Background: Exposure of pregnant women to stress and endocrine-disrupting chemicals (EDCs) during pregnancy can have a substantial impact on mother and infant health. We investigated the concentrations of EDCs, such as parabens (PBs) and triclosan (TCS), as well as stress hormones (cortisone and cortisol), across pregnancy trimesters and examined their associations with maternal average telomere length (TL). Methods: Hair samples from 49 postpartum women were analyzed using liquid chromatography–mass spectrometry (LC-MS) to quantify EDCs and stress hormone concentrations. Results: The mean methyl paraben concentrations in the hair of postpartum women were prevalent across all pregnancy trimesters, while butyl paraben was detected at the lowest levels. The mean concentration of PBs followed the order methyl > propyl > ethyl > benzyl > butyl paraben across pregnancy trimesters. We found that ethyl paraben and triclosan were each positively and significantly associated with cortisol levels in postpartum women’s hair. Consistent with this, the mean cortisone concentration gradually increased from the first to the third pregnancy trimester, whereas cortisol reached the highest mean concentration at the second trimester. A significant positive association between cortisol and cortisone levels was observed. Further analyses revealed that mothers’ average TL was positively associated with ethylparaben and triclosan levels and inversely associated with benzylparaben levels. Last but not least, we found that cortisol/cortisone levels were positively associated with postpartum women’s TL in a statistically significant manner. Conclusions: In the present study, prenatal exposure to stress hormones and EDCs appears to exert a statistically significant impact on maternal TL dynamics.

Cellular responses depend on the coordinated regulation of receptor activation, trafficking, and signaling across distinct membrane and intracellular compartments. Proteoglycans (PGs), traditionally regarded as structural components of the extracellular matrix and co-receptors, are now emerging as active organizers of receptor dynamics. This review examines the mechanisms through which PGs regulate receptor trafficking and spatial signaling in cancer. Recent studies addressing the roles of proteoglycans in receptor clustering, endocytic pathway selection, intracellular trafficking, recycling, lysosomal degradation, endosomal signaling, exosome biogenesis, and nuclear receptor transport were evaluated, with particular attention to the strength of direct evidence for trafficking. Particular attention was given to the complementary functions of proteoglycan core proteins, glycosaminoglycan chains, and extracellular matrix remodeling in shaping receptor behavior. Current evidence demonstrates that proteoglycans govern multiple stages of receptor biology by controlling ligand presentation, receptor accessibility, membrane organization, intracellular trafficking, and signaling persistence. Individual proteoglycans exert distinct effects on receptor fate, ranging from receptor downregulation and degradation to sustained endosomal signaling and nuclear receptor translocation. Cancer-associated alterations in proteoglycan expression, glycosaminoglycan sulfation, heparanase activity, ectodomain shedding, and glycocalyx organization remodel signaling networks, strengthen communication between tumor and stromal cells, and promote tumor progression, immune modulation, metastasis, and therapeutic resistance. Proteoglycans have emerged as fundamental regulators of receptor trafficking and signaling architecture. Through the integration of extracellular matrix organization with receptor dynamics, they shape the spatial and temporal properties of oncogenic signaling. This conceptual framework broadens our understanding of tumor biology and identifies proteoglycan-dependent regulation of receptor trafficking as a promising avenue for future therapeutic intervention.

Background/Objectives: Aging is increasingly recognized as a key determinant of changes in human tissue and cellular function. Women’s age, in particular, has been associated with reduced oocyte quality and negatively correlated with the expression of genes involved in endometrial decidualization and cellular function. The ability of endometrial cells to interact and allow the invasion of the growing embryo is defined as endometrial receptivity. Investigating age-related differences in human endometrial receptivity may expand our understanding of factors contributing to infertility. Methods: Stromal cells were isolated and cultured from endometrial pipelle biopsies (n = 28) obtained from female donors at the proliferative phase of the menstrual cycle. Protein and mRNA expression of the receptivity modulators OPN, CD44, and HOXA10 were analyzed by Western blot and real-time PCR, respectively. Results: Data presented a linear decrease in mRNA expression of OPN and HOXA10 (p = 0.0066, R² = 0.3018 and p = 0.0036, R² = 0.529, respectively) with women’s increasing age, and a similar trend was evident at the protein level (OPN, p < 0.05; HOXA10, p < 0.01). Further analysis of the data included separating the samples into three age groups: 25–35 years, 36–40 years, and 41–46 years. ANOVA revealed a significant decrease in OPN and HOXA10 mRNA expression (p = 0.03158 and p = 0.02578, respectively). CD44 expression did not differ with age. Conclusions: OPN and HOXA10 are negatively correlated with increasing maternal age. These findings suggest that age-related alterations in key endometrial receptivity modulators may contribute to impaired implantation and could represent potential targets for diagnostic or therapeutic strategies in human implantation failure.

Uterine stromal-derived tumors encompass a spectrum of rare neoplasms, ranging from benign endometrial stromal nodules to aggressive high-grade endometrial stromal sarcomas and undifferentiated uterine sarcomas. The classification of these tumors has advanced through molecular and immunohistochemical profiling, but the role of the extracellular matrix (ECM) in their biology is only beginning to be understood. The ECM provides both structural support and dynamic signaling cues, regulating tumor cell proliferation, invasion, angiogenesis, and immune evasion. Altered expression of collagens, proteoglycans, glycosaminoglycans, and matricellular proteins reshapes stromal architecture and contributes to disease progression. Moreover, ECM remodeling enzymes such as matrix metalloproteinases, together with cross-linking factors, create a stiff and pro-tumorigenic microenvironment that facilitates invasion and therapeutic resistance. Furthermore, these matrix alterations intersect with angiogenesis, mechanotransduction pathways, and immune modulation. Studies to date describe the role of ECM molecules in the function of the physiological uterine tissue and data for the uterine stroma-derived tumors is scarce. This review summarizes the existing knowledge in classification, prognosis and diagnosis, and summarizes the ECM-driven mechanisms in tumors described so far, aiming to identify new and prognostic biomarkers and novel therapeutic targets in uterine sarcomas.