Interaction between sex hormones and WNT/β-catenin signal transduction in endometrial physiology and disease

► During early development, Wnt signalling is essential for Müllerian duct development. ► In physiology, Wnt signalling regulated by sexhormones maintains monthly homeostasis. ► During pregnancy Wnt signalling is essential for proper implantation and placentation. ► Enhanced myometrial Wnt/β-catenin signalling may induce adenomyosis. ► Continuous endometrial Wnt signalling induces hyperplasia and may lead to cancer. Wnt/β-catenin signalling plays a rate-limiting role in early development of many different organs in a broad spectrum of organisms. In the developing Müllerian duct, Wnt/β-catenin signalling is important for initiation, outgrowth, patterning and differentiation into vagina, cervix, uterus and oviducts. In adult life, sex hormones modulate Wnt/β-catenin signalling in the endometrium to maintain the monthly balance between estrogen-induced proliferation and progesterone-induced differentiation, and enhanced Wnt/β-catenin signalling seems to be involved in endometrial carcinogenesis. However, early in pregnancy enhanced Wnt/β-catenin signalling is prerequisite for proper implantation and invasion of trophoblast cells into endometrium and myometrium thus helping to form a placenta. Overall, it seems that tight control of Wnt/β-catenin signalling in time and space is important for initiation, development and normal function of the female reproductive tract. However, if Wnt/β-catenin signalling is not kept in check, it easily seems to initiate or contribute to development of a number of uterine disorders.