The endometrium, the lining of the uterus, regenerates every month, but how this happens is poorly understood. Now, researchers in the group of Margherita Turco have recreated the menstrual cycle in the lab using tiny 3D structures called endometrial organoids, which mimic the natural breakdown and regrowth of the uterine lining in response to hormones. Their system allows scientists to follow how different cell types interact and regenerate tissue over time.

A key discovery was the role of WNT7A, a gene active in cells on the surface of the uterine lining. WNT7A’s expression spikes soon after tissue breakdown and helps guide cells through the repair process, supporting their survival and regrowth. The researchers also found that these regenerating cells send signals to other cell types, such as immune cells and blood vessel cells, releasing molecules that promote wound healing and new blood vessel formation.

The surface layer of the endometrium, called the luminal epithelium, has an underappreciated role in uterine regeneration, with the most prevalent theory being that regeneration starts from cells located deeper in the tissue, says study lead author Konstantina Nikolakopoulou. “Our findings show that the luminal epithelium adopts a wound-healing identity during menstruation and functions as a signalling hub,” she says.

The lab-grown endometrial organoids closely mirror what happens in the human uterus, allowing the tracking of cell behavior that isn’t possible in people. “Despite affecting hundreds of millions of women every day, menstruation has historically received little scientific attention, and we wanted to create a model that could finally open this ‘black box’,” Turco says.

While the current model focuses on the endometrium’s epithelial cells, it opens the door for more complex studies that include other cell types, helping researchers understand conditions such as endometriosis and heavy menstrual bleeding.

Beyond women’s reproductive health, the findings also shed light on fundamental principles of tissue repair. By uncovering the role of WNT7A and the signals that coordinate regeneration, the study offers new insight into how healing occurs and may inform future therapies to improve tissue repair in other organs.

Learn more about this work by watching this video.