Effect of Normal Pregnancy Followed by Lactation on Long-Term Maternal Health in a Mouse Model

Abstract

Although it has been widely accepted that pregnancies with complications are associated with increased maternal cardiovascular risk later in life, there is no consensus if noncomplicated pregnancy followed by lactation plays a protective role or is a risk factor. The objective of this study was to investigate the effects of normal pregnancy and lactation on long-term maternal health in a mouse model. CD-1 mice were allocated to breeding (primigravid [PG]) and nonbreeding (nulligravid [NG]) groups. The PG group proceeded through normal pregnancy and delivery. Using a telemetry system, blood pressure (BP) was analyzed in the PG group at 6 months postpartum and in age-matched NG mice. Serum analytes, gene expressions, and protein levels were determined using appropriate analysis methods. Primigravid mice had significantly lower systolic and diastolic BP and fasting glucose levels. Circulating oxytocin (OXT) levels were significantly higher in PG mice. Oxt gene expression was significantly higher in the heart and aorta and lower in visceral adipose tissue (VAT) from PG mice. The oxytocin receptor ( Oxtr) gene expression was significantly higher in the heart, aorta, and VAT from PG animals. The level of Oxtr DNA hypermethylation and the expression of mmu-miR-29a were significantly lower in the hearts of PG mice. In PG VAT, glucose transporter-4 expression was significantly higher. Our study demonstrates that a history of normal pregnancy followed by lactation was associated with lower maternal cardiovascular risk factors later in life in female mouse.

Keywords: cardiovascular; maternal; pregnancy.

Figure 1.

Experimental design of the study.

Figure 2.

(A) Systolic, (B) diastolic, and (C) mean blood pressures; (D) heart rate; and (E) pulse pressure in PG ( n = 6) and age-matched NG (n = 4) mice. Values are given as mean ± SEM. *Statistically significant differences (P < .05) between the PG and NG groups. NG indicates nulligravid; PG primigravid; SEM, standard error of the mean.

Figure 3.

The effect of KC) on carotid artery rings from NG (n = 9) and age-matched PG (n = 13) mice. The box extends from 25th percentile to the 75th percentile, with a line at the median (50th percentile). Whiskers show the highest and lowest values. KCl indicates potassium chloride; NG, nulligravid; PG primigravid.

Figure 4.

Concentration–response curves to relaxation agents (A) Ach (NG, n = 9; PG, n = 13), (B) SNP (NG, n = 9; PG, n = 12), and (C) ISO (NG, n = 9; PG, n = 12; P = .04) and to contractile agents (D) PE (NG, n = 9; PG, n = 13), (E) Tbx (U46619, NG, n = 9; PG, n = 13), and (F) 5-HT (NG, n = 9; PG, n = 10). Symbols represent mean ± SEM. Ach indicates acetylcholine; 5-HT, 5-hydroxytryptamine or serotonin; ISO, isoproterenol; NG, nulligravid; PE, phenylephrine; PG primigravid; SEM, standard error of the mean; SNP, sodium-nitroprusside; Tbx, thromboxane A₂ mimetic U46619.

Figure 5.

Plasma OXT concentrations in NG (n = 6) and age-matched PG (n = 5) mice at 10 months. The box extends from 25th percentile to the 75th percentile, with a line at the median (50th percentile). Whiskers show the highest and lowest values. NG indicates nulligravid; OXT, oxytocin; PG primigravid.

Figure 6.

Relative mRNA expression of the mmu-miR-29a in the heart from NG (n = 6) and age-matched PG (n = 5) mice at 10 months. The box extends from 25th percentile to the 75th percentile, with a line at the median (50th percentile). Whiskers show the highest and lowest values. mRNA indicates messenger RNA; NG, nulligravid; PG, primigravid.

Figure 7.

Relative mRNA expression of the Glut4 in the VAT from NG (n = 4) and age-matched PG (n = 5) mice at 10 months. The box extends from 25th percentile to the 75th percentile, with a line at the median (50th percentile). Whiskers show the highest and lowest values. Glut4 indicates glucose transporter-4; mRNA, messenger RNA; NG, nulligravid; PG, primigravid; VAT, visceral adipose tissue.

Figure 8.

Relative mRNA expression of the Lpl in the VAT from NG (n = 5) and age-matched PG (n = 6) mice at 10 months. The box extends from 25th percentile to the 75th percentile, with a line at the median (50th percentile). Whiskers show the highest and lowest values. Lpl indicates lipoprotein lipase; mRNA, messenger RNA; NG, nulligravid; PG, primigravid; VAT, visceral adipose tissue