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Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status
Pilar Rodríguez-Rodríguez1, Angel Luis López de Pablo1, Luis Condezo-Hoyos1
1Departmento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Insights
Maternal undernutrition during pregnancy programs male offspring for hypertension, while females are protected. Perinatal oxidative status differences, not just hormones, may explain this sex-based difference in hypertension development.
Area of Science:
- Reproductive biology
- Developmental programming
- Cardiovascular physiology
Background:
- Intrauterine growth retardation (IUGR) is linked to hypertension, a phenomenon known as fetal programming.
- Females are generally less susceptible to this programming, often attributed to estrogen.
- Perinatal oxidative stress may also play a role in sex-specific hypertension development.
Purpose of the Study:
- To investigate the role of perinatal oxidative status in sex-specific hypertension programming due to maternal undernutrition (MUN).
- To compare oxidative biomarkers and blood pressure in male and female offspring from control and MUN dams.
Main Methods:
- Studied male and female rat offspring at prepuberal (21-day-old) and adult (6-month-old) stages.
- Assessed blood pressure and plasma oxidative status biomarkers (carbonyls, thiols, GSH, antioxidant capacity, SOSA, catalase).
- Calculated a global oxidative score (oxy-score) and measured estradiol and melatonin.
Main Results:
- Prepuberal male offspring from MUN dams showed altered oxidative status (lower antioxidants, lower oxy-score) but were normotensive.
- Adult male offspring from MUN dams developed hypertension with increased oxidative stress.
- Adult female offspring from MUN dams remained normotensive with no significant differences in oxidative biomarkers compared to controls.
Conclusions:
- Perinatal oxidative status differences contribute to sex-specific hypertension programming.
- Maternal undernutrition programs males for hypertension, while females exhibit protection.
- Enhanced global antioxidant status in female offspring may protect against hypertension development.
Abstract:
Intrauterine growth retardation predisposes to hypertension development, known as fetal programming. Females are less susceptible, which has been mainly attributed to estrogen influence. We hypothesize that perinatal differences in oxidative status might also contribute. We studied 21-day-old (prepuberal) and 6-month-old male and female offspring from rats fed ad libitum during gestation (Control) or with 50% of Control daily intake from day 10 to delivery (maternal undernutrition, MUN). We assessed in vivo blood pressure and the following plasma biomarkers of oxidative status: protein carbonyls, thiols, reduced glutathione (GSH), total antioxidant capacity, superoxide anion scavenging activity (SOSA) and catalase activities; we calculated a global score (oxy-score) from them. Estradiol and melatonin concentration was measured in young rats. Prepuberal MUN males were normotensive but already exhibited increased carbonyls and lower thiols, GSH, SOSA and melatonin; oxy-score was significantly lower compared to Control males. Prepuberal MUN females only exhibited reduced SOSA compared to Control females. Adult rats from all experimental groups showed a significant increase in carbonyls and a decrease in antioxidants compared to prepuberal rats; oxy-score was negative in adult rats suggesting the development of a prooxidative status as rat age. Adult MUN males were hypertensive and exhibited the highest increase in carbonyls despite similar or even higher antioxidant levels compared to Controls. Adult MUN females remained normotensive and did not exhibit differences in any of the biomarkers compared to Controls. The better global antioxidant status developed by MUN females during perinatal life could contribute to their protection against hypertension programming.
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