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Fig 1.

Effects of different diets on non-pregnant mice.

(A) Body weights of female mice fed the RC (dotted line, n = 5), LFD (dashed line, n = 5), or HFD (solid line, n = 5) for 4 weeks. (B) Blood glucose levels in mice fed the RC (circles, n = 4), LFD (squares, n = 5), or HFD (triangles, n = 5). Data are presented as mean ± SD. *p < 0.001, **p < 0.005 vs the RC and LFD groups using a one-way ANOVA test with Bonferroni correction.

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Fig 1 Expand

Fig 2.

Feeding regimens.

(A) Control regimen: RC at preconception and throughout pregnancy. (B) HFD-P regimen: RC at preconception and the HFD throughout pregnancy. (C) HFD-PreCP regimen: the HFD initiated 4 weeks preconception and throughout pregnancy.

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Fig 3.

Effects of diet regimens on pregnant mice.

(A) Body weight gain during pregnancy in mice fed the Control (dotted line, n = 16), HFD-P (dashed line, n = 10), or HFD-PreCP (solid line, n = 7) regimen. (B) Weights (g) of fetuses harvested at E16.5 from pregnant mice fed the Control (circles, n = 15), HFD-P (squares, n = 17), or HFD-PreCP (triangles, n = 17) regimen. C) Maternal glucose levels at 5 different gestational epochs: preconception, E6.5–E9.5; E10.5–12.5; E13.5–E15.5; and E16.5–E19.5 in dams fed the Control (circles), HFD-P (squares), or HFD-PreCP (triangles) regimens. Number of samples per group are shown in parentheses. Data are presented as mean ± SD. *p < 0.05, **p < 0.005, ***p < 0.0005, †p < 0.0001 using one-way ANOVA tests with Bonferroni corrections.

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Fig 4.

Placental gene expression at E9.5 and E11.5.

Alterations in gene expression (Hif1a, Angpt1, Pgf, Hmox1, Sod1, Gpx1, Ap2, and Nrf2) as measured using a custom qRT-PCR panel were found in placentas harvested from pregnant mice subjected to the Control (white bars) or HFD-P (black bars) regimen. Data are presented as mean ± SD fold change from the E8.5 RC group results. Number of samples per gestational age epoch per group are shown in parentheses.

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Fig 5.

Glycogen-rich GlyTs and uNK cells were identified by PAS staining in E14.5 placentas from mice fed the RC.

(A, B) uNK cells in the MG. (C, D) GlyTs surrounding the maternal blood canals in the decidua basalis region. (E, F) GlyTs in the junctional zone/decidua basalis region. (G, H) Pre-GlyT islets in the labyrinth. Junctional zone regions and cell islets in the labyrinth region are delineated by dashed green lines. Green triangles show GlyTs, SpTs, or uNK cells and the yellow asterisk denotes a giant cell (GC). n of 5 placentas from 3 pregnancies evaluated for each staining. Images on the left and right panels are shown at 200x and 400x magnification, respectively.

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Fig 6.

PAS-positive uNK (upper panels) and GlyTs (lower panels) in placentas.

Placentas were harvested from mice fed the: (A, D) Control; (B, E) HFD-P; or (C, F) HFD-PreCP regimen. Green triangles show GlyTs or uNK cells. n = 5 placentas from 3 pregnancies evaluated for each staining. Images are shown at 400x magnification.

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Fig 6 Expand

Fig 7.

HE (upper panels) or isolectin B4 (lower panels) staining of labyrinth regions.

Placentas were harvested from dams subjected to the: (A, D) Control; (B, E) HFD-P; or (C, F) HFD-PreCP regimen. Maternal red blood cells (non-nucleated) were small and shown clustered, while fetal red blood cells (nucleated) were isolated and denoted by green rings in the upper panels. Maternal sinusoid spaces are indicated by the green arrows, while fetal capillary spaces are indicated by the green triangles. n = 5 placentas from 3 pregnancies evaluated for each staining. Images are shown at 400x magnification.

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Fig 8.

Weights and glycogen content in placentas.

Placentas were harvested at (A, B) E14.5 and (C, D) E16.5 from pregnant mice subjected to the Control (circles), HFD-P (squares), or HFD-PreCP (triangles) regimens. Each placenta was then separated into the F-Placenta and MG. Weights (mg) of F-Placentas and MGs are shown at (A) E14.5 and (C) E16.5. Glycogen content is shown as mg/g placenta at (B) E14.5 and at (D) E16.5 with controls shown as circles; HFD-P as squares; and HFD-PreCP as triangles. Number of samples per group are shown in parentheses. Data are presented as mean ± SD. *p < 0.02; **p < 0.01; ***p < 0.005 using one-way ANOVA tests with Bonferroni correction.

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Fig 9.

A hypothesis for the pregnancy disorders caused by a HFD, obesity, and/or diabetes.

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