Altered Maternal Circulating and Placental microRNA-369-5p and microRNA-671-3p Expression in Intrahepatic Cholestasis of Pregnancy: Comparison of ICSI and Spontaneous Conception.

To investigate microRNA-369-5p (miR-369-5p) and miR-671-3p expression in maternal peripheral blood leukocytes, plasma, and placental tissue in women with intrahepatic cholestasis of pregnancy (ICP) undergoing intracytoplasmic sperm injection (ICSI), compared with spontaneous conception. In this exploratory cohort study, microRNA-369-5p (miR-369-5p) and microRNA-671-3p (miR-671-3p) expression levels were analyzed using real-time quantitative PCR in maternal peripheral blood leukocytes, plasma, and placental tissue in four groups: (1) women with uncomplicated pregnancies conceived via intracytoplasmic sperm injection (non-ICP-ICSI, n = 7), (2) women with intrahepatic cholestasis of pregnancy conceived via intracytoplasmic sperm injection (ICP-ICSI, n = 7), (3) women with intrahepatic cholestasis of pregnancy who conceived spontaneously (ICP-SC, n = 7), and (4) women with uncomplicated pregnancies conceived spontaneously (non-ICP-SC, n = 7). Relative expression levels were calculated using the RQ method. Leukocyte miR-369-5p expression was significantly upregulated in ICP-ICSI and non-ICP-ICSI groups compared with ICP-SC and non-ICP-SC groups (p = 0.0001). Plasma miR-671-3p expression levels were significantly decreased in ICSI groups compared with spontaneous conception groups (p = 0.029). No significant differences were observed in placental expression levels of miR-369-5p and miR-671-3p among the four groups (p > 0.05). In subgroup analysis, leukocyte miR-369-5p and miR-671-3p expression levels were significantly higher in the ICP-ICSI group compared with the ICP-SC group (p < 0.05). Serum fasting bile acid levels showed a significant positive correlation with placental miR-369-5p expression (r = 0.467; p = 0.012) and a negative correlation with plasma miR-369-5p expression (r = -0.413; p = 0.029). Our findings show compartment-specific differences in miR-369-5p and miR-671-3p expression across leukocytes and plasma in this exploratory cohort. These preliminary observations do not establish causality and require validation in larger, independent cohorts.