Effects of long-term progesterone on developmental and functional aspects of porcine uterine epithelia and vasculature: progesterone alone does not support development of uterine glands comparable to that of pregnancy

Abstract

In pigs, endometrial functions are regulated primarily by progesterone and placental factors including estrogen. Progesterone levels are high throughout pregnancy to stimulate and maintain secretion of histotroph from uterine epithelia necessary for growth, implantation, placentation, and development of the conceptus (embryo and its extra-embryonic membranes). This study determined effects of longterm progesterone on development and histoarchitecture of endometrial luminal epithelium (LE), glandular epithelium (GE), and vasculature in pigs. Pigs were ovariectomized during diestrus (day 12), and then received daily injections of either corn oil or progesterone for 28 days. Prolonged progesterone treatment resulted in increased weight and length of the uterine horns, and thickness of the endometrium and myometrium. Hyperplasia and hypertrophy of GE were not evident, but LE cell height increased, suggesting elevated secretory activity. Although GE development was deficient, progesterone supported increased endometrial angiogenesis comparable to that of pregnancy. Progesterone also supported alterations to the apical and basolateral domains of LE and GE. Dolichos biflorus agglutinin lectin binding and a v integrin were downregulated at the apical surfaces of LE and GE. Claudin-4, a 2 b 1 integrin, and vimentin were increased at basolateral surfaces, whereas occludins-1 and -2, claudin-3, and E-cadherin were unaffected by progesterone treatment indicating structurally competent trans-epithelial adhesion and tight junctional complexes. Collectively, the results suggest that progesterone affects LE, GE, and vascular development and histoarchitecture, but in the absence of ovarian or placental factors, it does not support development of GE comparable to pregnancy. Furthermore, LE and vascular development are highly responsive to the effects of progesterone.

Expression of mesenchymal-related genes by the bovine trophectoderm following conceptus attachment to the endometrial epithelium

“…Since the bovine trophoblast cells from mid-gestational placentomes do not express VIM , this coexistence of the epithelial and mesenchymal gene expression in the trophectoderm could be transient and possibly be a prerequisite for the steps from attachment to adhesion. Recently, coexpression of cytokeratin and VIM was also found in the luminal epithelium of long-term progesteronetreated pigs (Bailey et al 2010). It has been noted that many processes occurring during development and tissue remodeling, as well as in adult organisms, involve a transient loss of epithelial polarity without full acquisition of mesenchymal characteristics.…”

Soy isoflavones improves endometrial barrier through tight junction gene expression

“…In porcine uterine tissues, the mRNA expression of TJ proteins has been detected (Bailey et al 2010, Samborski et al 2013. The expression of claudin-1, -2, -3 and -4 proteins are dynamic through the estrous cycle or pregnancy under the regulation of ovarian sex steroids and placental factors, i.e., estrogen, progesterone, and prolactin (Bailey et al 2010).…”

“…The expression of claudin-1, -2, -3 and -4 proteins are dynamic through the estrous cycle or pregnancy under the regulation of ovarian sex steroids and placental factors, i.e., estrogen, progesterone, and prolactin (Bailey et al 2010). We, therefore, further studied whether the changes in TER may be relevant to the genomic effects of Ge and Di on the transcription level of claudin and ZO1.…”

“…Other study has shown the upregulation of claudin-4 but not claudin-3 in surface and glandular epithelia in response to progesterone level (Bailey et al 2010). As Ge and Di has an affinity for ERs to produce an estrogenic activity, these isoflavones may regulate transcription of ER-target genes via the estrogenresponsive elements (EREs) present within the gene promoter regions.…”

“…TJ proteins are regulated by sex steroid hormones, particularly estrogen and progesterone (Satterfield et al 2007, Bailey et al 2010. Isoflavonoids, a class of phytoestrogens mainly found in soy-based foods, which have been evidenced for both estrogenic and antiestrogenic actions, may modify the TJ barrier expression and function (Brooks & Skafar 2004, Rietjens et al 2013.…”