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Spatio-temporal expression pattern of progranulin in embryo implantation and placenta formation suggests a role in cell proliferation, remodelling and angiogenesis.

J Desmarais, Faculte de medecine veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada
M Cao, Department of Medicine, McGill University, Montreal, Quebec, Canada
A Bateman, Department of Medicine, McGill University, Montreal, Quebec, Canada
B Murphy, Faculte de medecine veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada

Correspondence: Joelle Desmarais, Email: joelle.desmarais{at}umontreal.ca

Abstract

Embryo implantation in the mink is preceded by a variable but obligate period of delay in development. Under the influence of progesterone and unknown luteal factors, the mink embryo implants 11-13 days following its exit from diapause. Recent work suggests that progranulin, a growth factor and secreted glycoprotein, is involved in trophoblast proliferation, placental development and endometrial differentiation in the mouse. Using the mink model of delayed implantation and endotheliochorial placentation, we examined the spatio-temporal distribution of progranulin in trophoblast and endometrium during pre- and early post-implantation gestation in vivo. A partial sequence of the mink progranulin gene was cloned and sequenced. Comparative sequence analysis revealed that exons 1 and 2 of mink progranulin share 86.6 %, 82.4%, 94.9% nucleic acid sequence identity with the human, mouse and dog sequences respectively, and indicated that the invariable residues of the cysteine-rich motifs of progranulin are well conserved in the mink sequence. By in situ hybridization, we show that mink progranulin transcript is present in the cytotrophoblast and in epithelial and stromal endometrial cells at the site of implantation and during early placental formation. Immunohistochemistry revealed the progranulin protein to be strongly expressed in endometrial luminal and glandular epithelium around the time of implantation. In the incipient labyrinth, progranulin expression is localised to cytotrophoblasts, fetal capillaries, as well as to the hypertrophied maternal endothelial cells. This study demonstrates that high levels of progranulin expression correspond to active cell proliferation, remodelling and angiogenesis occurring during the establishment of the placenta in the mink.