Introduction
It is believed that an inadequate intrauterine environment can affect fetal growth and development, leading to aberrant, permanent programming of the metabolic and endocrine function (Deodati et al., 2020). Fetal programming is an adaptive response of the organism to the environment. This ability is called “developmental plasticity” which allows the development of a spectrum of phenotypes from a single genotype (Lucas et al., 1991; Gluckman and Hanson, 2004). It allows the organism to respond to the surrounding environment, especially during early development, when cells are differentiating and tissues are developing. This plasticity is based on modifications of cellular pathways leading altered gene expression and the induction of specific phenotypes, but without modification of DNA sequence (Hanson and Gluckman, 2008; Barouki et al., 2012). Thus, early metabolic events during the pre-natal period may be associated with susceptibility to chronic diseases later in the adult life (Gluckman et al., 2005).
Maternal obesity and gestational diabetes, for example, have been shown to provoke long-term detrimental changes in the pathways that regulate energy balance in offspring. Notably, the increase in obesity and diabetes, as well as metabolic syndrome and fatty liver disease coincided with the increase in fructose in recent years (Muriel et al., 2021). In recent decades the daily intake of free fructose or as high fructose corn syrup has increased markedly. These forms of fructose are used in the food industry for their sweetness, palatability, solubility, low cost and high production efficiency compared to sugar (Cioffi et al., 2017). Ancestral diets showed that the average fructose intake was 2 kg per year, while the current global average consumption is 25 kg per year (Kmietowicz, 2012). More recently, fructose consumption has been estimated at 117 g/day in women and 162 g/day in men in world, and that, to consume this excess fructose via industrialized foods it is necessary to consume a 350 mL can of soda a day, while when eating fruits one would have to consume 1.3 kg of banana, 4.3 kg of strawberry, 800 g of apple and 900 mL of orange juice a day. In the latest data from Vigitel Brazil for 2018, it was observed that, in the set of 27 cities evaluated, the frequency of consumption of five or more groups of ultra-processed foods (rich in fructose and glucose) was 18.2%, being higher among men (21.8%) than among women (15.1%) (Ministry of Health, 2019).
Research with animals, showed that after 8 weeks of high fructose consumption, rats developed features of the metolinic syndrome along with mitochondrial structural changes (Mamikutty et al., 2014). In this context, Magenis et al. (2020) evaluated the effects of fructose treatment during pregnancy and lactation in mice, and observed an increased in DNA damage, hyperglycemia and hyperlipidemia in females that received doses of 10 and 20%/L fructose/day. Corroborating with this, Magenis et al. (2022) observed that the offspring (males and females) of these females, in both dosage groups, demonstrated genotoxicity (assessed by the comet assay) and oxidative stress (assessed by nitrite concentration, sulfhydryl content, and superoxide dismutase activity) in peripheral tissues. In addition, they showed nutritional and metabolic changes due to increased food consumption, hyperglycemia, hyperlipidemia and metabolic syndrome. Therefore, it was suggested that high fructose consumption by pregnant females was harmful to their offspring. However, it is believed that early dietary changes, both in mothers and children, significantly contribute to alleviate or assist in the treatment of these pathologies (Frias and Grove, 2012).
In this context, seeking alternatives to protect the damage caused to fetal programming are necessary in order to search new treatments. Although, the practice of physical exercise increased among Brazilians according to Vigitel data (2019), the proportion of women performing some type of physical activity dropped from 15.7% in 2013 to 14.2% in 2018 (Ministry of Health, 2019). More worrying is the sedentary lifestyle during pregnancy, since only 4.7% of pregnant Brazilian women are active throughout this period and 12.9% of women reported some physical activity during pregnancy as recommended by the American College of Obstetricians and Gynecologists (ACOG) (Domingues and Barros, 2007). In addition, it is observed that 50% of women at reproductive age and 20–25% of pregnant women in Europe are overweight or obese at the first antenatal visit (Stevens et al., 2012).
Guidance for physical exercise during pregnancy has been encouraged and recommended by the ACOG since the 1990s, but only in 2002 was this practice recognized as safe and indicated for healthy pregnant women. Through a systematic review and meta-analysis, Davenport et al. (2018) observed that pregnant women who exercised have a 39% reduced chance of having a baby weighing more than four kilos compared to those who did not exercise. It was also shown that the practice of exercise during pregnancy is not related to intrauterine growth restriction, premature birth and low birth weight, thus being safe and beneficial for the fetus. The ACOG advises pregnant women, even if they are sedentary, to perform at least 30 minutes of physical exercise on as many days of the week as possible (ACOG, 2002). In São Paulo, it was observed in the pregnant population that only 13% developed some type of physical activity, and only half of them performed exercises with frequency guided by the ACOG (Surita et al., 2014).
So far research in animals observed that maternal exercise before and during pregnancy does not seem to affect the body composition of offspring in healthy mice (Kelly et al., 2015). In an animal model of maternal obesity induced by a high-fat diet and treated with treadmill exercise, it was observed that the intervention had beneficial effects in relation to insulin resistance, excess placental lipid deposition and its hypoxia in offspring (Fernandez-Twinn et al. al., 2017). Moreover, Brito et al. (2016) observed that maternal physical exercise decreases DNA damage and oxidative stress caused by doxorubicin in offspring cardiomyocytes. In addition, Netto et al. (2018) observed that the practice of swimming in pregnant females with streptozotocin-induced diabetes by contributed to the reduction of DNA damage and lipid peroxidation in the mother and in her offspring.
To understand the effect of lifestyle and levels of DNA damage on pregnancy, further studies are needed, with sample collection from preconception, pregnancy and its offspring. Thus, the objective of the study is to evaluate whether the practice of voluntary physical exercise associated with chronic consumption of fructose from the pre-pregnancy period and/or until the pregnancy period causes biochemical and genotoxic alterations in breeding females, as well as genotoxic and biochemical alterations in their offspring.