Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88

Area of Science:

• Reproductive biology
• Immunology
• Molecular signaling

Background:

• Intrauterine infection is a known risk factor for preterm birth and other adverse pregnancy outcomes.
• Placental corticotrophin-releasing hormone (CRH) plays a crucial role in regulating pregnancy duration and parturition.
• The role of Toll-like receptor (TLR) signaling in mediating placental responses to infection is not fully understood.

Purpose of the Study:

• To investigate the hypothesis that intrauterine infection stimulates placental CRH expression through TLR signaling.
• To elucidate the specific TLR signaling pathways involved in mediating this response.

Main Methods:

• JEG3 placental cells were stimulated with lipopolysaccharide (LPS), chlamydial heat shock protein 60, and IL-1.
• CRH expression was quantified using reverse transcription polymerase chain reaction (RT-PCR).
• Signaling pathways were analyzed using transient transfection with dominant-negative vectors for MyD88 and TRIF, followed by luciferase assays.

Main Results:

• LPS, chlamydial heat shock protein 60, and IL-1 all induced CRH expression in JEG3 cells.
• LPS-induced CRH expression was mediated by MyD88, as dominant-negative MyD88 blocked the effect, while dominant-negative TRIF did not.
• The cyclic adenosine monophosphate (cAMP) response element was not implicated in LPS-induced CRH expression.

Conclusions:

• Toll-like receptor 4 signaling is implicated in the induction of placental CRH expression.
• The MyD88-dependent pathway is the primary mechanism through which TLR4 signaling mediates CRH expression in response to infection-associated stimuli.