Paracrine control of uterine differentiation and implantation
HN Jabbour1, HOD Critchley2 & O Gubbay1
The successful establishment of pregnancy is dependent on appropriate embryo development and uterine receptivity. The latter consists of secretory transformation of the glandular epithelial cells followed by decidualisation of the stromal compartment. This phase of the cycle is also characterised by extensive tissue remodelling in the superficial layer of the endometrium in preparation for the invasion and implantation of the proliferating trophoblast cells. Ovarian steroids are known to play a crucial role in the development of a differentiated endometrium capable of supporting implantation. However, many lines of evidence suggest that other locally produced molecules act in an autrocrine/paracrine manner to prepare the endometrium for implantation. The regulation of local events critical for decidualisation and tissue remodelling in normal implantation remain poorly defined. However, only with this information will progress be possible in the management of situations where these physiological events are dysfunctional, such as impaired pregnancy establishment and loss. One key molecule that may regulate many functions in the process of implantation is prolactin. Prolactin is secreted by the decidualised endometrium at the time of predicted conception and in the event of pregnancy local expression/secretion of prolactin persists until term. Prolactin mediates its effects on target cells through interaction with single-pass transmembrane receptors, which belong to the family of cytokine receptors. Localisation of the sites of expression of prolactin and its receptor within the endometrium confirm a paracrine role for this cytokine with effects mediated on different cellular compartments including natural killer cells and the invading trophoblast. Moreover, prolactin is known to induce an array of intracellular responses in the endometrium and this is predicted to confer the pleiotropic effects of the cytokine on target cells. These effects may include regulation of cellular proliferation/differentiation, angiogenesis and modulation of the local immune environment at the utero-placental interface.