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

不孕症，特别是在工业化国家，不再被视为个人问题，而是一个重要性迅速显现的公共健康问题。不能怀孕不仅会导致个人冲突，还会导致心理甚至精神疾病。除了不孕不育治疗的高额费用外，还有管理精神健康并发症的费用。因此，详细了解成功怀孕的每个步骤背后的机制是必不可少的。最终，这将有助于对遭受非意愿生育的夫妇进行治疗干预，并减少因生殖失败而发展为精神障碍的患者人数。怀孕的一个里程碑是胚胎充分植入母体子宫内膜。适当的胚胎植入是妊娠顺利进展而无胎盘相关并发症的先决条件。然而，尽管有大量的研究活动，胚胎着床的机制还远未被理解。一些自己和其他研究表明，各种激素和免疫细胞群在植入过程中起着关键作用，并表明内分泌-免疫相互依赖。拟建的研究项目主要关注调节性T细胞（Treg）和树突状细胞（DCs）在胚胎着床中的参与。其次，将澄清妊娠激素人绒毛膜促性腺激素（hCG）是否影响两种免疫细胞类型的功能。为了实现这一目标，将解决以下科学问题：(1)Treg和dc是否影响胚胎着床过程中的基本步骤，如滋养细胞粘附和侵入母体子宫内膜？(2) Treg和DCs对哪些植入相关因素有影响？(3) hCG是否支持Treg和dc促进胚胎着床？在体外分析使用人类和小鼠植入模型以及在体内分析转基因小鼠株将被应用。我们的结果将通过获得更多关于母体免疫系统与适当胚胎植入过程的相关性的知识，推进生殖免疫学领域的最新技术。基于这些知识，我们希望我们的研究将在基础研究和临床应用之间建立桥梁，从而为不孕症患者提供新颖和先进的治疗干预措施。

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.