interactions within the nucleus. additionally, plants defective in components of the rna-directed dna-methylation pathway show an increased expression of b1 in b' individuals similar to that of b-i, however, once these components are restored, the plant reverts to the low expression state. although spontaneous conversion from b-i to b' has been observed, a reversion from b' to b-i (green to purple) has never been observed over 50 years and thousands of plants in both greenhouse and field experiments. examples of environmentally induced transgenerational epigenetic inheritance in plants has also been reported. in one case, rice plants that were exposed to drought-simulation treatments displayed increased tolerance to drought after 11 generations of exposure and propagation by single-seed descent as compared to non-drought treated plants. differences in drought tolerance was linked to directional changes in dna-methylation levels throughout the genome, suggesting that stress-induced heritable changes in dna-methylation patterns may be important in adaptation to recurring stresses. in another study, plants that were exposed to moderate caterpillar herbivory over multiple generations displayed increased resistance to herbivory in subsequent generations (as measured by caterpillar dry mass) compared to plants lacking herbivore pressure. this increase in herbivore resistance persisted after a generation of growth without any herbivore exposure suggesting that the response was transmitted across generations. the report concluded that components of the rna-directed dna-methylation pathway are involved in the increased resistance across generations. transgenerational epigenetic inheritance has also been observed in polyploid plants. genetically identical reciprocal f1 hybrid triploids have been shown to display transgenerational epigenetic effects on viable f2 seed development. it has been demonstrated in wild radish plants (raphanus raphanistrum) that tei can be induced when the plants are exposed to predators such as pieris rapae, the cabbage white caterpillar. the radish plants will increase production of bristly leaf hairs and toxic mustard oil in response to caterpillar predation. the increased levels will also be seen in the next generation. decreased levels of predation also results in decreased leaf hairs and toxins produced in the current and subsequent generations. in animals it is difficult to trace tei in animals due to the reprogramming of genes during meiosis and embryogenesis, especially in wild populations that are not reared in a lab setting. further studies must be conducted to strengthen the documentation of tei in animals. however, a few examples do exist. induced transgenerational epigenetic inheritance has been demonstrated in animals, such as daphnia cucullata. these tiny crustaceans will develop protective helmets as juveniles if exposed to kairomones, a type of hormone, secreted by predators while they are in utero. the helmet acts as a method of defense by decreasing the ability of predators to capture the daphnia, thus induction of helmet presence will lower mortality rates. d. cucullata will develop a small helmet if no kairomones are present. however, depending upon the level of predator kairomones, the length of the helmet will almost double. the next generation of daphnia will display a similar helmet size. if the kairomone levels decrease or disappear, then the third generation will revert to the original helmet size. these organisms display adaptive phenotypes that will affect the phenotype in the subsequent generations. genetic analysis of coral reef fish, acanthochromis polyacanthus, has proposed tei in response to climate change. as climate change occurs, the ocean water temperature increases. when a. polyacanthus is exposed to higher water temperatures of up to +3 °c from normal ocean temperatures, the fish express increased dna methylation levels on 193 genes, resulting in phenotypic changes in the function of oxygen consumption, metabolism, insulin response, energy production, and angiogenesis. the increase in dna methylation and its phenotypic affects were carried over to multiple subsequent generations. possible tei has been studied in guinea pigs (cavia aperea) by exposing males to increased ambient temperature for two months. in the lab, the males were allowed to mate with the same female before and after the heat exposure to determine if the high temperatures affected the offspring. since it serves as a thermoregulatory organ, samples of the liver were studied in the father guinea pigs (f0 generation) and liver and testes of the male offspring (f1 generation). the f0 males experienced an immediate epigenetic response to the increase in temperature; the levels of hormones in the liver responsible for thermoregulation increased. the f1 generation also displayed the different methylated epigenetic response in their liver and testes, indicating that they could potentially pass on the epigenetic marks to the f2 generation. in humans although genetic inheritance is important when describing phenotypic outcomes, it cannot entirely explain why offspring resemble their parents. aside from genes, offspring come to inherit similar environmental conditions established by previous generations. one environment that human offspring commonly share with their maternal parent for nine months is the womb. considering the duration of the fetal stages of development, the environment of the mother’s womb can have long lasting effects on the health of offspring. an example of how the environment within the womb can affect the health of an offspring is the dutch hunger winter of 1944-45 and its causal effect on induced transgenerational epigenetic inherited diseases. during the dutch hunger winter, the offspring exposed to famine conditions during the third trimester of development were smaller than those born the year before the famine. moreover, the offspring born during the famine and their subsequent offspring were found to have an increased risk of metabolic diseases, cardiovascular diseases, glucose intolerance, diabetes, and obesity in adulthood. the effects of this famine on development lasted up to two generations. the increased risk factors to the health of f1 and f2 generations during the dutch hunger winter is a known phenomenon called “fetal programming,” which is caused by exposure to harmful environmental factors in utero. the loss of genetic expression which results in prader–willi syndrome or angelman syndrome has in some cases been found to be caused by epigenetic changes (or "epimutations") on both the alleles, rather than involving any genetic mutation. in all 19 informative cases, the epimutations that, together with physiological imprinting and therefore silencing of the other allele, were causing these syndromes were localized on a chromosome with a specific parental and grandparental origin. specifically, the paternally derived chromosome carried an abnormal maternal mark at the snurf-snrpn, and this abnormal mark was inherited from the paternal grandmother. several cancers have been found to be influenced by transgenerational epigenetics. epimutations on the mlh1 gene has been found in two individuals with a phenotype of hereditary nonpolyposis colorectal cancer, and without any frank mlh1 mutation which otherwise causes the disease. the same epimutations were also found on the spermatozoa of one of the individuals, indicating the potential to be transmitted to offspring. in addition to epimutations to the mlh1 gene, it has been determined that certain cancers, such as breast cancer, can originate during the fetal stages within the uterus. furthermore, evidence collected in various studies utilizing model systems (i.e. animals) have found that exposure during parental generations can result in multigenerational and transgenerational inheritance of breast cancer. more recently, studies have discovered a connection between the adaptation of male germinal cells via pre-conception paternal diets and the regulation of breast cancer in developing offspring. more specifically, studies have begun to uncover new data that underscores a relationship between transgenerational epigenetic inheritance of breast cancer and ancestral alimentary components or associated markers, such as birth weight. by utilizing model systems, such as mice, studies have shown that stimulated paternal obesity at the time of conception can epigenetically alter the paternal germ-line. the paternal germ-line is responsible for regulating their daughters’ weight at birth and the potential for their daughter to develop breast cancer. furthermore, it was found that modifications to the mirna expression profile of the male germline is coupled with elevated body weight. additionally, paternal obesity resulted in an increase in the percentage of female offspring developing carcinogen-induced mammary tumors, which is caused by changes to mammary mirna expression. aside from cancer related afflictions associated with the effects of transgenerational epigenetic inheritance, transgenerational epigenetic inheritance has recently been implicated in the progression of pulmonary arterial hypertension (pah). recent studies have found that transgenerational epigenetic inheritance is likely to be involved in the progression of pah because current therapies for pah do not repair the irregular phenotypes associated with this disease. current treatments for pah have attempted to correct symptoms of pah with vasodilators and antithrombotic protectors, but neither has effectively alleviated the complications related to the impaired phenotypes associated with pah. the inability of vasodilators and antithrombotic protectants to correct pah suggests that the progression of pah is dependent upon multiple variables, which is likely to be consequent of transgenerational epigenetic inheritance. specifically, it is thought that transgenerational epigenetics is linked to the phenotypic changes associated with vascular remodeling. for example, hypoxia during gestation may induce transgenerational epigenetic alterations that could prove to be detrimental during the early phases of fetal development and increase the possibility of developing pah as an adult. though hypoxic states could induce the transgenerational epigenetic variance associated with pah, there is strong evidence to support that a variety of maternal risk factors are linked to the eventual progression of pah. such maternal risk factors linked to late-onset pah includes placental dysfunction, hypertension, obesity, and preeclampsia. these maternal risk factors and environmental stressors coupled with transgenerational epigenetic changes can result in prolonged insult to the signaling pathways associated with the vascular development during fetal stages, thus increasing the likelihood of having pah. one study has shown childhood abuse, which is defined as "sexual contact, severe physical abuse and/or severe neglect," leads to epigenetic modifications of glucocorticoid receptor expression. glucocorticoid receptor expression plays a vital role in hypothalamic-pituitary-adrenal (hpa) activity. additionally, animal experiments have shown that epigenetic changes can depend on mother-infant interactions after birth. furthermore, a recent study investigating the correlations between maternal stress in pregnancy and methylation in teenagers/their mothers has found that children of women who were abused during pregnancy were more likely to have methylated glucocorticoid-receptor genes. thus, children with methylated glucocorticoid-receptor genes experience an altered response to stress, ultimately leading to a higher susceptibility of experiencing anxiety. additional studies examining the effects of diethylstilbestrol (des), which is an endocrine disruptor, have found that the grandchildren (third-generation) of women exposed to des significantly increased the probability of their grandchildren developing attention-deficit/hyperactivity disorder (adhd). this is because women exposed to endocrine disruptors, such as des, during gestation may be linked to multigenerational neurodevelopmental deficits. furthermore, animal studies indicate that endocrine disruptors have a profound impact on germline cells and neurodevelopment. the cause of des's multigenerational impact is postulated to be the result of biological processes associated with epigenetic reprogramming of the germline, though this has yet to be determined. effects on fitness epigenetic inheritance may only affect fitness if it predictably alters a trait under selection. evidence has been forwarded that environmental stimuli are important agents in the alteration of epigenes. ironically, darwinian evolution may act on these neo-lamarckian acquired characteristics as well as the cellular mechanisms producing them (e.g. methyltransferase genes). epigenetic inheritance may confer a fitness benefit to organisms that deal with environmental changes at intermediate timescales. short-cycling changes are likely to have dna-encoded regulatory processes, as the probability of the offspring needing to respond to changes multiple times during their lifespans is high. on the other end, natural selection will act on populations experiencing changes on longer-cycling environmental changes. in these cases, if epigenetic priming of the next generation is deleterious to fitness over most of the interval (e.g. misinformation about the environment), these genotypes and epigenotypes will be lost. for intermediate time cycles, the probability of the offspring encountering a similar environment is sufficiently high without substantial selective pressure on individuals lacking a genetic architecture capable of responding to the environment. naturally, the absolute lengths of short, intermediate, and long environmental cycles will depend on the trait, the length of epigenetic memory, and the generation time of the organism. much of the interpretation of epigenetic fitness effects centers on the hypothesis that epigenes are important contributors to phenotypes, which remains to be resolved. deleterious effects inherited epigenetic marks may be important for regulating important components of fitness. in plants, for instance, the lcyc gene in linaria vulgaris controls the symmetry of the flower. linnaeus first described radially