Review
Epigenetic mechanisms and the transgenerational effects of maternal care

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Abstract

The transmission of traits across generations has typically been attributed to the inheritance by offspring of genomic information from parental generations. However, recent evidence suggests that epigenetic mechanisms are capable of mediating this type of transmission. In the case of maternal care, there is evidence for the behavioral transmission of postpartum behavior from mothers to female offspring. The neuroendocrine and molecular mediators of this transmission have been explored in rats and implicate estrogen–oxytocin interactions and the differential methylation of hypothalamic estrogen receptors. These maternal effects can influence multiple aspects of neurobiology and behavior of offspring and this particular mode of inheritance is dynamic in response to environmental variation. In this review, evidence for the generational transmission of maternal care and the mechanisms underlying this transmission will be discussed as will the implications of this inheritance system for offspring development and for the transmission of environmental information from parents to offspring.

Introduction

Maternal effects have been demonstrated across many species and serve as an important cue to offspring development. In mammals, the lengthy period of prenatal and postnatal mother–infant interaction provides an opportunity for mothers to influence offspring through a variety of mechanisms. During gestation, interactions between mother and fetus are critical for growth and development and variations in these interactions can have long-term consequences for offspring physiological and psychological health. These effects have best been demonstrated through study of prenatal stress [133] and maternal malnutrition [9], [80] in which changes to the mother’s neuroendocrine system and physiology produces a shift in fetal neurodevelopment. Likewise, the care received by an infant early in life can produce changes in the development of neural systems regulating response to novelty and social behavior [84]. Thus, the maternal environment experienced by a developing organism can play a critical role in shaping adult patterns of behavior. Moreover, there can be transmission of these effects to subsequent generations through alterations in the reproductive behavior of offspring. Thus maternal care can be transmitted from mothers to daughters and grand-daughters. The mechanisms mediating this transmission have been explored in rodents and involve epigenetic alterations to steroid receptor genes that produce long-term changes in gene expression and behavior. In this review, the evidence for the context-dependent epigenetic transmission of reproductive behavior and the consequences of these generational effects on offspring development will be discussed. In addition, the role of environment in modulating the epigenetic effects of maternal care will be explored.

Section snippets

Matrilineal transmission of maternal care

In both humans and primates there is evidence for the matrilineal transmission of maternal behavior. In the case of child abuse, there is a striking trans-generational continuity in humans. It is currently estimated that up to 70% of abusive parents were themselves abused, whereas 20–30% of abused infants are likely to become abusers [25], [34]. Women reared in institutional settings without experiencing parental care display less sensitivity and are more confrontational towards their own

Influence of maternal care on offspring neurobiology and behavior

Taken together, these studies implicate a strong relationship between mother’s care and the maternal behavior of offspring. Data from cross-fostering studies conducted in primates and rodents suggests that this inheritance is not genetic, in the sense that it is not mediated by sequence variations in DNA, but rather is behavioral, relying on the quality of the postpartum mother–infant interaction. However, regardless of whether the etiology of this transmission is genetic or behavioral there

The neurobiology of maternal licking/grooming

Research on the neuroendocrine consequences of maternal LG for female offspring has focused primarily on systems related to the expression of maternal care itself. Activation of maternal care is thought to involve several nuclei including the bed nucleus of the stria terminalis (BNST), lateral septum (LS), and medial preoptic area (MPOA) [91], [94]. Evidence from neuroanatomical and hormonal manipulation of maternal care suggests that the MPOA in particular is essential for the expression of

Neuroendocrine effects of maternal LG on female offspring

In addressing the issue of the transmission of maternal care we must first understand the neuroendocrine systems in female offspring that are altered by maternal LG. As is the case with High- and Low-LG dams, the offspring of these females display altered levels of hypothalamic oxytocin receptor binding [20]. Thus, offspring of Low-LG dams have reduced oxytocin receptor binding during the postpartum period. Moreover, offspring of Low-LG dams that have been ovarietomized and given a high dose of

Mechanisms mediating long-term changes in gene expression

The experience of maternal LG in infancy clearly has enduring effects on neurobiology and behavior. Having described these effects, the question now becomes: “How are these long-term effects achieved?” Though infancy and adulthood are separated by a relatively short period of time in rodents compared to humans or primates, this is still a lengthy interval during which time offspring have been weaned from the mother and housed with peers. Determining the mechanisms capable of maintaining stable

Implications of the transgenerational effects maternal care

The behavioral transmission of maternal care across generations provides a mechanism for the transmission of other maternally mediated effects such as stress responsivity, cognitive ability, and response to reward. Thus both the offspring and grand-offspring of High-LG dams would be predicted to exhibit an attenuated behavioral and physiological response to stress. Interestingly, this transmission is also associated with epigenetic alterations to steroid receptors involved in stress

Environmental regulation of maternal care

The quality of maternal care provided by a female to offspring can clearly be influenced by early environmental experiences. In the 1950s and 1960s Harlow examined the impact of complete maternal deprivation on the development of rhesus macaques. Females who spent the first 6 months of postnatal life in isolation rearing conditions were found to display impairments in maternal behavior as adults [6], [53], [111], including high rates of abuse, neglect, and infanticide. In rodents, the effects of

Stress and maternal care

Psychosocial stress is an effective means for inducing a change in behavior. Amongst pregnant or postparturient females this change in behavior can result in profound alterations in offspring development. In the case of prenatal stress, the neuroendocrine basis for these effects has been studied extensively in rodents and may involve changes to both the gestational and postpartum environment. Psychosocial stress experienced by pregnant females activates the maternal

Tactile stimulation as a mediator of maternal effects in mammals

There is converging evidence that maternal LG can mediate the transmission of epigenetic changes to gene expression and behavior across generations and that the quality of the environment can influence frequency of LG and thus shape offspring development though variations in maternal care. However, not all species engage in LG and this form or maternal care is not typically observed in primates and humans. However, LG is also a very discrete form of tactile stimulation and though the form of

Summary

Traditionally, definitions of inheritance have been limited to the passing of genetic information from one generation to the next. However, it is not simply the presence of genes but rather levels of gene expression that lead to individual variations in offspring characteristics. Levels of gene expression can be regulated by genetic polymorphisms however there is also growing evidence that through epigenetic modification to gene promoter regions, environmentally mediated effects can be

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