Endometrial stromal cells play an important role in reproductive success, especially in implantation and placentation. Although Mesenchymal stem cells (MSCs) have been studied to assess decidualization disorders in preeclampsia (PE), their role during trophoblast invasion remains unclear. This study aims to determine: (i) whether MSCs isolated from menstrual fluid (MenSCs) from nulliparous, multiparous, and women with a previous history of preeclampsia exhibited different patterns of proliferation and migration and (ii) whether reproductive history (i.e., prior pregnancy or prior history of PE) was able to produce changes in MenSCs, thus altering trophoblast invasion capacity. MenSCs were collected from nulliparous and multiparous women without a history of PE and from non-pregnant women with a history of PE. Proliferation and migration assays were performed on MenSCs with sulforhodamine B and transwell assays, respectively. Trophoblast invasion was analyzed by culturing HTR-8/SVneo trophospheres on a matrigel overlying MenSCs for 72 h at 5% O2, simulating a 3D implantation model. A previous history of pregnancy or PE did not impact the proliferative capacity or migratory behavior of MenSCs. Following exposure to physiological endometrial conditions, MenSCs demonstrated upregulated expression of IGFBP-1 and LIF mRNA, decidualization and window of implantation markers, respectively. The mRNA expression of VIM, NANOG, and SOX2 was upregulated upon trophosphere formation. Relative to co-culture with multiparous MenSCs, co-culture with PE-MenSCs was associated with reduced trophoblast invasion. The findings of this study suggest a potential role for communication between maternal MenSCs and invading trophoblast cells during the implantation process that could be implicated in the etiology of PE.

Preeclampsia, a disorder with a heterogeneous physiopathology, can be attributed to maternal, fetal, and/or placental factors. Long non-coding RNAs (lncRNAs) refer to a class of non-coding RNAs, the essential regulators of biological processes; their differential expression has been associated with the pathogenesis of multiple diseases. The study aimed to identify lncRNAs, expressed in the placentas and plasma of patients who presented with preeclampsia, as potential putative biomarkers of the disease. In silico analysis was performed to determine lncRNAs differentially expressed in the placentas of patients with preeclampsia, using a previously published RNA-Seq dataset. Seven placentas and maternal plasma samples collected at delivery from preterm preeclamptic patients (≤37 gestational weeks of gestation), and controls were used to validate the expression of lncRNAs by qRT-PCR. Six lncRNAs were validated and differentially expressed (p < 0.05) in the preeclampsia and control placentas: UCA1 and HCG4 were found upregulated, and LOC101927355, LINC00551, PART1, and NRAD1 downregulated. Two of these lncRNAs, HCG4 and LOC101927355, were also detected in maternal plasma, the latter showing a significant decrease (p = 0.03) in preeclamptic patients compared to the control group. In silico analyses showed the cytoplasmic location of LOC101927355, which suggests a role in post-transcriptional gene regulation. The detection of LOC101927355 in the placenta and plasma opens new possibilities for understanding the pathogenesis of preeclampsia and for its potential use as a biomarker.

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