Oxidative injuries induced by maternal low-protein diet in female brainstem

Abstract

Many studies have shown that a maternal low-protein diet increases the susceptibility of offspring to cardiovascular disease in later-life. Moreover, a lower incidence of cardiovascular disease in females than in males is understood to be largely due to the protective effect of high levels of estrogens throughout a woman's reproductive life. However, to our knowledge, the role of estradiol in moderating the later-life susceptibility of offspring of nutrient-deprived mothers to cardiovascular disease is not fully understood. The present study is aimed at investigating whether oxidative stress in the brainstem caused by a maternal low-protein diet administered during a critical period of fetal/neonatal brain development (i.e during gestation and lactation) is affected by estradiol levels. Female Wistar rat offspring were divided into four groups according to their mothers' diets and to the serum estradiol levels of the offspring at the time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet. Undernutrition in the context of low serum estradiol compared to undernutrition in a higher estradiol context resulted in increased levels of oxidative stress biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses. Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers had received a low-protein diet. In the 122-day-old group, we observed a decrease in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a positive oxy-score when compared to control. We conclude from these results that following a protein deficiency in the maternal diet during early development of the offspring, estrogens present at high levels at reproductive age may confer resistance to the oxidative damage in the brainstem that is very apparent in pre-pubertal rats.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

“…Low-protein regimens at conception or during pregnancy bring additional evidence on the noxious epigenetics effects of maternal nutrition deficiency on the offspring health: in animal models, a protein-restricted maternal diet has been associated with impaired immune response ( 42 ), increased sensitivity to oxidative stress ( 43 ), metabolic abnormalities, and glucose dyshomeostasis ( 44 ).…”

Serotonin transporter inhibition during neonatal period induces sex‐dependent effects on mitochondrial bioenergetics in the rat brainstem

“…In regard to oxidative balance, our data demonstrated that females are more protected from oxidative damage than male animals in brainstem, wherein the lower production of ROS gathered with a high CAT activity and elevated thiol content culminated in a compelling lower lipid peroxidation. The oxidative stress protection in female gender has been widely described in oestrogen-related neuroprotection studies due to its capacity to upregulate the expression of several antioxidant enzymes (Irwin et al, 2008;Moor et al, 2004;Yao et al, 2012), similarly to in the brainstem or brainstem nuclei (Lee, Ryu, & Lee, 2013;Pierce et al, 2009;Shih, 2009;de Sousa et al, 2017;Subramanian et al, 2011;Wang & He, 2002;Wang et al, 2008;Wu, Chen, & Shih, 2012).…”

Maternal protein malnutrition induced‐hypertension: New evidence about the autonomic and respiratory dysfunctions and epigenetic mechanisms

“…The researchers suggest that female hormones could be relevant in the prevention of hypertension in pre‐menopausal females . In addition, hyperactivity of the rennin‐angiotensin system and augmented oxidative stress, relevant features in hypertensive condition, are not changed in female offspring exposed to maternal protein malnutrition . Please note that it is not the focus of this review to perform a comparison between genders in maternal malnutrition induced‐hypertension models.…”

“…41 In addition, hyperactivity of the rennin-angiotensin system and augmented oxidative stress, relevant features in hypertensive condition, are not changed in female offspring exposed to maternal protein malnutrition. 44,45 Please note that it is not the focus of this review to perform a comparison between genders in maternal malnutrition induced-hypertension models. For better understanding of the evidence for sex differences in developmental programming of hypertension see Ojeda and colleagues (2008) 46 and Davis and colleagues (2017).…”