Transcriptional profiling of healthy versus cystic fibrosis human endometrial organoids upon hormonal exposure

Female cystic fibrosis (CF) patients are confronted with fertility deficiency, experiencing difficulties in getting pregnant. Underlying reasons remain elusive. 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. One main reason is the lack of reliable and tractable study models given the major technical and ethical hurdles to study events that occur hidden in the womb.To overcome this, we established an endometrium CF organoid model. We applied bulk RNA sequencing on these organoids derived form endometrium of women affected by CF and of healthy women. These endometrial organoids (EO) were exposed to hormones to mimic different phases of the menstrual cycle. The proliferative phase was mimicked by exposing the EO to estradiol (+E2), while the (mid-)secretory phase was mimicked by estradiol, progesterone, cyclic AMP and XAV-939 (Wnt inhibitor) (EPCX) exposure of EO. As a control, we sequenced healthy and CF EO not exposed to hormones (EOM).