal-3 on proper placental function, and its implications on fetal development, suggesting a protective role of gal-3 in maternal adaptations to pregnancy.