Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal. Mitophagy is the selective autophagy of mitochondria, eliminating dysfunctional mitochondria in cells by engulfment within double-membraned vesicles. Preeclampsia and low birth weight constitute prenatal complications during pregnancy and are leading causes of maternal and fetal mortality and morbidity. Both placental implantation and fetal growth require a large amount of energy, and a defect in the mitochondrial quality control mechanism may be responsible for the pathophysiology of these diseases. In this review, we compiled current studies investigating the role of BNIP3, DRAM1, and FUNDC1, mediators of receptor-mediated mitophagy, in the progression of preeclampsia and the role of mitophagy pathways in the pathophysiology of low birth weight. Recent studies have indicated that mitochondrial dysfunction and accumulation of reactive oxygen species are related to preeclampsia and low birth weight. However, due to the lack of studies in this field, the results are controversial. Therefore, mitophagy-related pathways associated with these pathologies still need to be elucidated. Mitophagy-related pathways are among the promising study targets that can reveal the pathophysiology behind preeclampsia and low birth weight.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres, on the other hand, are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity were decreased, and double strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

Objective: Preeclampsia (PE) is a hypertensive pregnancy disorder accompanied by proteinuria, maternal organ dysfunction, and abnormal placental angiogenesis. The expression differences of genes in decidua basalis and peripheral blood–derived mesenchymal stromal cells (MSCs) are effective in preeclampsia. It was aimed to investigate whether angiogenesis-related MSC transcripts previously implicated in placental vascular dysfunction exhibit differential expression in decidua-derived and peripheral blood–derived MSCs in preeclampsia. Methods: This study covers messenger RNA (mRNA) expression analysis of MSCs from decidua (hDMSCs) (n = 14) and peripheral blood (n = 14) (PBMSCs) obtained from a total of 28 samples containing placenta and peripheral blood samples of PE patients (n = 7, 37.6 ± 1.53 weeks) and a healthy group (n = 7, 38 ± 0.92 weeks). Vascular endothelial growth factor A (VEGFAA), metallopeptidase inhibitor 1 (TIMP1), ephrin A3 (EFNA3), and thrombospondin type-1 domain-containing protein 7A (THSD7A) were analyzed for gene expression levels using droplet digital polymerase chain reaction (ddPCR) due to its high sensitivity rate to detect small amounts of samples. Results: In hDMSC samples, expression levels of VEGFAA (fold change (FC) = 5.16), TIMP-1 (FC = 1.68), and EFNA3 (FC = 1.57) were downregulated, and THSD7A was upregulated (FC = 2.56) compared to the healthy group; however, they are not statistically significant. In PBMSC samples, VEGFAA (FC = 4.2), EFNA3 (FC = 1.39), and THSD7A (FC = 1.06) levels were upregulated, while TIMP-1 (FC = 2.4) was downregulated in preeclamptic samples. Vascular endothelial growth factor A was significantly (P < .05) increased (AUC = 0.95, P = .019) in PBMSC of preeclampsia patients. Conclusion: It was aimed to show the relation of MSC-related genes, angiogenesis, and preeclampsia. Vascular endothelial growth factor A elevation in PBMSCs suggests a potential systemic angiogenic response in preeclampsia, rather than concluding its primacy in fetoplacental development. Overall, the findings suggest that MSC-related angiogenic alterations may contribute to the pathophysiology of PE, supporting the need for larger studies to validate these preliminary observations. Cite this article as: Kumral Z, Gümüşoğlu Acar E, Sevgin K, et al. Transcriptome analysis on mesenchymal stromal cells derived from placenta and blood in preeclampsia. Cerrahpaşa Med J 2026, 50, 0015, doi: 10.5152/cjm.2026.26015.