Placental expression of HtrA1 in pregnancies complicated by preeclampsia

PREECLAMPSIA FUNMINIYI AJAYI, BRIAN BROST, JEREMY CHIEN, THOMAS GAFFEY, WILLIAM WATSON, Mayo Clinic College of Medicine, Obstetrics and Gynecology, Rochester, Minnesota, Mayo Clinic College of Medicine, Pathology and Laboratory Medicine, Rochester, Minnesota, Mayo Clinic College of Medicine, Anatomic Pathology, Rochester, Minnesota OBJECTIVE: The placenta has a high rate of cell proliferation and undergoes near continuous remodeling with a balance of cell proliferation and death. A serine protease, HtrA1, has been shown to be involved with apoptosis, cellular differentiation, and invasiveness (marked downregulation in several cancers). Placental HtrA1 expression is noted to increase as pregnancy progresses. Preeclampsia is a disorder associated with increased villous/ extravillous trophoblast apoptosis and abnormal cytotrophoblast invasion. An association with preeclampsia and HtrA1 has not been evaluated. We aimed to establish if the expression of HtrA1 is altered in the placenta of preeclamptic women. STUDY DESIGN: Qualitative expression of HtrA1 was assessed by immunohistochemical techniques in archived third trimester placental tissues using gestational age-matched normotensive (n=9) and severe preeclamptic women (n=9). Women delivered at term with mild preeclampsia (n=3) were also evaluated. Expression of HtrA1 was rated by a Placental Pathologist on a scale of 0 (no expression) and 3 (marked expression). RESULTS: Visually, no difference in HtrA1 staining of cytotrophoblasts was noted in normotensive or mild preeclamptic placentas. HtrA1 staining was noted throughout the placenta with slightly higher levels of staining in the extravillous cytotrophoblasts of placentas obtained from patients with severe preeclampsia. Placentas of women with severe preeclampsia showed marked increased staining of the villous cytotrophoblasts compared to control placentas. Staining was noted mainly in the cytoplasm; some nuclear staining was also noted. CONCLUSION: HtrA1 is significantly upregulated in the villous cytotrophoblasts of severe preeclamptic women. The extravillous trophoblasts show a smaller increase in baseline staining. Increased expression of HtrA1 during pregnancy could impair cytotrophoblast invasion, survival, and differentiation resulting in placental dysfuction and fetal compromise. Further research is needed to characterize the role of HtrA1 in the pathophysiology of preeclampsia.