Mice that were genetically engineered not to produce the liver receptor homolog-1 (Lrh-1) molecule were unable to create the uterine conditions necessary for establishing and sustaining pregnancy, resulting in the formation of defective placentas. The researchers then showed that Lhr-1 was present in the human uterus and the essential processes related to the success of early gestation.
“We previously showed that Lrh-1 is essential for ovulation. Our newest studies have revealed that it is plays an important role in the uterus, raising the possibility that Lrh-1 deficiency contributes to human gestational failure,” explained lead author Bruce Murphy, of the university’s Animal Reproduction Research Centre. “We worked with mice before looking at human tissues. I believe it premature to propose determination of Lrh-1 in uterine biopsies as a diagnostic tool, but we are working on determining the receptor’s pattern of expression across the menstrual cycle.
The researchers also looked at whether hormone replacement therapy might restore normal uterine functions in the mice. “Progesterone did not make a difference. Although hormone therapy allowed for the embryos to implant, we saw problems with the lining in the uterus, compromised formation of the placenta, fetal growth retardation and fetal death,” Murphy said. “However, there are new Lrh-1 agonists and antagonists, currently in clinical trials to treat hepatic consequences of type II diabetes, and thus therapeutic intervention might be possible.”
The study was published in Nature Medicine on June 30, 2013, and was funded by the Canadian Institutes of Health Research. The US National Institutes of Health funded collaborators at Baylor University that contributed to the study. The University of Montreal is officially known as Université de Montréal.
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University of Montreal (officially Université de Montréal)