Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction

Abstract

The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt to damage or changes in the environment. By using stereology and expression of cell cycle markers, we found that the placenta grows under normal conditions not just by hyperplasia of trophoblast cells but also through extensive polyploidy and cell hypertrophy. In response to feeding a low protein diet to mothers prior to and during pregnancy, to mimic chronic malnutrition, we found that this normal program was altered and that it was influenced by the sex of the conceptus. Male fetuses showed intrauterine growth restriction (IUGR) by embryonic day (E) 18.5, just before term, whereas female fetuses showed IUGR as early as E16.5. This difference was correlated with differences in the size of the labyrinth layer of the placenta, the site of nutrient and gas exchange. Functional changes were implied based on up-regulation of nutrient transporter genes. The junctional zone was also affected, with a reduction in both glycogen trophoblast and spongiotrophoblast cells. These changes were associated with increased expression of Phlda2 and reduced expression of Egfr. Polyploidy, which results from endoreduplication, is a normal feature of trophoblast giant cells (TGC) but also spongiotrophoblast cells. Ploidy was increased in sinusoidal-TGCs and spongiotrophoblast cells, but not parietal-TGCs, in low protein placentas. These results indicate that the placenta undergoes a range of changes in development and function in response to poor maternal diet, many of which we interpret are aimed at mitigating the impacts on fetal and maternal health.

An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD

“…Our work also reveals that the capacity for placental adaptation to support fetal growth is sex-dependent. This phenomenon is not limited to maternal alcohol intake or protein insufficiency but is commonly reported in studies investigating other prenatal stressors including maternal dietary restriction, maternal asthma, preeclampsia, and gestational diabetes [52][53][54][55][56][57]. Although well-documented, the underlying basis for these sexdependent placental responses remains unclear.…”

Single nuclei RNA-seq of mouse placental labyrinth development

“…One (clusters 6, 10, and 24) expressed markers of pericytes (e.g. Acta2 ) and several growth factors including Wnt5b and Pdgfrb that are critical for development and maintenance of vascular populations ( Eaton et al, 2020 ). The other (clusters 15 and 19) expressed Gata4 , Kit, and Pdpn.…”

Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

“…The mouse placenta is comprised of three distinct zones; the maternally derived decidua, and the conceptus-derived junctional and labyrinth zones. The labyrinth zone consist of two layers of multinucleated syncytiotrophoblast (SynT) cells resulting in a large surface area for nutrient and gas exchange between mother and fetus [ 27 ]. Blinded histological analysis of placental sections showed that the area of labyrinth zone was significantly reduced in mRUPP compared to Sham ( Fig.…”