Elucidating the effects of advanced maternal age on placenta with trophoblast organoids

• Applicant: Dr. Violeta Stojanovska
• Subject Area: Reproductive Medicine, Urology ; Gynaecology and Obstetrics
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545849649

The average age of women giving birth in the past couple of decades has steadily increased worldwide. Giving birth after the age of 35 is categorized as advanced maternal age (AMA), deemed “high-risk” for developing pregnancy-associated disorders and fetal abnormalities. However, to date, it is still not clear how exactly AMA affects early placental development. With this project we aim to understand the placental fitness of AMA pregnancies by utilization of placenta organoids. Obtained from elective terminations of pregnancies, these organoids serve as a proxy for human placental development and overcome species-specific differences, in contrast to the utilization of animal models. The placenta organoids will be derived from optimal (18-30 years old) and advanced maternal age (>=35 years old) pregnancies to address two main objectives. Primarily, we will identify the effects of AMA on trophoblast functionality by assessing the organoid´s proliferation rate, differentiation, and invasive capabilities. Secondly, we will establish single-cell transcriptomics, proteomics and imaging data on “optimal” and “AMA”-derived organoids. Ultimately, this will enable morphological and functional characterization of trophoblast population variations per age and provide a baseline for future pregnancy-associated disease studies.

• DFG Programme: Research Grants