be biologically transmitted across generations through the uterine environment. gestational development is not only critical for traditional organ/fetus development, but also sets the stage for neural and behavioral development. exposure to harmful stimuli during this stage can have long-lasting, detrimental effects and the uterine environment with its unique blend of the mother's cellular secretions and proteins can be a major source of such stimuli. empirical evidence has shown that trauma experienced by a mother during pregnancy can affect her children's long-term physiology and psychology, as antenatal maternal anxiety is associated with an increased risk for the development of neuropsychiatric disorders such as depression and anxiety in teenage offspring. the increased risk of these psychiatric disorders has been linked to changes in dna expression due to epigenetic alterations in dna methylation patterns in utero. research shows that epigenetic changes can be observed in genes associated with the hypothalamic-pituitary-adrenal (hpa) axis, which coordinates the body's stress response system. the glucocorticoids, including cortisol, are neurohormones triggered by stress which trigger the "fight-or-flight" response which includes increased blood pressure and heart rate. nr3c1 is a gene that codes for glucocorticoid receptors. in rodent studies, it was found that the pups born to neglectful mothers showed increased methylation in the nr3c1 gene compared to those with high grooming mothers. increased expression of this glucocorticoid receptor due to demethylation of the gene leads to a decrease in the offspring's stress response. pups born to a low licking and grooming mother but raised by a high licking-grooming mother had less nr3c1 gene methylation thus lower stress levels. this shows that maternal grooming behavior is responsible for the changed methylation state of the glucocorticoid receptor. findings show that the grooming is linked with demethylation of the nr3c1 gene, which increased glucocorticoid receptor expression resulting in decreased stress levels in the mice. these cross-fostered pups were found to be indistinguishable from the pups born and raised by neglectful mothers or high grooming mothers. in animal models, maternal stress and trauma during pregnancy has been shown to reduce the expression of placental enzyme 11b-hydroxysteroid dehydrogenase type 2 (11 β-hsd2), which converts the mother's cortisol to inactive cortisone. this leads to increased fetal exposure to the mother's glucocorticoids, which affects the development of glucocorticoid-sensitive systems like the hpa axis. in some studies, abnormal cortisol levels compared to controls and alterations in dna methylation were observed in infants of mothers who endured trauma while pregnant, particularly in the nr3c1 glucocorticoid receptor gene. another possible method of transmission is through transport vesicles transferring amino acids and microrna from the uterine fluid to the fetus. these molecules may then alter gene expression in a way that affects the developmental trajectory of the fetus. hormones such as leptin and insulin, as well as nutrients, trigger the regulation of amino acid transporters in the placenta. amino acid transport is necessary for fetal growth, and its restriction can have life-long effects on the offspring's health. amino acid transport is also regulated by dna methylation of amino acid transporter genes, modifying their expression in the placenta throughout the fetus's development. there are questions of whether transmission occurs via maternal care or in utero changes, or perhaps both. a study by alhassen et al. found that female mice who were exposed to a predator's scent, thus inducing stress, were more likely to rear pups who expressed depressive-like behaviors and social deficits. however, non-traumatized mothers' maternal care was not sufficient enough to reverse prenatal trauma-induced behavior. this effect was linked to changes in the brain metabotranscriptome of their offspring, which were significantly different from the pups from mothers who did not experience trauma. the study finds that a large upregulation in 2-hydroxyglutaric acid in pups and adults exposed to trauma prenatally induces changes in epigenetic mechanisms and mitochondrial function. in their model, 2-hydroxyglutaric acid is upregulated due to hypoxic conditions prenatally, as the mother during her fight-or-flight response has less oxygen delivered to the pups. researchers were able to counteract long-term intergenerational trauma-induced depression using acetyl-l-carnitine, which counteracts the prenatal modifications in many mechanisms which stem from hypoxia. there have been other animal studies reporting the link between adverse childhood experiences and epigenetic modifications. although these studies were in mammal animal models, they study epigenetic mechanisms that may occur in humans as well. three of those and their findings are mentioned below: similar to the study above, reduced methylation of the glucocorticoid receptor gene was found in the offspring of high-licking canine mothers. in contrast, offspring that face early adversity exhibit endocrine dysregulation, as well as reductions in neuronal plasticity in the prefrontal cortex (pfc) that persist into adulthood. another study provides evidence of increased methylation of stress-response genes including brain-derived neurotrophic factor and nuclear protein phosphate-1 in neurons in rats who exhibit ptsd-like behavior. and one particular study, mcgowan et al., the "subject group was suicide completers, which reported that childhood abuse was associated with greater methylation levels at cpg sites in the exon1f of the promoter region of the glucocorticoid receptor gene." this study examined epigenetic modifications in neurons but did not provide insight into links of adverse childhood experiences and epigenetic modifications. research has also been conducted on mothers who were pregnant on 9/11. cortisol levels between pregnant mothers who did not develop ptsd due to the event versus pregnant mothers who did develop ptsd indicate that the latter group had a decrease in cortisol levels. furthermore, children of these mothers who developed ptsd also had lower cortisol levels. low cortisol is previously known to increase the risk for ptsd, so the fact that both mother, after traumatic exposure, and the child, presumably due to maternal stress levels, had lower cortisol suggests some sort of epigenetic modification to cortisol levels was made during the traumatic event that was able to be passed down. it was also found that children whose mothers lived close to the world trade center had higher levels of stress agents in their saliva. altogether these studies suggest an intergenerational transmission of trauma that creates a higher susceptibility to ptsd in the child due to lower cortisol levels. the development of ptsd due to parental ptsd was also studied in adult offspring of holocaust survivors. here, researchers also found a link between enhanced suppression of cortisol found via urinary samples and saliva samples and parental ptsd. the fetal environment is influenced by the maternal diet. this environmental history can cause the fetal developmental response to change to produce a metabolic phenotype that suits the anticipated environment. epigenetic effects of nutrition include the methylation of genes involved in energy metabolism, anti-inflammatory processes, and tumor suppression. studies examine gestational diabetes mellitus (gdm), a condition where the mother experiences insulin resistance during pregnancy to avoid low blood glucose levels. this is a response to the shift of nutrients from the mother to the fetus. gdm results in maternal hyperglycemia, fetal hyperinsulinism, and fetal overnutrition. epigenetic mechanisms dna methylation can act as the mechanism for the transmission of intergenerational trauma. methylation typically takes place at relevant cpg islands and maintains its transcriptional repression effect across cell divisions, but can also be dynamically regulated. dna methylation has been found to be significant in regulating fear memory via methylation of immediate early genes (iegs) in the hippocampus dentate gyrus of mice models. histones can be modified via acetylation, methylation, phosphorylation, and sumoylation. acetyl and phosphate groups, which are modifiers typically associated with an upregulation of gene expression, attach onto lysine, serine, threonine, and tyrosine residues of histones. methylation (on lysine or arginine residues) and ubiquitylation (on lysine residues of histones h2a and h2b) are associated with both activating and repressing genes. sumo stands for small ubiquitin-like modifier and it binds to lysine residues. sumoylation is widely associated with repression and is also typically found with other epigenetic modifiers. these histone modifications alter the structure of chromatin, thus affecting the transcription of the genes associated with the altered histones. many post-translational modifications are affected by acute and chronic stress via glucocorticoid cascades. another pre-clinical study finds that the use of histone deacetylase inhibitors can aid in "exposure-based approaches in anxiety and trauma therapy". histone deacetylase inhibitors block the deacetylation of histones, which then allows genes to remain active by preserving the active acetyl mark on the histone on the dna. in the context of anxiety and trauma therapy, this allows the preservation of a long-term extinction memory that is able to replace the traumatic memory. histone deacetylase inhibited the formation of an extinction memory which consequently preserved the fearful memory, and by inhibiting it individuals in exposure therapy are able to create new memories with harmless or safe associations to their traumatic memory. non-coding rnas, or ncrnas, have been seen altering gene expression and being responsive to traumatic stress. mirnas, or micro rnas, can be used to silence genes via the risc complex. they are able to degrade mrna targets thus repressing translation of a gene. in ptsd studies, mirnas were found to be involved in responding to trauma. some evidence also supports long non-coding rna, lncrna, and piwi-interacting rna, pirna, being affected by trauma. post-transcriptional rna modifications are generally known to alter the folding of rna as well as their affinity for complementary strands. not much is known about it and its role in altering gene expression post-trauma, but there has been evidence of contextual fear conditioning altering fto mrna, that encodes an rna demethylase. this suggests rna modifications may have been altered in response to this fear conditioning and may play a role in altering gene expression in response to trauma. psychological and social aspects there are many current transgenerational studies that have been done on adults that have experienced natural disasters or adversities. one study found that the children of torture victims showed more symptoms of anxiety, depression, post‐traumatic stress, attention deficits and behavioral disorders compared with the comparison group of those who had not experienced the specific trauma. a qualitative study was done on the brazilian children of holocaust survivors. this study was able to propose not only a supported model of the transgenerational transmission of traumatic experiences, but one also of resilience patterns that can be transmitted in between generations and developed within generations. according to froma walsh, resilience theory suggests that individuals' and families' responses to traumatic experiences is an ever-changing process that involves both exposure to challenges and the development of coping mechanisms that aide in one's ability to overcome such challenges. regardless of risk, there also exists opportunities for the development of resilience via exposure to meaningful resources that support one's ability to overcome adversity. researchers cowan, callaghan, & richardson studied the impact of early-life adversities on individuals and their descendants. their research was also consistent with the transmission theory, in which their findings revealed that the stress phenotype that was expressed in individuals who experienced the adversity was also observed in children and even grandchildren. the famous study of harlow's monkeys also revealed that the adversity of a maternal variable which would create stress in the individual was also witnessed in their offspring although not having experienced the adversity. one last study displayed that if children were exposed to high postnatal maternal licking/grooming and arched-back nursing then they were likely to do the same to their offspring. vice versa, if children experienced low lg-abn mothers, then they were likely to provide the same to their offspring. consequently, this causes a decrease in serotonin and expression, and an increase in methylation. ultimately, a more stressed pup is created, causing this phenotype to be passed on through experience and genes. theses studies allude to the fact that oftentimes adversity, especially early on and for longer periods of time, can impact development in individuals and their offspring. the oppression that black people experienced through slavery and racism has a psychological impact on how they view achievement. in terms of the social aspects of this, seem to make it difficult for black people to surpass a certain ses threshold, to escape a certain neighborhood, to move beyond a certain lifestyle or status. for native americans, past government policy and internal displacements are theorized to have an effect generations later. the social enforcement of their ostracization causes them to be generally removed from society, to be powerless and uninvited in government, and to be left