Determining Sex-Specific Gene Expression Differences in Human Chorion Trophoblast Cells

Area of Science:

• Reproductive biology
• Immunology
• Genetics

Background:

• Male and female neonates exhibit distinct premature birth outcomes and placental inflammation.
• Sex-based differences in chorionic trophoblast cells (CTCs) inflammation are not well understood.
• Investigating sex-based variations in CTCs is crucial for understanding preterm birth.

Purpose of the Study:

• To investigate sex-based differences in gene and inflammatory marker expression in human chorionic trophoblast cells (CTCs).
• To examine CTC responses under both control and infectious inflammatory conditions simulating preterm birth.
• To determine if sexual dimorphism observed in placental inflammation extends to the chorion layer.

Main Methods:

• Cultured CTCs from patient-derived fetal membrane samples (3 male/3 female).
• Exposed CTCs to Lipopolysaccharide (LPS) or control conditions for 6, 12, or 24 hours.
• Analyzed gene expression via RNA-seq and measured cytokines, progesterone, and soluble HLA-G using multiplex assays and ELISA.

Main Results:

• CTCs displayed sex, time, and stimulant-dependent differential gene expression profiles.
• Male CTCs produced significantly lower IL-6 in control conditions compared to female CTCs.
• Male CTCs produced significantly lower progesterone than female CTCs; no sex-dependent cytokine response to LPS was observed.

Conclusions:

• The chorion layer may act as a protective barrier, being refractory to inflammatory insults.
• Theories of sexual dimorphism in placental inflammation may not apply to chorionic trophoblast cells.
• Further research is needed to explore potential weaknesses in the chorion barrier and sex-dependent fetal membrane responses.