Discussion

Aims: Preimplantation factor (PIF), secreted only by viable mammalian embryos is essential for achieving maternal immune- tolerance without immune-suppression. In human endometrium PIF coordinates and supports implantation and modulates immunity. Transposed to nonpregnant models, PIF displays immune-control and regenerative features in neuroinflammation and diabetes. The aim was to test the hypothesis that PIF exerts anti-inflammatory properties towards equine endometrium challenged with Escherichia coli-derived lipopolysaccharide (LPS) using an established endometrial explant culture model of uterine inflammation. Methods: Luteal (n = 4) and anoestrus (n = 8) stage endometrium was collected from slaughtered mares. Explants were cultured in triplicate in serum-free medium alone (control) and with 0 - 1000 nmol/l sPIF (25 - 100 nmol/l = human physiologic dose) and plus/minus LPS (3 mircogram/ml). Media samples were collected at 24 and 72 h and prostaglandin F2alpha (PGF 2alpha) secreted pyridinoline were measured monthly from 1 - 3 months gestation through to 4 months post foaling, in a group of 18 Thoroughbred, Standardbred and Stockhorse broodmares, using Quidel MicroVue Osteocalcin and PYD assay kits (www.quidel.com). Osteocalcin was measured monthly in foals from 1 - 4 months of age. Changes in bone biomarkers were modelled using general linear models. Results: In mares, mean serum osteocalcin levels decreased from 17.8 (95%CI: 14.9 - 20.7) ng/ml at 34 days gestation to 9.2 (7.6 - 10.5) ng/ml at 320 days (P<0.001 for regression coefficient). Pyridinoline increased from 2.5 (95%CI:1.9 - 3.0) nmol/l at 34 days to 3.2 (3.0 - 3.5) nmol/l at 301 days (P = 0.03 for regression coefficient). Osteocalcin increased 2 months post foaling with a contemporaneous decrease in serum pyridinoline. In foals, osteocalcin levels varied in a nonlinear fashion, increasing rapidly after birth to a peak of 122.1 (95%CI: 97.0 - 147.3) ng/ml at 2 months of age, decreasing by 3 - 4 months. Conclusions: Over gestation, bone accretion decreases and resorption increases in mares, suggesting maternal bone mobilisation to meet fetal demands. The reverse pattern post foaling suggests replenishment of maternal calcium stores. Practical significance: Maternal, fetal and neonatal bone metabolism are coupled. The gestational milieu is likely to influence bone characteristics in the foal, and subsequent future performance. Acknowledgements: Supported by a University of Queensland New Staff Start-up Grant. The authors thank the staff of the UQ Gatton Equine Unit for assistance with conduct of the study.