# Mitochondrial Dysfunction Combined with Elevated CoQ10 Levels Specifically in Placental Cytotrophoblasts Suggests a Role for Mitophagy in Preeclampsia

## TL;DR

The study finds that mitochondrial dysfunction and increased CoQ10 levels in placental cytotrophoblasts may be linked to preeclampsia, suggesting a role for mitophagy in this pregnancy disorder.

## Contribution

The study identifies cytotrophoblast-specific mitochondrial dysfunction and CoQ10 elevation in preeclampsia, suggesting a novel role for mitophagy in this cell type.

## Key findings

- Preeclampsia is associated with mitochondrial dysfunction in cytotrophoblasts, marked by reduced mtDNA and citrate synthase activity.
- Cytotrophoblasts show elevated CoQ10 levels and signs of mitophagy activation, unlike syncytiotrophoblasts.
- These changes suggest cytotrophoblasts may be more vulnerable in preeclampsia and trigger compensatory mechanisms.

## Abstract

Preeclampsia is a severe pregnancy disorder associated with significant morbidity and mortality for both the mother and the baby. The causes underlying the development of preeclampsia remain unknown, but it is well established that the placenta is the organ that triggers the disease and that its mitochondrial metabolism is compromised. This study suggests that the cytotrophoblast is a placental cell type that is particularly affected at the mitochondrial level in preeclampsia. This mitochondrial dysfunction observed in this cell type is accompanied by an increase in coenzyme Q10 levels, which may represent a compensatory response. The data also suggest the activation of a second potential adaptive mechanism in cytotrophoblasts in response to mitochondrial dysfunction—mitophagy. This alteration and putative compensatory response were not observed in syncytiotrophoblasts. These findings highlight the possible specific involvement of the cytotrophoblast during preeclampsia, a cell type characterized by high mitochondrial activity within the placenta. Overall, these observations support the relevance of cytotrophoblast mitochondrial metabolism for future mechanistic studies aimed at better understanding preeclampsia.

Preeclampsia is a serious pregnancy disorder of unknown etiology. One of its cellular hallmarks is increased mitochondrial dysfunction in placental tissue. Further investigation into this aspect may help elucidate the molecular basis of preeclampsia. A total of 24 pregnant women who delivered by cesarean section participated in the study: n = 13 controls and n = 11 diagnosed with preeclampsia. Maternal blood samples were collected to assess the biochemical profile, and demographic and clinical data were recorded. Placental trophoblast samples were processed to isolate mitochondria and perform molecular biology assays. Women with preeclampsia exhibited the characteristic clinical features of the disease, along with biochemical alterations consistent with an inflammatory process. A significant decrease (73%) in mitochondrial DNA (mtDNA) copy number in trophoblastic tissue and a reduction in citrate synthase (CS) activity (−51%) in cytotrophoblast mitochondria-enriched fractions were observed in preeclampsia, indicating mitochondrial dysfunction accompanied by a loss of functional mitochondrial mass. In addition, we detected a marked decrease in MnSOD levels (−32%), together with an increase in the LC3II/LC3I ratio (47%) in cytotrophoblast mitochondria-enriched fractions, supporting the presence of mitochondrial alterations and suggesting the possible activation of mitophagy specifically in this cell type. Moreover, coenzyme Q10 (CoQ10) levels were elevated by 31% in trophoblastic villi. A pronounced 2.5-fold increase in CoQ10 normalized to CS activity (CoQ10/CS) was detected specifically in cytotrophoblasts from preeclamptic placentas. Importantly, we did not observe these alterations in the syncytiotrophoblast. In conclusion, preeclampsia is associated with mitochondrial dysfunction and increased CoQ10 levels normalized to CS activity, specifically in cytotrophoblast mitochondria, with findings being consistent with a possible involvement of mitophagy in this cell type. These findings suggest that cytotrophoblast mitochondrial metabolism may be more affected in preeclampsia compared with syncytiotrophoblasts, and that CoQ10 accumulation together with the possible activation of mitophagy may represent cellular defense mechanisms. Due to the limitations of the study, it should be considered exploratory and hypothesis-generating, and its results should be regarded as preliminary.