Placental lesions and differential expression of pro-and anti-angiogenic growth mediators and oxidative DNA damage marker in placentae of Ghanaian suboptimal and optimal health status pregnant women who later developed preeclampsia.

Abstract

BackgroundAngiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in these factors contribute to pre-eclampsia (PE). Suboptimal health status (SHS), an intermediate between health and disease, has been associated with imbalanced AGMs and OS biomarkers. Thus, SHS pregnant women may be at increased risk of developing PE and may present abnormal placental alteration and expression of AGMs and OS compared to optimal health status (OHS) pregnant women. We examined the histopathological morphology, immunohistochemical expression of AGMs antibodies and oxidative DNA damage marker in the placentae of SHS and OHS pregnant women who developed early-onset PE (EO-PE) and late-onset (LO-PE) compared to normotensive pregnancy (NTN-P).MethodsThis nested case-control study recruited 593 singleton normotensive pregnant women at baseline (10-20 weeks gestation) from the Ghanaian Suboptimal Health Status Cohort Study (GHOACS) undertaken at the Komfo Anokye Teaching Hospital, Ghana. Socio-demographic, clinical and obstetrics data were collected, and a validated SHS questionnaire-25 (SHSQ-25) was used in classifying participants into SHS (n = 297) and OHS (n = 296). Participants were followed until the time of PE diagnosis and delivery (32-42 weeks gestation). Blood samples were collected at the two-time points and were assayed for AGMs; soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PIGF), vascular endothelial growth factor-A (VEGF-A), and soluble endoglin (sEng), and OS biomarkers; 8-hydroxydeoxyguanosine (8-OHdG), 8-epiprostaglandinF2-alpha (8- epi-PGF2α) and total antioxidant capacity (TAC) using ELISA. Placental samples were collected for histopathological and immunohistochemical analysis.ResultsOf the 593 pregnant women, 498 comprising 248 SHS and 250 OHS women returned for delivery and were included in the final analysis. Of the 248 SHS women, 56, 97 and 95 developed EO-PE, LO-PE and NTN-P, respectively, whereas 14, 30 and 206 of the 250 OHS mothers developed EO-PE, LO-PE and NTN-P, respectively. At baseline, SHS_NTN pregnant women had a significant imbalance in AGMs and OS biomarkers compared to OHS_NTN pregnant women (pLO-PE) more than OHS groups who developed PE (EO-PE>LO-PE) when all were compared to NTN-P (pLO-PE more than OHS- pregnant women who developed EO-PE>LO-PE when all were compared to NTN-P (pConclusionIncreased lesions, oxidative DNA damage, and imbalanced expression between pro-and anti-AGMs are associated more with SHS-embodied PE placentae rather than OHS-embodied PE subtypes, thus potentially allowing differential evaluation of PE.