Evidence for a novel role of Pregnancy-Associated Glycoproteins in maintenance of the bovine CL of pregnancy.

Embryonic interferon-tau (IFNT) suppresses oxytocin-induced endometrial prostaglandin F2a (PGF) pulses, likely involved in maintaining the bovine CL during early pregnancy. After Day 21 of bovine pregnancy, oxytocin-induced PGF pulses are observed, yet luteal persistence continues through unknown mechanisms. Pregnancy-Associated Glycoproteins (PAGs), reported over 40 years ago, increase as IFNT declines, but their physiological role remains undefined. We hypothesized that PAGs prevent CL regression. Holstein heifers were synchronized to ovulate on Day 0. In Study 1 (n = 12), heifers received ipsilateral intrauterine infusions every 48h from Days 14-24: saline (Control, n = 4), low-dose PAGs (0.635 mg, n = 4), or high-dose PAGs (1.3 mg, n = 4). Study 2 (n = 11) characterized natural circulating progesterone (P4) and PAG profiles from Days 14 to 60 in pregnant heifers. Study 3 (n = 25) compared daily ipsilateral (IPSI, n = 8) or contralateral (ContraLat, n = 9) intrauterine infusions of PAGs (2 mg) versus bovine serum albumin control (2 mg, n = 8). Luteal blood flow (color Doppler), plasma P4 (RIA), and PAG concentrations (ELISA) were assessed. Results indicated luteal maintenance by PAGs. In study 1, PAG treatment delayed luteolysis (Day 22 and 23 vs. Day 17 in Control; P < 0.0001). PAG concentrations during natural pregnancy (study 2) far exceeded those achieved by infusion (study 1). In study 3, luteal lifespan was prolonged in IPSI (Day 25) relative to ContraLat (Day 20) PAG infusions or Control (Day 16; P < 0.0001); although, oxytocin increased PGF metabolite (PGFM) in all groups. These results introduce a potential novel, local, intrauterine, anti-luteolytic role for PAGs to maintain the bovine CL of pregnancy.