Progesterone fluctuated signals in females induced by reproductive aging

2021 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 – 2023-03-31
• Keywords: reproductive aging / progesterone

Outline of Annual Research Achievements

Reproductive aging implies a sharp decline in female fertility and an increase in pregnancy complications with maternal age. The major characteristics of reproductive aging are low birth rate/embryonic malformation caused by defective decidualization at early pregnancy, and prolong gestational period at late pregnancy. At early pregnancy, progesterone at a specific level is required to induce successful endometrial decidualization, while in late pregnancy progesterone withdrawal from myometrium is mandatory for starting myometrial contraction and on-time delivery. A higher level of progesterone than optimal during early or late pregnancy reported to cause defective decidualization as well as delayed delivery, respectively. In aged female mice, we observed a minor change in Estrogen but higher progesterone levels than young mice in early pregnancy with no progesterone withdrawal at late pregnancy, which can be the cause of the defective decidualization and the long gestation. The defective homeostasis of progesterone levels in aged females has not been characterized yet. This year, I cleared the molecular mechanisms controlling normal progesterone levels during early and late stages of pregnancy.

Current Status of Research Progress

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

Reason

Half of the project has been completed.

Strategy for Future Research Activity

I am planing to The downstream targets of progesterone causing the abnormal physiological status during pregnancy. As a preliminary result, we found a Class II Basic Helix-Loop-Helix protein (TCF23) deletion in 6M old mice showed an abnormal/inflamed uterine decidua and obstructed labor, which might indicate its role as 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 experiment planned in 2021 has been shifted to 2022.