What is fetal programming?: a lifetime health is under the control of in utero health

Abstract

The "Barker hypothesis" postulates that a number of organ structures and associated functions undergo programming during embryonic and fetal life, which determines the set point of physiological and metabolic responses that carry into adulthood. Hence, any stimulus or insult at a critical period of embryonic and fetal development can result in developmental adaptations that produce permanent structural, physiological and metabolic changes, thereby predisposing an individual to cardiovascular, metabolic and endocrine disease in adult life. This article will provide evidence linking these diseases to fetal undernutrition and an overview of previous studies in this area as well as current advances in understanding the mechanism and the role of the placenta in fetal programming.

Keywords: Chronic disease; Fetal development; Fetal nutrition disorders.

Fig. 1

Fetal adaptations to undernutrition: a framework [7]. IGF, insulin-like growth factor.

Fig. 2

The original diagrammatic representation of the thrifty phenotype hypothesis [25].

Fig. 3

An updated diagram of the thrifty phenotype hypothesis incorporating recent findings and concepts. Also included are new speculative features; maternal hyperglycemia as predisposing factor and key roles of the vascular, hypothalamic-pituitary-adrenal axis and sympathetic systems [25].

Fig. 4

Fetal programming framework, indicating the possible role of the endocrine, nutrient, and cardiovascular milieu in utero [27].

Fig. 5

Placental adaptive responses and fetal programming [55]. 11β-HSD, 11β-hydroxysteroid dehydrogenase; GLUT1, glucose transporter 1.

Fig. 6

The secernin-1 (SCRN1) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) protein expression in the whole brain of 3-week-old offspring by using Western blot analysis [58]. C, control; FR, food-restricted. All values are given as mean±standard deviation. ^a) P<0.05; ^b) P<0.01 (Wilcoxon rank-sum test).

Fig. 7

Comparison of liver protein expression in the offspring according to maternal diet [59]. The ratio of betaine-homocysteine methyltransferase 1 (BHMT1), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), and ATP synthase subunit beta, mitochondrial (ATP5B) density in the livers of male (A) and female (B) offspring. The number of samples (S) signify the protein density of the offspring in each group. The levels of expression of BHMT1, MTHFD1, and ATP5B were significantly reduced in the livers of the food-restricted (FR)/ad libitum (AdLib) male offspring (P<0.05, C) compared with those of the control group. The levels of BHMT1, MTHFD1, and ATP5B in the livers of female offspring did not differ among groups (D). Data are expressed as mean±standard deviation. ^a)P<0.05 compared with AdLib/AdLib; ^b),c)Significant difference of the protein expressions between sampe protein (P<0.05).

Fig. 8

A photomicrograph of male offspring livers in the 3 groups (A); the protein expression levels of mammalian target of rapamycin (mTOR) and sterol regulatory element-binding protein 1 (SREBP1) were measured by Western blotting in the 3 groups [60]. AdLib/FR, given an ad libitum diet during late gestation and an 50% food-restricted diet during lactation; cv, central vein; FR/AdLib, given a 50% food-restricted diet during late gestation and ad libitum diet during lactation. Data are present as mean±standard deviation. P-values indicate the significance of the differences among the groups (one-way analysis of variance). ^a)Control vs. FR/AdLib, FR/AdLib vs. AdLib/FR, control vs. AdLib/FR, P<0.05.