Marilen Benner

MICROBIOTA AND ENDOMETRIAL HEALTH 153 6 to the results from endometrial material, we should consider a physiological importance of local microbiota. ENDOMETRIUM – STARTING POINT FOR DECIDUALIZATION, IMPLANTATION AND PLACENTATION To understand how microbiota could play a role in the uterine interplay of cells involved in the per-implantation period, we first need to understand how the endometrium forms the basis for successful implantation and placentation. Despite the growing interest from both clinicians and scientists in the process of implantation, the mechanisms underlying human implantation remain poorly understood. Each month, before the presence of a developing embryo, the stage for formation of the placenta is set. During the mid-to-late luteal phase spontaneous decidualization occurs; i.e. the transformation of the endometrium into a receptive state, independent of the presence or absence of a conceptus. Six to 10 days after ovulation (during day 19-24 of the menstrual cycle) the receptive stateof theendometrium is shaped. This is referred toas ‘thewindow of implantation’ (WOI), lasting for 2-4 days (70, 71). The substantial physiological adaptations needed for correct cyclical changes of the endometrium are orchestrated by fluctuations of progesterone and oestrogen (72, 73), as well as by immune cells and their products (74, 75). Endometrial stromal fibroblasts differentiate to become larger, rounded fibroblast-like stromal cells. To achieve this, the cytoskeleton and plasma membrane undergo modifications (76-78). The luminal epithelium must be able to interact with the blastocyst. Interactions also involve adhesion molecules, such as integrins, L-selectin ligands (e.g. L-selectin ligands expressed by the luminal epithelium and L-selectin receptors of the blastocyst), and oligosaccharides (79-82). We summarized key endometrial adaptations in the peri-implantation period (Figure 1) to show the importance of enabling the correct interaction of endometrium and blastocyst. Already at this stage, irreversible shortcomings in placental vascularization pose an origin for diseases such as pre-eclampsia or intra-uterine growth restriction (83). On the maternal side, the underlying mechanisms regulating correct migration of the trophoblast and vascular remodeling may be rooted in the endometrium. Due to its importance for correct placentation, the endometrium is crucial for developing a healthy placenta, and therefore a healthy pregnancy (84). If microbial compounds constitute another physiologic player in the complex uterine environment, its natural impact will likely also contribute to implantation and placentation.