Progesterone fluctuated signals in females induced by reproductive aging

2022 Fiscal Year Research-status Report

• Project/Area Number: 21K15010
• Research Institution: Nagoya City University
• Principal Investigator: シャウキ ホッサム 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70829738)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: reproductive aging / progesterone

Outline of Annual Research Achievements

In 2022, we cleared reproductive phenotypes of Tcf23 knockout (KO) mice. The female KO mice showed no defects of decidualization of endometrium and the maintenance of pregnancy; however the myometrium of aged KO mice poorly responded to the oxytocin and other contraction stimuli. To understand the mechanism more deeply, RNA-seq analysis of KO myometrium was performed, and the results showed several contraction-related genes were downregulated in KO mice. In addition, based on the previous publication, there was an new possible protein to directly bind to Tcf23 and control the myometrium function. Tcf23 might negatively regulate the myometrium contraction by foming the heterodimer with the unkonwn protein and block it's function.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Two thirds of the project has been completed.

Strategy for Future Research Activity

I am planing to find molecules to bind Tcf23 and control the myometrium function as well as the downstream targets of Tcf23, which causes the abnormal status during pregnancy. In 2023, the roles of Tcf23 and related signal transduction will be examined as a negative regulator of progesterone. The output of the current project will support maintaining suitable strategies of caring an aged woman during pregnancy, which is a burgeoning clinical problem.

Causes of Carryover

Some of the experiments planned in 2022 has been shifted to 2023.