The Triangle of Pregnancy Success – Decoding the Network between Regulatory T Cells, Dendritic Cells and Human Chorionic Gonadotropin in Embryo Implantation

• Applicant: Privatdozentin Dr. Anne Schumacher
• Subject Area: Reproductive Medicine, Urology ; Gynaecology and Obstetrics
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422013072

Infertility, particularly in industrialized countries, cannot longer be considered a personal problem but represents rather a public health issue whose significance arises rapidly. The inability to conceive a child does not only result in personal conflicts but has also been associated with psychological and even psychiatric disorders. Beside intensive costs for infertility treatments there are further costs involved managing mental health complications. For this reason, a detailed understanding of mechanisms underlying each step of a successful pregnancy is essential. Ultimately, this will contribute to therapeutic interventions for couples suffering from undesired childlessness and reduce the number of patients developing mental disorders due to reproductive failure. One milestone of pregnancy is represented by the adequate implantation of the embryo into the maternal endometrium. Proper embryo implantation is a prerequisite for successful pregnancy progression without placenta-associated complications. However, despite intensive research activity, the mechanisms underlying embryo implantation are far from being understood. Several own and other studies indicate a critical involvement of various hormones and immune cell populations in the implantation process and suggest endocrine-immune interdependencies. The proposed research project primarily focuses on the participation of regulatory T cells (Treg) and dendritic cells (DCs) in embryo implantation. Secondary, it will be clarified whether the pregnancy hormone human chorionic gonadotropin (hCG) influences both immune cell types in their functionality. To achieve this, the following scientific questions will be addressed: (1) Do Treg and DCs affect fundamental steps during embryo implantation such as trophoblast adhesion and invasion into the maternal endometrium? (2) Which implantation-related factors are influenced by Treg and DCs? and (3) Does hCG support Treg and DCs in fostering embryo implantation? In vitro analyses using human and murine implantation models as well as in vivo analyses in transgenic mouse strains will be applied.Our results will advance the state-of-the-art in the reproductive immunology field by gaining more knowledge about the relevance of the maternal immune systems for a proper embryo implantation process. Based on this knowledge, we hope that our research will build bridges between basic research and clinical application resulting in novel and advanced therapeutic interventions for infertile patients.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Ana Claudia Zenclussen