**8. Programming**

*Cardiorespiratory Fitness*

**7. Animal studies**

adult-onset hypertension [44].

quent risk of atherogenesis in the offspring [42].

units are formed prenatally in the human fetus [43].

insulin resistance in childhood in humans [46].

increased sensitivity to postnatal stress [50].

activity, and neuroendocrine control [51–54].

are formed prenatally in the human fetus.

As a consequences, an infant usually has about 5–6 billion fat cells during the third trimester when a mother is pregnant. This number increases during early childhood and puberty, resulting in a healthy adult body possessing 25–30 billion fat cells [40]. Meanwhile, excessive energy supply to the fetus or infant will increase the potential of becoming obese. Babies who depend on milk factory have the highest amount of energy, leading to an increase in body weight than children who were breastfed; it can affect the increase in obesity and its risks later in life [41]. This complicate the long-term effects due to Prenatal and postnatal nutrition during early infancy. In one study, carotid intima-media thickness at 9 years of age in 216 children of European ancestry whose mothers had energy intake in the lowest quartile during early or late pregnancy was higher than that of children whose mothers had intake in the highest quartile, implying that maternal nutrition during pregnancy can affect the subse-

Thus, obesity comes from an increase in the numbers of fat cells, or adipocytes, and is hence due to a shift in the activity of certain genes during development. Because to maternal malnutrition during pregnancy, the offspring later suffering from obesity in the middle of the abdomen and lack of muscle mass, change the sensitivity of insulin, change in hepatic metabolism, decreased number of nephrons, high blood pressure, with a change in appetite regulation, activity level, and control of nerve endocrine glands [42]. There are critical periods in the differentiation and maturation of the tissues and cells involved in organogenesis throughout gestation and early postnatal life. The examples of the kidney, heart, and pancreas were obvious since their functional

Embryos of pregnant rats fed with a low-protein diet during the preimplantation period (0–4.25 days) show altered development in multiple organ systems; the offspring had reduced birth weights, relatively increased postnatal growth, and

Obviously, the preconception period is particularly sensitive, so that even the required nutrient deficiencies (B12 or folate or methionine) can have an effect on metabolism and blood pressure later in sheep [45]. It has recently been reported that the imbalance in B12 folic acid status and pain during pregnancy contributes to

Glucocorticoid management to pregnant rats at specific times during pregnancy to cause high blood pressure [47], insulin resistance in offspring later in life [48], changes in gene expression in the developing brain of offspring, and increased sensitivity to stress after the birth have been reported. The administration of glucocorticoids to the pregnant rat at specific points during gestation has been reported to cause hypertension [47], insulin resistance in the offspring in later life [49], alterations in gene expression in the developing brain of the offspring, and

In mice, it may lack nutrition during pregnancy to breed showing later the following: visceral obesity, reduced lean body mass, changes in insulin sensitivity, different hepatic metabolism, decreased numbers of nephrons, high blood pressure, and altered endothelial function, together with altered appetite regulation, level of

There are critical periods in the differentiation and maturation of the tissues and cells involved in organogenesis throughout gestation and early postnatal life. The examples are seen in the kidney, heart, and pancreas, since their functional units

**44**

Developmentally induced epigenetic modifications of DNA are generally stable during the mitotic cell divisions that continue throughout a lifetime. So, developmental plasticity of fetus through cell-cell interaction can be understood as a set of programs. "Programming" is the term used to describe lifelong changes in function that follow a particular event in an earlier period of the life span. Evolutionary plasticity requires a constant modification of genetic expression that appears to be mediated, at least in part, by genetic processes such as epigenetic mechanisms as cells use to control gene expression by virtue of DNA methylation. The role of DNA methylation in gene expression can be found in Phillips [57], and by a histone modification which is a histone protein includes methylation that can impact gene expression [58].

Several studies show that skeletal muscle can be programmed, where early exposure to environmental stimuli leads to a constant change in the skeletal muscle phenotype in later life. This has been demonstrated in mammalian models where reduced nutrient availability during pregnancy weakens muscle fibers, muscle and skeletal formation (white/red fiber ratios), and birth size [59]. Epidemiological studies in human aging groups also suggest that low birth weight and gestational malnutrition are closely related to reduced muscle size, skeletal strength, and aging [59, 60].

This refers to changes in gene expression due to nongenetic structural alterations of DNA and/or histones [58]. So, remember that cell-cell interaction can be transferable in the fetus so memory of active person eventually will be available later in life for the offspring babies [58]. Thus, developmental plasticity requires both the genome and the genetic variability of the environment interactively by the mature phenotype and determines the sensitivity and subsequent environmental factors and the subsequent risk of the disease affects [61]. The effects of maternal nutrition and behavior clearly target the promoter regions of specific genes rather than being associated with global changes in DNA methylation. DNA modulates the rate of transcription to messenger RNA. The phenotypic effects of epigenetic modifications during development may not manifest until later in life [62].
