S. W. Ricketts

Dynamics of activities of matrix metalloproteinases-9 and -2, and the tissue inhibitors of MMPs in fetal fluid compartments during gestation and at parturition in the mare

During late gestation in the mare, rapid fetal growth is accompanied by considerable placental growth and further invasion of the endometrium by microvilli. This growth requires extensive remodeling of the extracellular matrix (ECM). In early pregnancy, we know that matrix metalloproteinase (MMP)-9 and -2 are involved in the endometrial invasion during endometrial cup formation. The present study investigated whether MMPs are found in fetal fluids later in gestation and during parturition, and if there was a difference in their activities between normal and preterm delivery. Amniotic fluids were collected from pony mares during the latter half of gestation, and amniotic and allantoic fluids from pony and thoroughbred mares at foaling. The fluids were analysed for the activity of MMP-9 and -2, and TIMPs using zymography techniques. There was an increase (P = 0.002) in activity of latent MMP-9 when approaching normal foaling, and a decrease (P < 0.001) during foaling. MMP-2 activity did not change through gestation, or during foaling. When comparing samples from pregnancies resulting in preterm deliveries with samples from foaling mares, the activity of MMP-9 was lower (P < 0.001) and MMP-2 activity was higher (P = 0.004) during foaling than preceding preterm delivery. The activity of MMP-9 was lower (P = 0.002) prior to preterm delivery than before delivery of a live foal at term, whereas no difference (P = 0.07) was demonstrated for latent MMP-2 activity when comparing the same groups. The activity of TIMP-2 was higher (P < 0.001) in the pre-parturient period before normal foaling than preceding preterm delivery. These results suggest that MMPs may have a role as markers for high risk pregnancy in the mare.

Matrix metalloproteinases 2 and 9 in equine amniotic fluid and placental tissues during the last trimester and at parturition

The process of parturition involves a sequence of events that require extensive tissue remodelling. These events include foetal membrane rupture, placental detachment and post-partum involution of the uterus. Normally, foaling in the mare is a quick and dynamic process. Precisely orchestrated tissue remodelling mechanisms are required to control these fast events, hereunder the rupture of the foetal membranes and detachment of the placenta. In tissue remodelling, the matrix metalloproteinases (MMPs) are a much-studied family of enzymes that are involved in extracellular matrix (ECM) degradation. In the mare, invasive chorionic girdle cells have been found to produce MMP-2 and MMP-9, a likely event in the establishment of endometrial cup tissue [1]. The levels of MMP-9 in human and rodent foetal membranes and fluids increased markedly with the onset of labour, relating this enzyme with the rupture of foetal membranes and detachment from the uterus [2]. It is not known whether MMP activity is increased in late gestation or at parturition in mares. The aim of this study was to illustrate the secretion and localisation of MMP-9 and -2 in equine amniotic fluid during late pregnancy and foaling.