Absence of maternal-derived gal-3 drives unusual placentation increasing the risk of FGR.

XIE Y; VERKAIK-SCHAKEL RN ; ZHAO F; GARCIA MG; PLÖSCH T; BLOIS SM

Congreso; 16th Annual Meeting of the European Society for Reproductive Immunology (ESRI); 2022

Problem: Fetal growth restriction (FGR) is a pathological condition that poses life-long impacts. To date, the mechanism of FGR is not fully understood. We recently showed that deficiency of galectin-3 (gal-3), a β-galactoside binding protein, leads to placental dysfunction and drives FGR. This study investigated the contribution of maternal- and paternal-derived gal-3 to placental function and fetal growth. Method of study: Reciprocal matings were used to achieve the lack of maternal (mating of gal-3+/+ (WT) male with gal-3−/− (KO) female, mKO) and paternal (mating of gal-3−/− (KO) male with gal-3+/+ (WT) female, pKO) gal-3. Placenta structure and function along with fetal growth was evaluated embryonic day (E) 13. Results: The absence of maternal gal-3 increased fetal demise. In addition, the body weight of gal-3+/− fetuses derived from gal-3−/− dams (mKO) was significantly reduced compared to gal-3+/− fetuses carried by gal-3+/+ dams (pKO). Fetuses derived from mKO dams showed also a delayed fetal development compared to fetuses carried by pKO on E13. Moreover, mKO implantations displayed a decreased fetal/placental weight ratio, indicative of placental insufficiency, along with a reduced thickness of the junctional zone layer with fewer glycogen cells. Maternal gal-3 deficiency induced an inflammatory phenotype of uterine NK cells and imbalance on the placenta oxidative stress response. Furthermore, mKO placentas showed an unusual glycophenotype and impaired expression of genes involved in trophoblast differentiation. Conclusion: Our data highlight the importance of maternal gal-3 on proper placental development, with ramifications for fetal growth.