The characteristics of placental angiogenesis-related markers in early and late preeclampsia

Abstract

Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and mortality worldwide, accounting for more than 70,000 maternal deaths each year. Of all maternal deaths, 10–15% are directly associated with preeclampsia and its complications. Early-onset preeclampsia (EOP) is usually defined as preeclampsia that develops before 34 weeks of gestation, whereas late-onset preeclampsia (LOP) develops at or after 34 weeks of gestation. Although the presenting features overlap, they are associated with different maternal and fetal outcomes, biochemical markers, heritability, and clinical features. To date, no review has analyzed the data focusing on early- versus late-onset preeclampsia. EOP is the most severe clinical variant of disease occurring 5-20% of all cases of preeclampsia and is associated with neonatal morbidity and mortality. LOP occurring about 75-80% of all cases of preeclampsia; which are associated with maternal morbidity (metabolic syndrome, impaired glucose tolerance, obesity, dyslipidaemia, chronic hypertension), normal birth weight and normal placental volume. In our previous study, EOP was strongly associated with adverse feto-placental conditions and severe complications. The cause of impaired feto-placental function may be the abnormal invasion of trophoblasts and remodeling of the spiral arteries, which can result in limited blood flow and lead to growth restriction and fetal distress symptoms. The aim of the study was an analysis of differences between placental angiogenesis in EOP and LOP. Material and Methods. In the study, women with singleton pregnancy who underwent prenatal assessment at the I-st maternity hospital, Vinnytsya, Ukraine from May 2018 to December 2021 were eligible for inclusion. Our investigation included 40 placentas after delivery among women with preeclampsia (main group) and 40 placentas after physiological delivery in somatically healthy women, who hadn`t complications during pregnancy (control group). Placentas in the main group were divided into two sub-groups (20 in each) – with EOP and LOP. Each group underwent both hystomorphometrical and immunohystochemical investigation with biomarkers CD23, VEGF and PP13. The study was performed at the National Pirogov Memorial Medical University, Vinnytsya, Ukraine, under budget grant No. 0121 U109141. Results PP13 is located in syncitiotrophoblast of the villi of chorion and in multinuclear luminal trophoblast in transformed decidual spiral arterioles. PP13 is secreted by syncitiotrophoblast, and along with decreased levels of expressed PP13 gestational period was complicated by preeclampsia. Positive immunohystochemical reaction to PP13 was determined in all samples of syncitiotrophoblast of villi of chorion. Investigations showed that expression of PP13 in sub-groups with EOP (1.54±0.13 cells in vision (CiV)) and LOP(3.78±0.22 CiV) was a significant lower (p ˂0.001) comparing to control group (7.97±0.64 CiV). Positive immunohistochemical reaction to VEGF was determined in all samples of endothelia of the capillaries of the villi of chorion. Our investigation showed that expression of VEGF in sub-groups with EOP and LOP was a significant lower also (p ˂0.001) comparing to a control group (12.45±0.82 CiV). Expression of CD23 was negative in all samples in endothelia of the capillaries of the villi of chorion and cyncithiotrophoblast among placentas in early (0.18±0.02 CiV) late preeclampsia (0.34±0.04 CiV) and had the same significant authenticity (p ˂0.001), including in relation to data with placenta after physiological pregnancy (0.52±0.05 CiV). Conclusion. During immunohystochemical investigation of placenta of two main groups we found statistically significant decrease in expression of biomarker VEGF, PP13, and CD23 in endothelia of vessels of chorion, that can point out on violation of function of vascular system and increased vascular resistance of placental blood stream. In EOP decreased angiogenesis-related markers in placental tissue was more significant (p<0.001) than in LOP.