Programming and reprogramming from conception till death

Abstract (PubMed)

During conception (fusion of maternal and paternal germ cells) a new entity is formed, which has individual structure and functions. From its gene-pool (genome) epigenetic regulation selects those genes which are durably or acutely working, supplying a theoretically lifelong program. However, this program could be changed spontaneously or artificially, and there are life periods when the spontaneous changes are especially frequent and the sensitivity to physiological or artificial (man-made) factors is high. The basic sensitive (most vulnerable) period is the perinatal one, when the program agglomerated (and this is manifested in the faulty hormonal imprinting and DOHaD theories: perinatal adverse effects can cause diseases in adults), however, later periods are also sensitive. Such rather sensitive periods are the puberty and periadolescence as well as weaning, nevertheless, in any periods of life, cells or cell groups could be epigenetically imprinted, if the cells are in the state of differentiation, independent of the age or developmental state of the complete organism. Earlier mainly natural molecules (products of volcanic eruptions or phytoestrogens, mykotoxins, tobacco) threatened the program, today man-made artificial molecules (endocrine disruptors) can reprogram the visibly stable program, by a single encounter with hormone receptors at the periods of sensitivity (faulty hormonal imprinting) with life-long consequences (altered cell functions, inclination to diseases, manifestation of diseases, etc., provoked by functional teratogens). The deformed program is inherited to the offspring generations, where further program transformations are taking place on the inherited (transformed) program. As the amount and variants of man-made endocrine disruptors are enormously growing in the human environment and its important parts act during the developmentally most sensitive periods, the diseases provoked by them in adults expectedly will be enormously accruing.