|Vallet, Jeffrey - Jeff|
Submitted to: Theriogenology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2007
Publication Date: 4/20/2007
Citation: Kim, J.G., Vallet, J.L. 2007. Placental expression of the membrane form of folate binding protein during pregnancy in swine. Theriogenology. 67(7):1279-1284.
Interpretive Summary: Previous experiments demonstrated the presence of two different forms of proteins within the uterus during pregnancy that bind folate, a vitamin that is required for protein and DNA synthesis. A soluble, secreted form is produced by the uterine glands up to about day 20 of pregnancy. The other form, a cell membrane receptor form, has been shown to be present in placental tissue beginning between day 20 and 35 of gestation, suggesting that the two forms of folate binding proteins overlap during pregnancy to deliver folate to the developing pig fetus. Although placental production of the membrane form of folate binding protein has been previously reported, the specific cell types within the placenta that were responsible for its production were not known. Our objective was to discover the cell types that produce the membrane form of folate binding protein using a technique called in situ hybridization, which localizes cell types expressing the mRNA for the membrane form of folate binding protein. Our results indicated that only the placental trophoblast epithelium produces detectable levels of mRNA for the membrane form of folate binding protein, and that it is present from day 20 until at least day 105 of pregnancy. These results are consistent with the concept that endometrial gland production of the secreted form of folate binding protein provides delivery of the folate to the developing conceptus until the placenta forms around day 20 of pregnancy, then the placental membrane form of folate binding protein is likely responsible for folate transport throughout the remainder of gestation. The transition period between the two transport mechanisms coincides with a period of pregnancy for which intrauterine crowding is associated with greater fetal deaths, thus the transition from secreted to membrane forms of folate binding protein could contribute to some of the fetal losses that occur due to intrauterine crowding.
Technical Abstract: Previous experiments indicated that secreted (s) and membrane (m) forms of folate binding protein (FBP) are present in the intrauterine environment of the pig. Our studies indicated that the two forms were produced sequentially; the secreted form was present in the intrauterine glands until Day 20 of gestation while binding analysis indicated that placental folate binding increased dramatically in placental membranes until Day 50 of gestation. However, the cell types expressing mFBP have not been investigated. In this experiment, uterine wall sections from Days 20, 35, 50, 70, 90 and 105 of gestation were collected at slaughter and fixed, and subjected to in situ hybridization analysis for mFBP. Silver grains were clearly and uniformly evident over the placental epithelium, including both the tall columnar epithelium at the top of placental folds and the cuboidal epithelium present in the sides and bottom of placental folds. The strength of labeling appeared to be uniform throughout gestation. These results indicate that the placenta expresses mFBP from Day 35 of gestation onward. This expression is consistent with the concept that sFBP and mFBP occur sequentially during gestation in swine, and that placental mFBP expression plays a role in folate transport after the placenta forms between Day 20 and 35 of gestation.