title: Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition.
abstract: Mammalian extra-embryonic lineages perform the crucial role of nutrient provision during gestation to support embryonic and fetal growth. These lineages derive from outer trophectoderm (TE) and internal primitive endoderm (PE) in the blastocyst and subsequently give rise to chorio-allantoic and visceral yolk sac placentae, respectively. We have shown maternal low protein diet exclusively during mouse preimplantation development (Emb-LPD) is sufficient to cause a compensatory increase in fetal and perinatal growth that correlates positively with increased adult-onset cardiovascular, metabolic and behavioural disease. Here, to investigate early mechanisms of compensatory nutrient provision, we assessed the influence of maternal Emb-LPD on endocytosis within extra-embryonic lineages using quantitative imaging and expression of markers and proteins involved. Blastocysts collected from Emb-LPD mothers within standard culture medium displayed enhanced TE endocytosis compared with embryos from control mothers with respect to the number and collective volume per cell of vesicles with endocytosed ligand and fluid and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor. Endocytosis was also stimulated using similar criteria in the outer PE-like lineage of embryoid bodies formed from embryonic stem cell lines generated from Emb-LPD blastocysts. Using an in vitro model replicating the depleted amino acid (AA) composition found within the Emb-LPD uterine luminal fluid, we show TE endocytosis response is activated through reduced branched-chain AAs (leucine, isoleucine, valine). Moreover, activation appears mediated through RhoA GTPase signalling. Our data indicate early embryos regulate and stabilise endocytosis as a mechanism to compensate for poor maternal nutrient provision.
authors: Centre for Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Congshan
authors: C
authors: Sun
authors: Miguel A
authors: MA
authors: Velazquez
authors: Stephanie
authors: S
authors: Marfy-Smith
authors: Bhavwanti
authors: B
authors: Sheth
authors: Andy
authors: A
authors: Cox
authors: David A
authors: DA
authors: Johnston
authors: Neil
authors: N
authors: Smyth
authors: Tom P
authors: TP
authors: Fleming
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002478:Cells, Cultured; D018753:Diet, Protein-Restricted; D004705:Endocytosis / Q000502:physiology*; D004707:Endoderm / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D051379:Mice; D011247:Pregnancy; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020742:rhoA GTP-Binding Protein
keywords: Embryoid body; Endocytosis; Maternal diet; Mouse embryo; Primitive endoderm; RhoA; Trophectoderm