[OEM] Science/WashSt.U: Toxins in Inherited Disease (fwd)

[Guest guest]

and this is NEW??????

http://www.wsunews.wsu.edu/detail.asp?StoryID=5261

Washington State University Study Points to Role of Toxins in Inherited Disease

PULLMAN, Wash. -- A disease you are suffering today could be a resultof your

great-grandmother being exposed to an environmental toxinduring pregnancy.

Researchers at Washington State University reached that remarkableconclusion

after finding that environmental toxins can alter theactivity of an animal's

genes in a way that is transmitted through atleast four generations after the

exposure. Their discovery suggeststhat toxins may play a role in heritable

diseases that were previouslythought to be caused solely by genetic mutations.

It also hints at arole for environmental impacts during evolution.

" It's a new way to think about disease, " said K. Skinner,director of

the Center for Reproductive Biology. " We believe thisphenomenon will be

widespread and be a major factor in understandinghow disease develops. "

The work is reported in the June 3 issue of Science Magazine.

Skinner and a team of WSU researchers exposed pregnant rats toenvironmental

toxins during the period that the sex of their offspringwas being determined.

The compounds – vinclozolin, a fungicidecommonly used in vineyards, and

methoxychlor, a pesticide thatreplaced DDT – are known as endocrine

disruptors, synthetic chemicalsthat interfere with the normal functioning of

reproductive hormones.

Skinner's group used higher levels of the toxins than are normallypresent in

the environment, but their study raises concerns about thelong-term impacts of

such toxins on human and animal health. Furtherwork will be needed to determine

whether lower levels have similareffects.

Pregnant rats that were exposed to the endocrine disruptors producedmale

offspring with low sperm counts and low fertility. Those maleswere still able

to produce offspring, however, and when they weremated with females that had

not been exposed to the toxins, their maleoffspring had the same problems. The

effect persisted through allgenerations tested, with more than 90 percent of

the male offspring ineach generation affected. While the impact on the first

generation wasnot a surprise, the transgenerational impact was unexpected.

Scientists have long understood that genetic changes persist

throughgenerations, usually declining in frequency as the mutated form of agene

gets passed to some but not all of an animal's offspring. Thecurrent study

shows the potential impact of so-called epigeneticchanges.

Epigenetic inheritance refers to the transmission from parent tooffspring of

biological information that is not encoded in the DNAsequence. Instead, the

information stems from small chemicals, such asmethyl groups, that become

attached to the DNA. In epigenetictransmission, the DNA sequences – the genes –

remain the same, but thechemical modifications change the way the genes work.

Epigeneticchanges have been observed before, but they have not been seen to

passto later generations.

While this research focused on the impact of these changes on malereproduction,

the results suggested that environmental influencescould have multigenerational

impacts on heritable diseases. Accordingto Skinner, epigenetic changes might

play a role in diseases such asbreast cancer and prostate disease, whose

frequency is increasingfaster than would be expected if they were the result of

geneticmutations alone.

The finding that an environmental toxin can permanently reprogram aheritable

trait also may alter our concept of evolutionary biology.Traditional

evolutionary theory maintains that the environment isprimarily a backdrop on

which selection takes place, and thatdifferences between individuals arise from

random mutations in theDNA. The work by Skinner and his group raises the

possibility thatenvironmental factors may play a much larger role in evolution

thanhas been realized before. This research was supported in part by agrant to

Skinner from the U.S. Environmental Protection Agency's STARProgram.

Related Web sites:WSU Center for Reproductive Biology

http://www.crb.wsu.edu/ Skinner's Web site: www.skinner.wsu.eduWSU

Research News and Features: http://researchnews.wsu.edu

= - = - = - = - = - = - = - = - = - = - Science, Vol 308, Issue 5727, 1466-1469

, 3 June 2005

ReportsEpigenetic Transgenerational Actions of Endocrine Disruptors and Male

Fertility D. Anway, S. Cupp,* Mehmet Uzumcu, K. Skinner

Transgenerational effects of environmental toxins require either achromosomal

or epigenetic alteration in the germ line. Transientexposure of a gestating

female rat during the period of gonadal sexdetermination to the endocrine

disruptors vinclozolin (anantiandrogenic compound) or methoxychlor (an

estrogenic compound)induced an adult phenotype in the F1 generation of

decreasedspermatogenic capacity (cell number and viability) and

increasedincidence of male infertility. These effects were transferred

throughthe male germ line to nearly all males of all subsequent

generationsexamined (that is, F1 to F4). The effects on reproduction

correlatewith altered DNA methylation patterns in the germ line. The ability

ofan environmental factor (for example, endocrine disruptor) toreprogram the

germ line and to promote a transgenerational diseasestate has significant

implications for evolutionary biology anddisease etiology.

Center for Reproductive Biology, School of Molecular Biosciences,Washington

State University, Pullman, WA 99164–4231, USA.

* Present address: Department of Animal Science, University ofNebraska,

Lincoln, NE 68583–0908, USA.

Present address: Department of Animal Science, Rutgers University, 84Lipman

Drive, New Brunswick, NJ 08901–8525, USA.

To whom correspondence should be addressed. E-mail: skinner@...

[Guest guest]

Angel,

Great find. Many of us have been discussing this for the last couple

of years. It looks like it is finally coming to light, just another

piece of the puzzle. Is this why many generations experience the

same type of cancer after being exposed to some form of

environmental toxins? I can't believe it took 'um them long.

KC

--- In , Angel MCS <jap2bemc@s...>

wrote:

>

> and this is NEW??????

>

>

> http://www.wsunews.wsu.edu/detail.asp?StoryID=5261

> Washington State University Study Points to Role of Toxins in

Inherited Disease

> PULLMAN, Wash. -- A disease you are suffering today could be a

resultof your

> great-grandmother being exposed to an environmental toxinduring

pregnancy.

> Researchers at Washington State University reached that

remarkableconclusion

> after finding that environmental toxins can alter theactivity of

an animal's

> genes in a way that is transmitted through atleast four

generations after the

> exposure. Their discovery suggeststhat toxins may play a role in

heritable

> diseases that were previouslythought to be caused solely by

genetic mutations.

> It also hints at arole for environmental impacts during evolution.

> " It's a new way to think about disease, " said K.

Skinner,director of

> the Center for Reproductive Biology. " We believe thisphenomenon

will be

> widespread and be a major factor in understandinghow disease

develops. "

> The work is reported in the June 3 issue of Science Magazine.

> Skinner and a team of WSU researchers exposed pregnant rats

toenvironmental

> toxins during the period that the sex of their offspringwas being

determined.

> The compounds – vinclozolin, a fungicidecommonly used in

vineyards, and

> methoxychlor, a pesticide thatreplaced DDT – are known as

endocrine

> disruptors, synthetic chemicalsthat interfere with the normal

functioning of

> reproductive hormones.

> Skinner's group used higher levels of the toxins than are

normallypresent in

> the environment, but their study raises concerns about thelong-

term impacts of

> such toxins on human and animal health. Furtherwork will be needed

to determine

> whether lower levels have similareffects.

> Pregnant rats that were exposed to the endocrine disruptors

producedmale

> offspring with low sperm counts and low fertility. Those maleswere

still able

> to produce offspring, however, and when they weremated with

females that had

> not been exposed to the toxins, their maleoffspring had the same

problems. The

> effect persisted through allgenerations tested, with more than 90

percent of

> the male offspring ineach generation affected. While the impact on

the first

> generation wasnot a surprise, the transgenerational impact was

unexpected.

> Scientists have long understood that genetic changes persist

> throughgenerations, usually declining in frequency as the mutated

form of agene

> gets passed to some but not all of an animal's offspring.

Thecurrent study

> shows the potential impact of so-called epigeneticchanges.

> Epigenetic inheritance refers to the transmission from parent

tooffspring of

> biological information that is not encoded in the DNAsequence.

Instead, the

> information stems from small chemicals, such asmethyl groups, that

become

> attached to the DNA. In epigenetictransmission, the DNA sequences –

the genes –

> remain the same, but thechemical modifications change the way the

genes work.

> Epigeneticchanges have been observed before, but they have not

been seen to

> passto later generations.

> While this research focused on the impact of these changes on

malereproduction,

> the results suggested that environmental influencescould have

multigenerational

> impacts on heritable diseases. Accordingto Skinner, epigenetic

changes might

> play a role in diseases such asbreast cancer and prostate disease,

whose

> frequency is increasingfaster than would be expected if they were

the result of

> geneticmutations alone.

> The finding that an environmental toxin can permanently reprogram

aheritable

> trait also may alter our concept of evolutionary

biology.Traditional

> evolutionary theory maintains that the environment isprimarily a

backdrop on

> which selection takes place, and thatdifferences between

individuals arise from

> random mutations in theDNA. The work by Skinner and his group

raises the

> possibility thatenvironmental factors may play a much larger role

in evolution

> thanhas been realized before. This research was supported in part

by agrant to

> Skinner from the U.S. Environmental Protection Agency's

STARProgram.

> Related Web sites:WSU Center for Reproductive Biology

> http://www.crb.wsu.edu/ Skinner's Web site:

www.skinner.wsu.eduWSU

> Research News and Features: http://researchnews.wsu.edu

> = - = - = - = - = - = - = - = - = - = - Science, Vol 308, Issue

5727, 1466-1469

> , 3 June 2005

> ReportsEpigenetic Transgenerational Actions of Endocrine

Disruptors and Male

> Fertility D. Anway, S. Cupp,* Mehmet Uzumcu,

K. Skinner

> Transgenerational effects of environmental toxins require either

achromosomal

> or epigenetic alteration in the germ line. Transientexposure of a

gestating

> female rat during the period of gonadal sexdetermination to the

endocrine

> disruptors vinclozolin (anantiandrogenic compound) or methoxychlor

(an

> estrogenic compound)induced an adult phenotype in the F1

generation of

> decreasedspermatogenic capacity (cell number and viability) and

> increasedincidence of male infertility. These effects were

transferred

> throughthe male germ line to nearly all males of all subsequent

> generationsexamined (that is, F1 to F4). The effects on

reproduction

> correlatewith altered DNA methylation patterns in the germ line.

The ability

> ofan environmental factor (for example, endocrine disruptor)

toreprogram the

> germ line and to promote a transgenerational diseasestate has

significant

> implications for evolutionary biology anddisease etiology.

> Center for Reproductive Biology, School of Molecular

Biosciences,Washington

> State University, Pullman, WA 99164–4231, USA.

> * Present address: Department of Animal Science, University

ofNebraska,

> Lincoln, NE 68583–0908, USA.

> Present address: Department of Animal Science, Rutgers University,

84Lipman

> Drive, New Brunswick, NJ 08901–8525, USA.

> To whom correspondence should be addressed. E-mail: skinner@m...

>

>

>

>