Cathepsin B, Cathepsin L, and Cystatin C in the Porcine Uterus and Placenta: Potential Roles in Endometrial/Placental Remodeling and in Fluid-Phase Transport of Proteins Secreted by Uterine Epithelia Across Placental Areolae1

Abstract

Cathepsins (CTSB and CTSL1) and their inhibitor, cystatin C (CST3), remodel uterine endometrium and placenta for transport of gases, micronutrients, and macromolecules essential for development and growth of the conceptus (embryo/fetus and placental membranes). We examined the temporal/spatial control of expression for CTSB, CTSL1, and CST3 mRNAs in endometria and placentae of pigs using three developmental models: 1) pigs were hysterectomized during the estrous cycle or pregnancy; 2) cyclic pigs were injected with estrogen to induce pseudopregnancy and were hysterectomized; and 3) pigs were ovariectomized, injected with progesterone, and hysterectomized. The abundance of CTSB, CTSL1, and CST3 mRNAs increased in endometrial epithelia during pregnancy and in response to exogenous progesterone but not estrogen. CST3 was also expressed in cells scattered within the stratum compactum stroma. Progesterone decreased epithelial but increased stromal compartment expression of CST3. CTSB increased in all chorionic epithelia, but CTSL1 was limited to chorionic epithelia that form areolae to absorb secretions from uterine glands. Based on the placental and endometrial distribution of CTSL1, we examined expression in the neonatal enterocytes known to transport immunoglobulins from colostrum. CTSL1 was also expressed in enterocytes of intestine from neonatal piglets. Therefore, CTSL1 is expressed by endometrial epithelia, placental areolae, and neonatal intestine, and it may function in the transport of macromolecules across these epithelia. Our results support the idea that reciprocal interactions between CSTL1, CTSB, and CST3 may be required to remodel endometrial and placental tissues for close apposition between maternal and fetal vasculatures and to facilitate transplacental transport of gases, micronutrients (amino acids, glucose), and macromolecules (proteins). Cysteine proteases and their inhibitors may also specifically modify proteins for successful utilization and fluid-phase transport across uterine, placental, and neonatal gut epithelia.

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

“…Although there were more total GE cells in uteri of progesterone-treated gilts than CO-treated gilts, due to increased uterine horn length and endometrial thickness, GE branching and coiling as they extended into the uterine wall were insufficient to maintain GE density. Indeed, GE number and size did not approach levels normally observed on day 40 of pregnancy (Garlow et al 2002, Song et al 2009, 2010. This is in contrast to the vasculature of the uterus, which increased in proportion to the thickness of the uterine wall in shallow regions of the endometrium, and significantly increased in density in the deep endometrium of progesterone-treated pigs compared with CO-treated pigs.…”

“…2). These LE cells exhibited secretory function because immunoreactive cathepsin B (CTSB), a protease expressed and secreted from the LE of pregnant pigs (Song et al 2010), was detected in the uterine flushings of progesterone-treated pigs (Fig. 2C).…”

Hic-5 mediates endothelial sprout initiation by regulating a key surface metalloproteinase

“…Slides were counterstained with Prolong Gold Antifade reagent with DAPI (Life Technologies, Grand Island, NY; 1:500) and coverslips were added. For in vivo studies, samples were used from a previously conducted study (Song et al, 2010). Sexually mature gilts of similar age, weight and genetic background (F1 crosses of Yorkshire X Landrace sows and Duroc X Hampshire boars) were observed daily for estrus (day 0) and exhibited at least two estrus cycles of normal duration (18 to 21 days) before being used in these studies.…”

Expression of Heparanase Is Associated with Breed-Specific Morphological Characters of Placental Folded Bilayer Between Yorkshire and Meishan Pigs1

“…Vallet et al [3] recently concluded that an increased placental function is one of the important contributors to higher prenatal survival in pigs. A primary function of the placenta is the transfer of oxygen, nutrients, and waste [4,5]. The efficiency of the nutrient transfer from the maternal to fetal systems affects the development of the fetus and thus influences prenatal survival in pigs.…”