Mechanism of vulnerability formation by nutritional environment change at developmental stage.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Showa University
• Principal Investigator: Kuwagata Makiko 昭和大学, 医学部, 客員教授 (70398684)
• Research Collaborator: Shibatoh Junko ; Ogawa tetsuo ; Rakwal Randeep
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: DoHaD / 遺伝子解析 / 新生児期栄養環境 / マウス / LPS

Outline of Final Research Achievements

We have investigated candidate genes which are associated with increased risk of adult diseases by analyzing developing tissues from the C57BL/6J mouse model of developmental origins of health and disease (DOHaD). We focused on experimental evidence that the effect of undernutrition on adult offspring is opposite between the fetal and neonatal periods. We selected 21 candidate genes which were expressed opposite between prenatal and neonatal undernutrition. After 7-days neonatal 50% food restriction in dam, offspring kept until 11-weeks of age. At 11-weeks of age, LPS (TLR4 inducer) was administered to offspring and expression of 21 candidate genes were examined. One of 21 genes such as OATP family transporter (Slco2b1) were affected, and development of spleen and thymus altered after neonatal undernutrition. Adult LPS treatment changed 4 genes such as Lrtm1, Mrap, Il1b, and Slco2b1 between neonatal FR offspring and control offspring. These four genes may be candidate genes for DOHaD.

Free Research Field

生殖発生毒性

Academic Significance and Societal Importance of the Research Achievements

マウス新生児期の低栄養曝露により、成熟期においても影響が継続していた遺伝子( Slco2b1)が選抜された。また、成熟期のLPS投与に対する反応が、新生児期の低栄養曝露により影響を受けていた。本課題で得られた結果は、これまで注目されてきた胎生期の栄養環境のみではなく、新生児期の栄養環境の変化も、個体の脆弱性に影響を及ぼすことを明らかにした。