Studies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110α in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110α resulted in viable fetuses, abnormal placental development and a failure of the placenta to transport sufficient nutrients to match fetal demands for growth. Using RNA-seq we identified genes downstream of p110α in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110α differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110α in the different compartments of the conceptus, which control fetal resource acquisition and growth.

ObjectiveThis systematic review examines the qualitative literature on women’s experiences of self-managing chronic conditions in pregnancy.DesignSystematic review of qualitative literature. Searches were performed in PubMed and CINAHL from inception to February 2021. Critical interpretive synthesis informed the coding framework and the analysis of the data. The Burden of Treatment theory emerged during the initial analysis as having the most synergy with the included literature, themes were refined to consider key concepts from this theory.ParticipantsPregnant women who are self-managing a chronic condition.ResultsA total of 2695 articles were screened and 25 were reviewed in detail. All 16 included studies concerned diabetes self-management in pregnancy. Common themes coalesced around motivations for, and barriers to, self-management. Women self-managed primarily for the health of their baby. Barriers identified were anxiety, lack of understanding and a lack of support from families and healthcare professionals.ConclusionsPregnant women have different motivating factors for self-management than the general population and further research on a range of self-management of chronic conditions in pregnancy is needed.PROSPERO registration numberCRD42019136681.

32Previous studies suggest that the placental supply of nutrients to the fetus adapts according to fetal 33 demand. However, the signaling events underlying placental adaptations remain largely unknown. Earlier 34 work in mice has revealed that loss of the phosphoinositide 3-kinase p110α impairs feto-placental growth 35 but placental nutrient supply is adaptively increased. Here we explore the role of p110α in the epiblast-36 derived (fetal) and trophoblast lineages of the conceptus in relation to feto-placental growth and placental 37 development and transfer function. Using conditional gene manipulations to knock-down p110α either by 38 ~50% or ~100% in the fetal lineages and/or trophoblast, this study shows that p110α in the fetus is 39 essential for prenatal development and a major regulator of placental phenotype in mice. Complete loss of 40 fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and 41 impaired placental formation and nutrient transport. Loss of trophoblast p110α also resulted in abnormal 42 placental development, although fetuses were viable. However, in response to complete loss of 43 trophoblast p110α, the placenta failed to transport sufficient amino acid to match fetal demands for 44 growth. Using RNA-seq, we identified several genes downstream of p110α in the trophoblast that are 45 important in adapting placental phenotype to support fetal growth. Further work using CRISPR/Cas9 46 genome targeting showed that loss of p110α differentially affects the expression of genes in trophoblast 47 and embryonic stem cells. Our findings thus reveal important, but distinct roles for p110α signaling in the 48 2 different compartments of the conceptus, which control fetal resource acquisition and ultimately affect 49 healthy growth. 50 51

No abstract