ContentsPre-eclampsia affects 2-8% of pregnant women worldwide and is the third leading cause of maternal mortality in the United States, accounting for 20% of maternal deaths, for which the only known cure is delivery of the placenta. It is known that pre-eclampsia results from defects within the trophoblast invasion of the endometrium and myometrium. At a morphological level within the pre-eclamptic human placenta, trophoblast invasion is shallow, and this results in hypoperfusion, which is a life-threatening condition for both the mother and the foetus. Pre-eclampsia has been intensively investigated for over 50 years, and yet the causes are largely unknown. Despite a large body of data, it is still unknown exactly which mechanisms regulate trophoblast invasion. An effective animal model may be crucial to understanding the underlying causes of pre-eclampsia. A canine model is a proposed improvement on the current efforts to investigate disorders of shallow trophoblast invasion throughout gestation and to improve understanding of the factors that regulate trophoblast invasion. The objectives of this research were to elucidate and compare cellular and molecular similarities between normal canine trophoblasts with those from recently published reports on pre-eclampsia in women.
Contents Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), vascular endothelial growth factor (VEGF)‐A, VEGF‐A receptor (Flt‐1) and KiSS‐1 receptor (KiSS‐1R) all play a role in trophoblast invasion in a number of mammalian species. However, mRNA expression of factors regulating trophoblast invasion has not been studied in dogs. Abnormal expression of these factors at the end of canine gestation may contribute to placental retention and/or subinvolution of placental sites. Therefore, we sought to determine the relative mRNA expression of these factors in canine chorioallantois tissue at 61 ± 1 day past the LH surge (pre‐term; n = 4), following elective c‐section at 64 ± 1 day past the LH surge prior to first‐stage labour (pre‐labour; n = 4) and following natural delivery (parturient; n = 3). Total RNA was isolated, real‐time RT‐PCR was performed, and relative expression was calculated using the relative quantitation (2−ΔΔCT) method. MMP‐9 mRNA expression was significantly higher in pre‐term samples compared to pre‐labour and parturient samples. The results showed no significant difference between MMP‐2, TIMP‐2, VEGF‐A and Flt‐1 mRNA expression among the three groups. KiSS‐1R mRNA was not expressed in any tissues studied. Gene expression of MMP‐9 may be related to the onset of labour, whereas MMP‐2, VEGF‐A, Flt‐1, TIMP‐2 and KiSS‐1R mRNA do not appear to play a role at the end of gestation in the dog.
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