Dataset Information

MyD88 Signaling in Trophoblasts is Necessary for Maternal High Fat Diet-Associated Developmental Programming of Obesity

ABSTRACT: Maternal obesity contributes to persistent programming of offspring obesity. A causal role for placental inflammatory mechanisms in developmental programming remains to be established. We examined the role of the toll-like receptor (TLR) pathway in mediating maternal obesity associated programming by trophoblast deletion of the TLR adapter protein, MyD88. Female MyD88fl/fl:Cyp19 Cre+ (MyD88-CKO) at 5 wks of age were provided control (17% fat calories, CON) or high-fat diets (HFD, 45% fat calories) for 12 wk and mated with MyD88fl/fl:Cyp19 Cre-(flox-control) males. Placenta were studied at dpc 17.5. In a subset, offspring were randomized to CON or HFD for 16 weeks. Placental weight and gene expression changes associated with HFD showed MyD88-dependence for pro-inflammatory and lipid metabolism related responses. Male MyD88 flox offspring from HFD-dams fed postnatal HFD (HH) showed an increase in body weight, liver steatosis and gene expression. These changes were absent in MyD88 CKO HH offspring, demonstrating a causal link between placental MyD88 mediated changes and long-term changes. Overall, these findings provide the first unequivocal evidence that placental changes due to maternal HFD are causally related to offspring obesity risk.

ORGANISM(S): Mus musculus

PROVIDER: GSE237410 | GEO | 2026/06/25

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Objective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.

Dataset Information

MyD88 Signaling in Trophoblasts is Necessary for Maternal High Fat Diet-Associated Developmental Programming of Obesity

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets