Decreased fertility in female cystic fibrosis patients: deciphering the role of the endometrium using state-of-the-art organoid models

Cystic fibrosis (CF) remains a burdening genetic disease. Female CF patients are confronted with decreased fertility, experiencing difficulties in getting pregnant. Underlying reasons remain largely unclear. In particular, it has only poorly been studied whether the endometrium, the inner lining of the womb and crucial tissue for embryo implantation, plays a role. This gap is mainly due to lack of appropriate study models. Recently, we developed state-of-the-art organoids from mouse and human endometrium that faithfully recapitulate endometrium physiology, climaxing in the competence to imitate the menstrual cycle in the lab. Furthermore, we established organoids from endometrial diseases, thereby showing the compelling capacity to model diseased endometrium using organoids. Here, we will develop organoids from endometrium of genetic CF mice and human CF patients. The organoids will in detail be compared with healthy endometrium-derived organoids to identify key differences. Moreover, we will investigate endometrium fitness of CF patients using a co-culture system combining synthetic embryos with organoid-based endometrium replica. Our study is expected to provide insights into the role of the endometrium in CF-associated sub-/infertility, and has the potential to reveal new ideas toward therapy restoring reproductive fitness, which can be tested using organoids. In the end, we aim at providing knowledge to help CF couples to have children, which remains difficult now.