期刊
BIOLOGY OF REPRODUCTION
卷 78, 期 2, 页码 299-306出版社
OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod.107.064220
关键词
behavior; blastocyst; blood pressure; conceptus; developmental biology; embryo; environment; growth; low protein diet; megalin; preimplantation embryo; yolk sac
资金
- Biotechnology and Biological Sciences Research Council [G18784, BB/F007450/1] Funding Source: Medline
- Medical Research Council [G0100558] Funding Source: Medline
- NICHD NIH HHS [U01 HD044635] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/F007450/1, G18784] Funding Source: researchfish
- Medical Research Council [G0100558] Funding Source: researchfish
- BBSRC [BB/F007450/1] Funding Source: UKRI
- MRC [G0100558] Funding Source: UKRI
Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase susceptibility to adult cardiovascular and metabolic diseases. However, underlying mechanisms are largely unknown. Here, we show that maternal low protein diet (LPD), fed exclusively during mouse preimplantation development, leads to offspring with increased weight from birth, sustained hypertension, and abnormal anxiety-related behavior, especially in females. These adverse outcomes were interrelated with increased perinatal weight being predictive of later adult overweight and hypertension. Embryo transfer experiments revealed that the increase in perinatal weight was induced within blastocysts responding to preimplantation LPD, independent of subsequent maternal environment during later pregnancy. We further identified the embryo-derived visceral yolk sac endoderm (VYSE) as one mediator of this response. VYSE contributes to fetal growth through endocytosis of maternal proteins, mainly via the multiligand megalin (LRP2) receptor and supply of liberated amino acids. Thus, LPD maintained throughout gestation stimulated VYSE nutrient transport capacity and megalin expression in late pregnancy, with enhanced megalin expression evident even when LPD was limited to the preimplantation period. Our results demonstrate that in a nutrient-restricted environment, the preimplantation embryo activates physiological mechanisms of developmental plasticity to stablize conceptus growth and enhance postnatal fitness. However, activation of such responses may also lead to adult excess growth and cardiovascular and behavioral diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据