miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Cell Biology

Background:

• Decidualization is critical for pregnancy establishment; its dysregulation is linked to early pregnancy loss.
• Previous work identified miR-3074-5p as promoting apoptosis and inhibiting human extravillous trophoblast (EVT) cell invasion.
• Elevated miR-3074-5p levels were observed in villus tissues of recurrent miscarriage (RM) patients.

Purpose of the Study:

• To investigate the role of miR-3074-5p in the decidualization of human endometrial stromal cells (ESCs).
• To explore the potential mechanism involving miR-3074-5p and CLN8 in early pregnancy failure.

Main Methods:

• Quantification of miR-3074-5p expression in decidual tissues from RM patients and controls.
• Overexpression of miR-3074-5p in an immortalized human ESC line (T-HESCs) to assess effects on proliferation and decidualization.
• Validation of CLN8 mRNA as a direct target of miR-3074-5p using luciferase assays.
• Analysis of CLN8 expression during in vitro decidualization and in RM patient tissues.

Main Results:

• Decidual miR-3074-5p expression was significantly higher in RM patients compared to controls.
• Overexpressing miR-3074-5p in T-HESCs suppressed cell proliferation and in vitro-induced decidualization.
• CLN8 mRNA was validated as a direct target of miR-3074-5p; CLN8 expression increased with decidualization.
• Downregulation of CLN8 inhibited T-HESC decidualization, and CLN8 expression was decreased in RM decidual tissues.

Conclusions:

• Increased miR-3074-5p in ESCs may impair decidualization via the miR-3074-5p/CLN8 pathway, contributing to early pregnancy failure.
• The miR-3074-5p/CLN8 axis represents a potential diagnostic and therapeutic target for recurrent miscarriage.