Adrenomedullin improves fertility and promotes pinopodes and cell junctions in the peri-implantation endometrium.

Autor:	Matson BC; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Pierce SL; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Espenschied ST; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Holle E; Animal Models Core Facility, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Sweatt IH; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Davis ES; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Cystic Fibrosis Center/Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Tarran R; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Cystic Fibrosis Center/Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Young SL; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Kohout TA; Ferring Research Institute Inc., San Diego, California, USA., van Duin M; Ferring Research Institute Inc., San Diego, California, USA., Caron KM; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	Biology of reproduction [Biol Reprod] 2017 Sep 01; Vol. 97 (3), pp. 466-477.
DOI:	10.1093/biolre/iox101
Abstrakt:	Implantation is a complex event demanding contributions from both embryo and endometrium. Despite advances in assisted reproduction, endometrial receptivity defects persist as a barrier to successful implantation in women with infertility. We previously demonstrated that maternal haploinsufficiency for the endocrine peptide adrenomedullin (AM) in mice confers a subfertility phenotype characterized by defective uterine receptivity and sparse epithelial pinopode coverage. The strong link between AM and implantation suggested the compelling hypothesis that administration of AM prior to implantation may improve fertility, protect against pregnancy complications, and ultimately lead to better maternal and fetal outcomes. Here, we demonstrate that intrauterine delivery of AM prior to blastocyst transfer improves the embryo implantation rate and spacing within the uterus. We then use genetic decrease-of-function and pharmacologic gain-of-function mouse models to identify potential mechanisms by which AM confers enhanced implantation success. In epithelium, we find that AM accelerates the kinetics of pinopode formation and water transport and that, in stroma, AM promotes connexin 43 expression, gap junction communication, and barrier integrity of the primary decidual zone. Ultimately, our findings advance our understanding of the contributions of AM to uterine receptivity and suggest potential broad use for AM as therapy to encourage healthy embryo implantation, for example, in combination with in vitro fertilization. (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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