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Chronic Estrogen Supplementation Prevents the Increase in Blood Pressure in Female Intrauterine Growth-Restricted Offspring at 12 Months of Age.

ABSTRACT: Low birth weight is associated with a greater prevalence of hypertension and an earlier age at menopause in women in later life. Yet, the association between birth weight and blood pressure (BP) in women as they age is not well defined. In a rodent model of low birth weight induced by placental insufficiency, intrauterine growth restriction programs a significant increase in BP by 12 months of age in female growth-restricted offspring that is associated with early reproductive senescence, increased testosterone, and a shift in the hormonal milieu. Thus, this study tested the hypothesis that increased BP in female growth-restricted offspring is abolished by chronic estradiol supplementation. Placebo or 17?-estradiol valerate mini pellets (1.5 mg for 60-day release) were administered at 12 months of age for 6 weeks. BP, measured in conscious catheterized rats, was significantly increased in placebo-treated growth-restricted relative to placebo-treated control. However, BP was not elevated in estradiol-treated growth-restricted relative to placebo-treated growth-restricted. Estradiol mediates its effects on BP via its receptors and the renin-angiotensin system. BP was decreased in growth-restricted offspring treated with a G-protein coupled receptor agonist, G1 (400 mg/kg for 2 weeks). Renal AT1aR (angiotensin type 1a receptor) and AT1bR (angiotensin type 1b receptor) and renal AR (androgen receptor) mRNA expression were elevated in vehicle-treated growth-restricted offspring, but not in G1-treated growth-restricted. Therefore, these data suggest that chronic estradiol supplementation prevents the increase in BP that develops in female growth-restricted offspring via actions that may involve its G-protein coupled receptor and the renin-angiotensin system.

SUBMITTER: Davis GK

PROVIDER: S-EPMC6458065 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Chronic Estrogen Supplementation Prevents the Increase in Blood Pressure in Female Intrauterine Growth-Restricted Offspring at 12 Months of Age.

Davis Gwendolyn K GK Newsome Ashley D AD Cole Alyssa B AB Ojeda Norma B NB Alexander Barbara T BT

Hypertension (Dallas, Tex. : 1979) 20190501 5

Low birth weight is associated with a greater prevalence of hypertension and an earlier age at menopause in women in later life. Yet, the association between birth weight and blood pressure (BP) in women as they age is not well defined. In a rodent model of low birth weight induced by placental insufficiency, intrauterine growth restriction programs a significant increase in BP by 12 months of age in female growth-restricted offspring that is associated with early reproductive senescence, increa ...[more]

PMID: 30929518

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Project description:OBJECTIVE:The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). METHODS:Using a 2×2 factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age. RESULTS:The results showed that the IUGR pigs had reduced body weight compared with the NBW pigs (p<0.05 from birth to d 120; p = 0.07 from d 120 to 200). Increased (p<0.05) free fatty acid (FFA) and triglyceride levels were observed in the IUGR pigs compared with the NBW pigs. Choline supplementation decreased (p<0.05) the levels of FFAs and triglycerides in the serum of the pigs. The activities of malate dehydrogenase and glucose 6-phosphate dehydrogenase were both increased (p<0.05) in the livers of the IUGR pigs. Choline supplementation decreased (p<0.05) malate dehydrogenase activity in the liver of the pigs. Gene expression of fatty acid synthase (FAS) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation decreased (p<0.05) FAS and acetyl-CoA carboxylase ? expression in the livers of the IUGR pigs. The expression of carnitine palmitoyl transferase 1A (CPT1A) was lower (p<0.05) in the IC group than in the other groups, and choline supplementation increased (p<0.05) the expression of CPT1A in the liver of the IUGR pigs and decreased (p<0.01) the expression of hormone-sensitive lipase in both types of pigs. The gene expression of phosphatidylethanolamine N-methyltransferase (PEMT) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation significantly reduced (p<0.05) PEMT expression in the liver of the IUGR pigs. CONCLUSION:In conclusion, the lipid metabolism was abnormal in IUGR pigs, but the IUGR pigs consuming twice the normal level of choline had improved circulating lipid parameters, which could be related to the decreased activity of nicotinamide adenine dinucleotide phosphate-generating enzymes or the altered expressions of lipid metabolism-related genes.

Project description:Epidemiological studies report an inverse association between birth weight and risk for kidney disease that may differ between males and females, but studies investigating this association are limited. This study tested the hypothesis that male intrauterine growth-restricted offspring in a model of low birth weight induced by placental insufficiency in the rat exhibit enhanced renal injury in response to a persistent secondary renal insult while female growth-restricted offspring are protected. For this study, control offspring from sham-operated dams and growth-restricted offspring from reduced uterine perfusion dams underwent uninephrectomy or a sham procedure at 18 months of age. One month later, urinary markers of renal injury, renal function, and histological damage were measured. Results were analyzed using 2-way ANOVA. Male and female offspring were assessed separately. Proteinuria and urinary neutrophil gelatinase-associated lipocalin were significantly elevated in male growth-restricted offspring exposed to uninephrectomy when compared to male uninephrectomized control. Urinary kidney injury marker-1 was elevated in male uninephrectomized growth-restricted offspring relative to male sham growth-restricted but not to male uninephrectomized controls. Likewise, urinary neutrophil gelatinase-associated lipocalin was elevated in female uninephrectomized growth-restricted offspring but only when compared to female sham growth-restricted offspring. Markers of renal function including glomerular filtration rate and serum creatinine were impaired after uninephrectomy in female offspring regardless of birth weight. Histological parameters did not differ between control and growth-restricted offspring. Collectively, these studies suggest that both male and female growth-restricted offspring demonstrate susceptibility to renal injury following uninephrectomy; however, only male growth-restricted offspring exhibited an increase in renal markers of injury in response to uninephrectomy relative to same-sex control counterparts. These findings further suggest that urinary excretion of protein, kidney injury marker-1, and neutrophil gelatinase-associated lipocalin may be early markers of kidney injury in growth-restricted offspring exposed to a secondary renal insult such as reduction in renal mass.

Dataset Information

Chronic Estrogen Supplementation Prevents the Increase in Blood Pressure in Female Intrauterine Growth-Restricted Offspring at 12 Months of Age.

Publications

Chronic Estrogen Supplementation Prevents the Increase in Blood Pressure in Female Intrauterine Growth-Restricted Offspring at 12 Months of Age.

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