In human pregnancy normal implantation and development of the feto-placental unit is dependent on transformation of the uterine lining from endometrium to decidua. The formation of decidua is essential for normal pregnancy. In a non-pregnant cycle the endometrium breaks down at menstruation and a similar process occurs in a failing pregnancy at miscarriage. The cellular and molecular processes responsible for formation of decidua or endometrial breakdown are largely unknown. The hypothesis underlying this proposal is that the unusual population of uterine mucosal leucocytes, uterine Natural Killer (N K) cells, play a pivotal role in the critical decision that the secretory endometrium must make either to decidualise or undergo menstruation. The functions of uterine NK cells are unknown, but they are most abundant in species which undergo mucosal decidualisation and they are an integral part of decidua. In non-pregnant cycles they undergo apoptosis 2-3 days preceding menstrual breakdown before there are no other morphological features of menstruation. The specific questions are: 1) Are the NK cells in the uterine mucosa recruited from the blood? 2) What factors in the uterine microenvironment are responsible for triggering NK cell apoptosis or maintaining NK cell survival? 3) Can uterine NK cells influence the process of decidualisation? This work will increase understanding of two crucial processes in human reproductive physiology - decidualisation and menstruation. Therefore this work will have a major impact on women's health. It could lead to novel therapeutic approaches in a wide range of disorders including infertility, miscarriage, disorders due to defective placentation (pre-eclampsia and IUGR) and menstrual disorders.
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