Maternal plasma extracellular vesicles tsRNA as potential biomarkers for assessing preterm labor risk

Table 3 Gestational dynamics of tsRNA1 and tsRNA3: hypotheses and mechanisms

Gestational Stage	tsRNA	Expression Trend	Proposed Mechanism
First Trimester	tsRNA1	Significantly elevated	Regulation of epigenetic reprogramming during trophoblast differentiation (DNMT/TET balance) [57,58,59]
First Trimester	tsRNA3	Significantly elevated	Early placental development and immune adaptation at the maternal-fetal interface [60, 61]
Second Trimester	tsRNA1	Plateau	Reduced demand for epigenetic remodeling after completion of placental invasion [62, 63]
Second Trimester	tsRNA3	Further elevation	Immune modulation triggered by oxidative stress (e.g., mitochondrial load) or pathogen-associated molecules [64, 65]
Third Trimester	tsRNA1	Late-term elevation	Placental aging or endoplasmic reticulum stress-induced release [66, 67]
Third Trimester	tsRNA3	Pre-labor elevation	Activation of inflammasome pathways (e.g., NLRP3/IL-1β) to initiate labor-associated inflammation [67, 68]

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