A clinical and experimental study on the pathophysiology of pregnancy by comprehensive gene analysis in peripheral blood NK cells from prepregnancy to 1st-trimester

Research Project

Project/Area Number	16K20203
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Obstetrics and gynecology
Research Institution	Jichi Medical University
Principal Investigator	Ishida Yoichi 自治医科大学, 医学部, 助教 (70772143)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000) Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	末梢血NK細胞 / 妊娠 / 網羅的遺伝子発現解析 / microRNA / 妊娠維持機構 / 網羅的解析 / 遺伝子発現 / マイクロRNA / 生殖医学 / 母児免疫 / NK細胞 / マイクロアレイ
Outline of Final Research Achievements	To elucidate whether peripheral natural killer cells (pNKs) were associated with the pathophysiology of feto-maternal tolerance, we obtained peripheral bloods for prepregnancy (follicular phase and luteal phase) and during pregnancy (1st, 2nd, 3rd-trimester), and then separated pNKs, subsequently extracted RNA. The number of pNKs increased significantly from follicular phase to luteal phase, while the number decreased significantly from luteal phase to 1st-trimester, and decreased even further from 1st-trimester to 3rd-trimester. Moreover, they decreased during pregnancy compared to pre-pregnancy. We hypothesized that gene expressions of pNKs may be changed from follicular phase to luteal phase, and from luteal phase to 1st-trimester. We plan to perform comprehensive gene analysis of pNKs using the extracted RNA from pNKs.
Academic Significance and Societal Importance of the Research Achievements	今回の検討で、母体末梢血NK細胞数(pNK)が妊娠前から妊娠中にかけて有意に変動していた。この結果から、pNKが妊娠維持機構に関与している可能性が示唆された。このことは、いまだ病態が解明されていない不育症や早産、また妊娠高血圧症候群、常位胎盤早期剥離など、妊娠期に発症する疾患の原因解明や治療の向上につながる可能性がある。今後、妊娠前の卵胞期・黄体期と妊娠初期の母体末梢血NK細胞の網羅的遺伝子発現解析を施行して、まだ未解明な部分の妊娠維持機構を明らかにする予定である。