SUN-705 Spontaneous Maternal Obesity Disrupts Fetal Immune Cell Function and Development in Nonhuman Primates

Abstract Disclosure: O. Varlamov: None. S. Sureshchandra: None. B.M. Doratt: None. H. True: None. U. Avilla: None. C.M. McGuire: None. C. Zaro: None. T. Hodge: None. L.D. Martin: None. L. Bader: None. D.L. Takahashi: None. I. Messaoudi: None. Maternal obesity is a growing global concern, as nearly 30% of women of reproductive age have obesity in the United States. Maternal obesity is linked to pregnancy complications, including preeclampsia, a higher likelihood of cesarean delivery, postpartum hemorrhage, and infections. Additionally, it can negatively impact fetal development, increasing the risk of metabolic syndrome, obesity, and preterm birth in offspring. While studies have begun to uncover the impact of maternal obesity on the fetal immune system, the underlying mechanisms remain poorly understood. Therefore, we initiated a study involving two groups of adult rhesus macaques—lean and obese—classified by body fat content. All animals were maintained on a regular low-fat monkey chow diet. Following metabolic testing, timed mating was performed. During pregnancy, obese dams exhibited higher body fat percentage, glucose intolerance, and insulin resistance compared to lean dams. Notably, obese dams showed signs of hypoglycemia in the third trimester. Additionally, fetuses from obese dams were significantly heavier than those from lean dams. Immunological analysis revealed that maternal obesity disrupts the development of myeloid and lymphoid immune cells in the fetus. Fetal spleen monocytes from obese dams showed increased production of IL-1 and IL-6. Single-cell analysis further revealed enhanced activation of B- and T-cells, as well as an expansion of monocytes and macrophages at the expense of hematopoietic stem cells. In conclusion, maternal obesity induces a proinflammatory state, prematurely activates fetal immune cells, and disrupts the differentiation of fetal hematopoietic stem cells. These immune alterations may contribute to the increased prevalence of infections and adverse outcomes observed in offspring of obese mothers. This study underscores the importance of maintaining a healthy weight during pregnancy across various dietary regimens. Presentation: Sunday, July 13, 2025