Marilen Benner

CHAPTER 6 140 INTRODUCTION Maternal microbial colonization contributes to development of the unborn child by micronutrient provision, xenobiotic metabolism and enhancing maternal energy conversion (1). Currently, the concept of the “sterile womb”, the paradigm that the fetus grows up in a sterile environment, is highly debated (2). If bacteria (or their compounds) were naturally present in the uterus, their role even before pregnancy, in maintenance of the uterus deserves attention. Various recent reviews focused on correlations between commensal uterine colonization, fertility problems and pregnancy complications (3-6). Bacteria are known to affect immunity (7, 8). If they already impact the immune environment of the uterus before pregnancy, this would greatly impact the receptive potential of the endometrium, as well as the ability to correctly initialize placenta formation. Successful embryo implantation requires both a synchronous development and an intricate interplay between the hatched blastocyst and endometrium. This depends on a receptive state of the endometrium. In the first week after fertilization, the blastocyst makes initial contact with the highly specialized endometrium. During the female cycle, if the endometrium fails to undergo the proper adaptations to acquire this receptive state, infertility and impaired placentation may be the consequence. Since bacteria can play a role in morphological changes of, for example, mucosal cells, implications of microbiota in decidualization can be envisioned. At the same time, commensal microbiota may convey protection towards pathogenic species contributing to uterine health. Studies evaluating the endometrial microbiome and its role in fertility are limited and therefore we depend on extrapolating knowledge from other colonized body sites. A vast number of studies focusing on the gut microbiota have pointed out the contribution of microbes to immunity and development, and the necessity of commensal colonization to achieve a basal, healthy immune state (7, 9, 10). We hypothesize that, if indeed present, the endometrial microbiome or its compounds can have implications for (pre-) decidualization, and therefore fertility. The objective of this review is to outline the available evidence regarding uterine microbiota, focusing on recent findings based on 16S rRNA, and to depict the possible importance of uterine colonization for a receptive endometrium. We aim to highlight a possible role of uterine microbiota in host immunity and tissue adaptation, as well as conferring protection against pathogens.