Time-dependent changes in pregnancy-associated glycoproteins and progesterone in commercial crossbred sheep

Abstract

The ruminant placenta functions as an endocrine and paracrine organ secreting proteins, growth factors, and steroid hormones, including pregnancy-associated glycoproteins (PAG), proteins with elusive function, which are readily detectable in maternal serum after placental attachment. In sheep, circulating progesterone beyond gestational Day 50 is predominantly of placental origin. The relationship among placental secreted factors, including progesterone, remains uncertain in sheep. The first aim of the study was to determine the relationship between gestational PAG profiles—using two commercial ELISA assays—progesterone, and fetal growth during pregnancy. The second aim of the study was to assess the presence and clearance of PAG in neonatal lambs and peripartum ewes in commercial crossbred sheep. Maternal serum samples were collected during mid-pregnancy and assayed for PAG1, pregnancy-specific protein B (PSPB), and progesterone. Maternal serum samples were also collected weekly starting 1-month prepartum until 10 weeks postpartum. Serum samples from newborns were collected at birth until Day 12 after birth and assayed for PAG1. Circulating maternal PAG1 concentrations steadily increased throughout mid-gestation, whereas PSPB exhibited a bimodal pattern of secretion. A strong positive correlation was observed between progesterone and PAG1 (r2 = 0.779, P < 0.0001), but not between PSPB and progesterone. No relationship was found between placental factors (PAG1, PSPB, and progesterone) and fetal size. PAG1 concentrations were lower before and after parturition in singleton compared with twin pregnancies (P < 0.05). Maternal PAG1 concentrations began declining at parturition and continued to decline until 10 weeks after parturition (P < 0.05). In newborns, PAG1 concentrations continuously declined in both singleton and twins regardless of sex (P < 0.05) and cleared from newborn serum by 12 days after birth. Our findings reported for the first time how different assays used to determine circulating PAG concentrations display different gestational profiles in sheep and how it allows the differentiation between singleton and multiple pregnancies. In conclusion, the strong correlation between PAG1 and progesterone during gestation reports that PAG1 can be effectively used as a marker of placental function.