Fetal Sex Modulates Hofbauer Cells' Response to Diabetes in Human Placenta

Area of Science:

• Immunology
• Reproductive Biology
• Perinatal Medicine

Background:

• Hofbauer cells (HBCs) are fetal macrophages crucial for immune tolerance at the feto-maternal interface.
• These cells predominantly exhibit an M2 phenotype, marked by CD206 expression.

Purpose of the Study:

• To investigate the impact of maternal diabetes (type 1 and gestational) and fetal sex on Hofbauer cell characteristics.
• To assess CD206 expression, morphology, and apoptotic body accumulation in placental villi.

Main Methods:

• Immunohistochemistry and morphometric analysis were employed to quantify HBCs and CD206 intensity.
• Apoptotic body accumulation was evaluated in placental villi from pregnancies with type 1 diabetes mellitus (T1DM), gestational diabetes mellitus (GDM), and normoglycemic controls.
• Comparisons were made based on maternal diagnosis and fetal sex.

Main Results:

• Maternal diabetes and fetal sex significantly affected CD206 intensity and apoptotic body accumulation, with a notable interaction between diagnosis and sex.
• CD206 intensity decreased progressively from controls to GDM and T1DM, with a more pronounced reduction in females. Reduced CD206 correlated with altered HBC morphology and increased IL-1β.
• Apoptotic body accumulation increased from controls to GDM and T1DM, with higher counts observed in male fetuses.

Conclusions:

• Maternal diabetes is linked to reduced CD206 expression, altered HBC morphology, and increased apoptotic bodies in the placental villi.
• These findings suggest that maternal diabetes compromises the tolerogenic capacity of the placental immune environment.
• Female fetuses may exhibit greater Hofbauer cell plasticity, potentially contributing to a more tolerogenic placental environment.