Complications in pregnancy can arise because of both fetal deficiencies and maternal deficiencies. Previous studies in the Caron laboratory have shown that mouse embryos lacking both copies of the gene encoding a protein known as adrenomedullin (AM) die at embryonic day 14.5 (E14.5). But now, Kathleen Caron and colleagues at the University of North Carolina at Chapel Hill show that female mice expressing reduced levels of the gene encoding AM have severely decreased fertility. It is therefore possible that modest alterations in human expression of the gene encoding AM might have implications for fertility.
In the study, which appears online on September 14 in advance of publication in the October print issue of the Journal of Clinical Investigation, it was shown that female mice with only one copy of the gene encoding AM (AM+/- mice) crossed with wild-type male mice have smaller litters than wild-type female mice crossed with either AM+/- or wild-type male mice. Reduced litter size was associated with fetal-growth restriction and embryo loss at E9.5–E12.5, which is when the placenta develops. Indeed, the placentas of growth-restricted embryos were closely spaced and showed morphologic and histologic defects. This study shows that in female mice a reduction in the level of AM severely decreases their fertility by affecting implantation and placental development, and suggests that in humans a small decrease in AM expression could negatively impact a woman's fertility.
TITLE: Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice
AUTHOR CONTACT: Kathleen M. Caron The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Phone: (919) 966-5215; Fax: (919) 966-5230; E-mail: Kathleen_caron@med.unc.edu .
View the PDF of this article at: https://www.the-jci.org/article.php?id=28462
Journal of Clinical Investigation