Activation of CCL20 and its receptor CCR6 promotes endometrium preparation for implantation and placenta development during the early pregnancy period in pigs. (March 2019) - Park, Chanho
Abstract: The success of implantation and placentation during early pregnancy depends on the intrauterine environment of diverse histotrophs, including nutrients, growth factors, cytokines, and chemokines. Here, we determined the functional role and signal transduction of CC-motif chemokine 20 (CCL20) in the porcine endometrium during pregnancy. The expression of CCL20 and its receptor CCR6 was abundant in the glandular epithelium (GE) and luminal epithelium (LE) of the porcine endometrium during early pregnancy. Administration of CCL20 to porcine endometrial LE cells increased cellular proliferation with strong PCNA expression by activation of PI3K and MAPK signaling. Blocking PI3K and MAPK decreased the CCL20-mediated elevated proliferation of pLE cells. Moreover, the proliferation of pLE cells was enhanced by inhibiting the LPS-induced cytokines and tunicamycin-induced endoplasmic reticulum (ER) stress response proteins. Overall, these results suggest that CCL20 may improve the endometrial receptivity through inducing proliferative signal transduction in the porcine endometrium during the early gestational period. Highlights: CCL20-CCR6 system is up-regulated in the uterine endometrium during early pregnancy. CCL20 induces the proliferation and cell cycle progression of pLE cells. CCL20 activates intracellular signaling pathways including PI3K and MAPK. CCL20 reduces tunicamycin-induced ER stress in pLE cells. CCL20-CCR6 is important for development of the endometrium during early pregnancy.