Pregnancy-Associated Bovine and Ovine Glycoproteins Exhibit Spatially and Temporally Distinct Expression Patterns During Pregnancy1

Abstract

The pregnancy-associated glycoproteins (PAG) constitute a large family of recently duplicated genes. They show structural resemblance to pepsin and related aspartic proteinases. A total of 21 bovine (bo) PAG and 9 ovine (ov) PAG cDNA have been identified. Phylogenetic analysis indicated that the PAG are divided into two main groupings that accurately reflect their tissue expression, as determined by in situ hybridization. In the first pattern, represented by ovPAG-2 and boPAG-2, -8, -10, and -11 (where the numbering is arbitrary and reflects order of discovery within species), expression occurred throughout the outer epithelial layer of the placenta (trophectoderm). The second pattern was predominant localization to binucleate cells. Ribonuclease protection assays, which allow discrimination between closely related transcripts, have shown that the expression of PAG varies in a temporal manner over pregnancy. Of those bovine PAG expressed predominantly in binucleate cells, boPAG-1, -6, and -7 are expressed weakly, if at all, by Day 25 placenta, but are present at the middle and end of pregnancy. Others, such as boPAG-4, -5, and -9, are expressed at Day 25 and at earlier stages. Although not among the earliest PAG produced by the trophoblast, boPAG-1 has been used for pregnancy diagnosis, particularly in dairy cows, where there is a major need for a sensitive method capable of detecting pregnancy within 1 mo of conception. It seems likely that some of the newly discovered PAG will be better candidates than PAG-1 for pregnancy diagnosis.

Isolation and characterization of eight pregnancy-associated glycoproteins present at high levels in the ovine placenta between day 60 and day 100 of gestation

“…The PAG identified in this way include ovPAG-1 [2], ovPAG-2 [11], and ovPAG 3 to 9 [12]. In addition, ribonuclease protection assays and in situ hybridization have yielded more information on PAG-family proteins [13]. Firstly, ovPAG-2 appears to be the only PAG expressed on day 13.…”

“…The onset of expression of ovPAG-3, -6, -8, and -9 occurs later in pregnancy. Secondly, PAG fall into two groups: PAG expressed predominantly in binucleate cells (ovPAG-1, -3, -4, -5, -6, -7, -8 and -9) and a PAG (ovPAG-2) whose mRNA is detected throughout the trophectoderm [13]. So far, only one molecule (ovPAG 65 ) of the nine identified cDNA has been successfully column-purified [9].…”

Autoimmunization of ewes against pregnancy-associated glycoproteins does not interfere with the establishment and maintenance of pregnancy

“…In the Ruminantia sub-order, the PAGs are represented by two distinct groupings comprising ancient and modern PAGs -based on the relative times at which they arose during Artiodactyl evolution Green et al, 2000;Hughes et al, 2000). The genes for the former are transcribed in both the trophoblast populations of the ruminant placenta (the mononucleate and the binucleate (BNCs) trophoblasts) Green et al, 2000).…”

“…This feature of the modern/ BNC PAGs has been exploited as the basis for pregnancy diagnosis in cattle and related ruminants. Not surprisingly, the modern PAGs have received the bulk of attention from animal scientists and have been the subject of several biochemical, molecular and functional studies (Del Vecchio et al, 1996;Xie et al, 1997;Green et al, 2000;Hughes et al, 2003;Klisch and Leiser, 2003;Weems et al, 2003;Wooding et al, 2005;Klisch et al, 2008). However, despite such efforts, the functional role of the PAGs remains a mystery.…”

“…Clearly, the role of PAGs is uncertain and complicated by the fact that there are so many of them Green et al, 2000;Brandt et al, 2007). A further difficulty in understanding how they operate arises from the fact that nearly all earlier functional studies have been performed in vitro rather than on intact animals.…”