The role of dietary patterns in the polarization of angiogenic uterine Natural Killer cells during murine pregnancy

Uterine Natural Killer (uNK) cells, predominant leukocytes in mouse and human pregnant uteruses, play crucial roles in angiogenesis and pregnancy protection. In mice, DBA lectin-reactive uNK cells expressing Gal-N-Ac sugar exhibit angiogenic functions essential for pregnancy maintenance. This study compares the impact of different nutritional imbalances on mouse pregnancy and the activation of angiogenic DBA+ uNK cells to safeguard against pregnancy complications. High Fat (HF), High Carbohydrate (HC), High Protein (HP), and Food Restriction (FR) diets were administered from gestation day (GD) 1 to GD10 or until parturition. HF and HC diets led to reduced expression of DBA-identified N-acetyl-D-galactosamine, akin to LPS-induced inflammation, and decreased uNK perforin levels. Additionally, HF and HC diets resulted in elevated endometrial cleaved caspase-3 and decreased smooth muscle alpha-actin, causing blood vessel wall thinning without jeopardizing pregnancy term. FR impaired uNK differentiation, manifesting as an "all-or-none" phenomenon with 50% pregnancy failure. Our findings highlight the intricate relationship between nutritional imbalances and mouse pregnancy outcomes. Notably, high-fat diets elicited pronounced responses from DBA+ uNK cells, while high-protein diets had relatively weaker effects. This study underscores the importance of comprehending uNK cell dynamics in maintaining pregnancy homeostasis under diverse dietary conditions, paving the way for elucidating molecular mechanisms governing these interactions. By shedding light on these complex relationships, this research offers valuable insights for improving maternal and fetal health in the context of nutritional interventions during pregnancy.