Secreted and Placental Membrane Forms of Folate-Binding Protein Occur Sequentially During Pregnancy in Swine1

Abstract

The objective was to understand how two forms of folate-binding protein interact to accomplish folate transport during pregnancy in swine. Specific folate binding was measured in uterine flushings during the estrous cycle and early pregnancy and in allantoic fluid (secreted form) and placental membranes (membrane form) throughout later pregnancy. In addition, the localization of the secreted form of folate-binding protein (sFBP) in uterine wall sections was assessed. Uterine flushings were collected on Days 10, 13, and 15 of the estrous cycle and pregnancy. Allantoic fluid and placentas were collected on Days 20, 35, 50, 70, 90, and 105 of pregnancy. Uterine-wall sections were collected on all days of the experiment. Folate binding was measured by incubation of aliquots of uterine flushings, allantoic fluid, or placental microsomal membranes with 0.5-4 nM [(3)H]folate. Uterine-wall sections were incubated with purified anti-FBP IgG or normal rabbit serum IgG to localize sFBP. Folate binding did not differ between early pregnancy and the estrous cycle in uterine flushings, was greatest from Day 50 to 70 of pregnancy in allantoic fluid, and was greatest from Day 50 of pregnancy onward in placental microsomal membranes. Staining for sFBP was present in the endometrial glands from Day 10 to 15 in cyclic gilts and from Day 10 to 20 in pregnant gilts. The pattern of folate binding and sFBP staining supports the concept that sFBP transports folate to the developing conceptus until placentation and then the placental form takes over folate transport.

Placental expression of the membrane form of folate binding protein during pregnancy in swine

“…In more recent studies, it was reported that the two forms were produced sequentially during the 114-d gestation of the pig. The sFBP form increased dramatically in uterine flushings at the time of conceptus elongation (Day [11][12][13][14][15] and was present in the intrauterine glands until Day 20 of gestation [7,10]. We have demonstrated that genetic polymorphisms in the sFBP gene were associated with differences in uterine capacity, but not litter size, because of simultaneous effects on ovulation rate [11].…”

Paradigm of Time-sequence Development of the Intestine of Suckling Piglets with Microarray

“…Among these genes, CN161469 was found to be similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), which suggests that it possesses the similar biological functions. In addition, the gene U89949.1, which encodes a folate binding protein that is involved in the transport of foliate (Vallet et al, 2001; Kim and Vallet, 2004), played an major role in the network. This finding was in accordance with the results of the assessment of the GO categories and pathway analysis.…”

The Mechanism of Carrier-Mediated Transport of Folates in BeWo Cells: The Involvement of Heme Carrier Protein 1 in Placental Folate Transport

“…There have been several studies on folate transport mechanisms using placental cell lines or mammalian placenta. 24,25) FR, which transports folates by endocytosis, and RFC, which mediates bidirectional folate transport, are thought to be involved in the folate transport mechanisms in the placenta, but Keating et al have suggested that other carriers, which differ from both FR and RFC, are also involved in folate transport under an acidic condition in BeWo cells. 26) Hence it has been suggested that there are more than two transport mechanisms in folate transport in the placenta, and further investigation is necessary to clarify these complex mechanisms.…”