Interleukin-6 (IL-6) is an acknowledged inflammatory cytokine with a pleiotropic action, mediating innate and adaptive immunity and multiple physiological processes, including protective and regenerative ones. IL-8 is a pro-inflammatory CXC chemokine with a primary function in attracting and activating neutrophils, but also implicated in a variety of other cellular processes. These two ILs are abundantly expressed at the feto-maternal interface over the course of a pregnancy and have been shown to participate in numerous pregnancy-related events. In this review, we summarize the literature data regarding their role in healthy and pathological pregnancies. The general information related to IL-6 and IL-8 functions is followed by an overview of their overall expression in cycling endometrium and at the feto-maternal interface. Further, we provide an overview of their involvement in pregnancy establishment and parturition. Finally, the implication of IL-6 and IL-8 in pregnancy-associated pathological conditions, such as pregnancy loss, preeclampsia, gestational diabetes mellitus and infection/inflammation is discussed.

Polyphenols are a group of phytochemicals with extensive biological functions and health-promoting potential. These compounds are present in most foods of plant origin and their increased widespread availability through the intake of nutritional supplements, fortified foods, and beverages, has also led to increased exposure throughout gestation. In this narrative review, we focus on the role of polyphenols in both healthy and pathological pregnancy. General information related to their classification and function is followed by an overview of their known effects in early-pregnancy events, including the current insights into molecular mechanisms involved. Further, we provide an overview of their involvement in some of the most common pregnancy-associated pathological conditions, such as preeclampsia and gestational diabetes mellitus. Additionally, we also discuss the estimated possible risk of polyphenol consumption on pregnancy outcomes. The consumption of dietary polyphenols during pregnancy needs particular attention considering the possible effects of polyphenols on the mechanisms involved in maternal adaptation and fetal development. Further studies are strongly needed to unravel the in vivo effects of polyphenol metabolites during pregnancy, as well as their role on advanced maternal age, prenatal nutrition, and metabolic risk of the offspring.

Galectins are a family of conserved soluble proteins defined by an affinity for β-galactoside structures present on various glycoconjugates. Over the past few decades, galectins have been recognized as important factors for successful implantation and maintenance of pregnancy. An increasing number of studies have demonstrated their involvement in trophoblast cell function and placental development. In addition, several lines of evidence suggest their important roles in feto-maternal immune tolerance regulation and angiogenesis. Changed or dysregulated galectin expression is also described in pregnancy-related disorders. Although the data regarding galectins’ clinical relevance are still at an early stage, evidence suggests that some galectin family members are promising candidates for better understanding pregnancy-related pathologies, as well as predicting biomarkers. In this review, we aim to summarize current knowledge of galectins in early pregnancy as well as in pregnancy-related pathologies.

Olive-derived bioactive compound oleuropein was evaluated against damage induced by hydrogen peroxide in human trophoblast cells in vitro, by examining the changes in several markers implicated in oxidative stress interactions in the placenta. Trophoblast HTR-8/SVneo cells were preincubated with OLE at 10 and 100 µM and exposed to H₂O₂, as a model of oxidative stress. Protein and lipid peroxidation, as well as antioxidant enzymes’ activity, were determined spectrophotometrically, and DNA damage was evaluated by comet assay. iNOS protein expression was assessed by Western blot, while the mRNA expression of pro- and anti-apoptotic genes BAX and BCL2 and transcription factor NFE2L2, as well as cytokines IL-6 and TNF α were determined by qPCR. Oleuropein demonstrated cytoprotective effects against H₂O₂ in trophoblast cells by significantly improving the antioxidant status and preventing protein and lipid damage, as well as reducing the iNOS levels. OLE reduced the mRNA expression of IL-6 and TNF α, however, it did not influence the expression of NFE2L2 or the BAX/BCL2 ratio after H₂O₂ exposure. Oleuropein per se did not lead to any adverse effects in HTR-8/SVneo cells under the described conditions, confirming its safety in vitro. In conclusion, it significantly attenuated oxidative damage and restored antioxidant functioning, confirming its protective role in trophoblast.

Antiphospholipid syndrome (APS) is a complex thrombo-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL). Women with APS are at high risk of recurrent early pregnancy loss as well as late obstetrical complications—premature birth due to placental insufficiency or severe preeclampsia. Accumulating evidence implies that vascular thrombosis is not the only pathogenic mechanism in obstetric APS, and that the direct negative effect of aPL on the placental cells, trophoblast, plays a major role. In this review, we summarize the current findings regarding the potential mechanisms involved in aPL-induced trophoblast dysfunction. Introduction on the APS and aPL is followed by an overview of the effects of aPL on trophoblast—survival, cell function and aPL internalization. Finally, the implication of several non-coding RNAs in pathogenesis of obstetric APS is discussed, with special emphasis of their possible role in trophoblast dysfunction and the associated mechanisms.