Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo.

The regulation of human implantation is still unknown. Evidence derived from experiments in vitro and from animal systems suggest a direct impact of the embryo on endometrial differentiation and the implantation process itself. Being one of the earliest embryonic products, hCG may be a key mediator of this embryo-maternal communication. Using a multiplex nested rT-PCR approach we have been able to demonstrate the presence of full-length and truncated hCG/LH-receptor mRNA in human endometrium and in decidua. The expression of functional receptors appears to be cycle-dependent and regulated by changes in the alternative splicing pattern. To investigate possible direct effects of hCG on endometrial paracrinology in the human female in vivo, we have developed an intrauterine microdialysis system that allows the continuous sampling from the uterine cavity over several hours as well as the application of exogenous hCG and the monitoring of the tissue response to this stimulus. HCG administration during the secretory phase significantly modulated several endometrial paracrine parameters that correlate to endometrial differentiation (IGFBP-1), angiogenesis (VEGF), implantation (LIF, M-CSF) and tissue remodelling (MMP-9). In summary, intrauterine microdialysis is a novel tool for the clinical assessment of endometrial paracrinology in vivo. HCG appears to directly modulate endometrial differentiation and function in humans.