937 Adrenomedullin regulates trophoblast invasion at the uterine-placental interface and is critical for successful pregnancy

Background: Adrenomedullin (ADM) is a vasoactive peptide hormone found in adrenal medulla, central nervous system, immune cells, and muscle, expressed the uterus placenta. ADM plays important roles angiogenesis, vasodilation, inflammation. Altered levels of have been implicated adverse pregnancy outcomes like fetal growth restriction pre-eclampsia. Animal models can be useful tools for examining pathophysiology. Much what known about has learned from mouse model; however, rat superior model human placentation due to deep hemochorial invasion. Objective: We aim explore role at maternal-placental interface characterize wild type null pregnancy. was localized within site by situ hybridization. used Crispr-Cas9-mediated genome editing create mutant Adm knockout rat. The mutation targeted Exon 2 introduced premature stop codon, resulting 206 bp deletion truncated, nonfunctional protein. Germline transmission confirmed. Heterozygous intercrosses failed produce live rats. heterozygous pairs were bred examine placental growth, development, demise through gestation. placentas/fetuses viable gestation day (gd) 13.5, but all had demised or resorbed gd 16.5. Growth evident 13.5 fetuses. Many conceptus demonstrated fetal-placental hemorrhage infarct. On microscopic evaluation, some deficient sites intrauterine trophoblast giant cells decidual early deficiency disrupts invasion uterine-placental Loss results abnormalities placentation, restriction, death Thus, critical successful favorable outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)