Expression of corticotrophin-releasing hormone in the mouse uterus: participation in embryo implantation

The detection of corticotropin-releasing hormone (CRH) in the pregnant and non-pregnant uterus has driven research to determine the role of this 41 am ino acid neuropeptide in the female reproductive system. As concentrations of CRH mRNA and its peptide product are greater in the implantation sites o f the early pregnant uterus compared with the regions between implantation sites, CRH has been hypothesised to participate in blastocyst implantation. Using the mouse system as an experimental model, we studied the distributi on of CRH in the uterus during the oestrus cycle and early gestational peri od, and now provide evidence for its involvement in embryo implantation usi ng cell culture techniques. The percentage of CRH-pssitive uterine cells an d the amount of CRH released during anoestrus, pro-oestrus and oestrus were determined by immunofluorescence and ELISA experiments respectively. The h ighest number of intracellularly CRH-positive cells was obtained during pro -oestrus, whereas the highest CRH concentration in uterine cell culture sup ernatants was detected during anoestrus. At early stages of gestation, CRH was detected in the endometrium on days 2, 3 and 4 of pregnancy and in the myometrium on days 3 and 4, whereas it was undetectable on day 5. The funct ional role of CRH during early gestation was evaluated by administering ant i-CRH antibody to mice from day 3 to day 8 of pregnancy. This treatment res ulted in implantation failure in 60% of the cases, in which implantation si tes, although clearly present in the uterus, had failed to host an embryo. These results provide direct evidence about the involvement of CRH in murin e embryo implantation and are in agreement with hypotheses postulated in hu mans.