Embryo-maternal communication in early pregnancy revisited: understanding the role of PPARa and PPARg in the hidden impact of an advanced maternal age and metabolic stress (ComPPARage)

• Applicant: Dr. Maria Schindler
• Subject Area: Reproductive Medicine, Urology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545844002

A woman's late decision to have children often leads to involuntary childlessness in couples. In women over the age of 35, even assisted reproduction (ART) cannot compensate for an age related decline in female fertility. In addition to physiologically reduced ovarian function, metabolic changes in reproductive tract organs are considered the main reason for this. During the preimplantation phase, the intrauterine environment is regulated by the woman's metabolism and endocrine system and thus sets the course for the optimal care of the embryo. Using the rabbit as a model for early embryo developmental in mammals, we were able to show that ageing and metabolic stress of the mother have a detrimental effect on pre-implantation development. In reproductively old rabbits, the expression of the peroxisome proliferator-activated receptors (PPAR) a and g, two central transcription factors of uterine and embryonic signaling was altered in both maternal and embryonic tissues. The aim of the proposed 1-year project is to elucidate the mechanism of impaired PPAR signaling and the consequences for the implantation phase. To this purpose, the metabolic changes and molecular adaptation reactions in the endometrium and embryo will be analyzed using metabolomics and proteomics, and specific expression analyses in the rabbit development model in vivo and by primary endometrial cell culture in vitro. The pilot project will clarify which maternal factors regulate PPAR signaling during the implantation phase. The results will then be used to derive how PPAR regulation can be controlled in vivo (women’s health) and in vitro (ART) in order to compensate for the age-related disadvantages in the preimplantation phase and to prevent potentially negative effects on embryo development.

• DFG Programme: Research Grants