Androgens Upregulate Pathogen-Induced Placental Innate Immune Response

Area of Science:

• Reproductive immunology
• Neurodevelopmental disorders
• Infectious diseases

Background:

• Group B Streptococcus (GBS) causes chorioamnionitis, a placental infection linked to neurobehavioral impairments like autism spectrum disorders.
• These impairments are more prevalent in males, suggesting a sex-based biological influence.
• Previous studies noted a stronger placental inflammatory response in male-associated pregnancies, correlating with neurodevelopmental issues.

Purpose of the Study:

• To investigate the hypothesis that androgens upregulate the placental innate immune response in male fetuses during GBS-induced chorioamnionitis.
• To determine if blocking androgen receptors can mitigate the inflammatory response and its sex-specific effects.

Main Methods:

• A pre-clinical model using Lewis dams was employed.
• Dams were treated with an androgen receptor antagonist (flutamide) or vehicle from gestational days 18-21.
• On gestational day 19, dams were challenged with GBS or saline, with maternal and fetal tissues collected for analysis.

Main Results:

• Flutamide treatment alone did not affect placental parameters.
• In GBS-infected dams, flutamide administration reduced pro-inflammatory cytokine levels in placental tissue.
• Flutamide also decreased the infiltration of polymorphonuclear cells in the placenta of infected dams compared to controls.

Conclusions:

• Androgens play a role in upregulating the placental innate immune response during GBS infection.
• This androgen-mediated immune modulation may contribute to the higher incidence of male offspring affected by neurodevelopmental impairments following perinatal infections.