Haploinsufficiency for adrenomedullin reduces pinopodes and diminishes uterine receptivity in mice.

Biology of Reproduction
Manyu LiKathleen M Caron

Abstract

Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein-coupled receptor when the receptor, called calcitonin receptor-like receptor (CL), is associated with a receptor activity-modifying protein 2 (RAMP2). We demonstrated previously that haploinsufficieny for each of these genes led to reduced maternal fertility, and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation, and fetal growth. Here, we further demonstrate that Adm(+/-) female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation, or fertilization. The poor fertility of Adm(+/-) female mice could not be rescued by transfer of wild-type blastocysts, which suggested an underlying defect in uterine receptivity. In fact, we found that Adm, Calcrl, and Ramp2 gene expressions are tightly and spatiotemporally regulated in the luminal epithelial cells of the uterus during the estrus cycle and the peri-implantation period. RAMP3, which also generates an AM receptor when associated with CL, had a diametrically opposite expression pattern than that of Adm, Calcrl, and Ramp2 and was most robustly induced in the stroma of the uterus. Fi...Continue Reading

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Citations

Dec 12, 2012·Nature Medicine·Jeeyeon ChaSudhansu K Dey
May 3, 2013·The Journal of Clinical Investigation·Manyu LiKathleen M Caron
Aug 10, 2011·Reproductive Biology and Endocrinology : RB&E·Lei LiFai Tang
Aug 19, 2014·Cellular & Molecular Immunology·Brooke C Matson, Kathleen M Caron
Mar 20, 2012·Trends in Endocrinology and Metabolism : TEM·Patricia M Lenhart, Kathleen M Caron
Apr 13, 2011·American Journal of Reproductive Immunology : AJRI·Angela R Lemons, Rajesh K Naz
Oct 20, 2010·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Anneli Stavreus-EversMargaret C P Rees
Mar 20, 2015·Nature Immunology·Mercy PrabhuDasKoji Yoshinaga
May 12, 2010·American Journal of Reproductive Immunology : AJRI·Koji Yoshinaga
Aug 18, 2018·The Journal of Experimental Medicine·Duncan I MackieKathleen M Caron
Jun 19, 2018·The Journal of Clinical Investigation·Leona MatsumotoYutaka Osuga
Jun 7, 2018·Fertility and Sterility·Brooke C MatsonKathleen M Caron

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Methods Mentioned

BETA
immunoprecipitation
scanning electron microscopy

Software Mentioned

JMP
SAS

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