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Science News from research organizations
Mammary gland 'remembers' priorpregnancy, spurring milk
production
May 7, 2015
Cold Spring Harbor Laboratory
Anecdotal reports of nursing mothers have long suggestedthat
giving milk is a lot easier in second and subsequentpregnancies,
compared with a first pregnancy. Now,researchers can explain why.
Their work shows themammary gland forms a long-term memory of
pregnancy thatprimes it to respond to the hormonal changes that
announcesucceeding pregnancies.
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succeeding pregnancies.
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FULL STORY
These images show the effect of pregnancy hormones after 6 and
12days on breast tissue in mice that have never been pregnant (top
row)and mice that have been pregnant once before (bottom row).
The
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mammary gland in previously pregnant mice responds earlier
andproduces more branching ductal structures, used in lactation.
Newresearch shows breast tissue retains a cellular memory of
priorpregnancy that makes response more rapid and vigorous in
subsequentpregnancies.
Credit: Image courtesy of Cold Spring Harbor Laboratory
Anecdotal reports of nursing mothers have longsuggested that
giving milk is a lot easier in secondand subsequent pregnancies,
compared with a firstpregnancy. Now, researchers at Cold
SpringHarbor Laboratory (CSHL) are able to explain why.
Their work shows the mammary gland forms a long-term memory
ofpregnancy that primes it to respond to the hormonal changes
thatannounce succeeding pregnancies. The memory lasts throughout
anindividual's reproductive years. The results appear online in
Cell Reports.
Secretion of the hormones estrogen and progesterone set the
stage fordramatic changes that take place in the breast during
pregnancy: amassive proliferation of mammary epithelial cells, and
the formation ofthousands of ductal structures, which support milk
production and transportduring lactation.
A team led by HHMI Investigator Greg Hannon, a CSHL Professor
and alsoa Professor and Senior Group Leader at the CRUK Cambridge
Institute atthe University of Cambridge, hypothesized that
pregnancy might alter the
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gland's receptiveness to pregnancy-related hormones.
Specifically, theysought to determine if this might occur via
changes in a set of chemicalmarks that attach to DNA, the genetic
material. Such marks -- molecules ofmethyl (CH3), for instance --
are called epigenetic marks, and theirpresence or absence in
particular locations in the genome can eitherprevent genes from
being expressed, or promote their expression.
Camila dos Santos, now a CSHL Assistant Professor, developed
atechnique critical to the newly reported experiments when she was
apostdoctoral investigator in the Hannon lab. Dos Santos found a
marker ofmammary stem cells that enabled her to isolate highly
purified stem cells inaddition to a number of other cell types
specific to the mouse mammarygland -- six in all. From these, she
generated genome-wide profiles ofwhere methyl groups attach to the
DNA. Of all the epigenetic marks, methylmarks tend to be the
longest lasting, and are often permanent.
Working with Andrew Smith, a computational biologist from the
University ofSouthern California, they found that cells sampled
from young mice thathad been through a single pregnancy cycle had
methylation marks thatwere "substantially different" from marks in
cells sampled from mice of thesame age that had never been
pregnant. "Of those changes," saysHannon, "we were able to trace a
majority to places in the genome where asingle transcription
factor, called Stat5a, binds. This is really remarkable --so many
changes in methylation, and you can track them down to a
singlefactor." Like all transcription factors, Stat5a binds to DNA
and in so doingchanges the way a specific gene or genes are
expressed.
The team shows that a first pregnancy erases many methyl marks
that arepresent throughout life leading up to pregnancy. During a
first pregnancy,the team suggests, Stat5a binds DNA in certain
types of mammaryepithelial cells, at places near genes that need to
be activated during
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pregnancy -- specifically, genes involved in proliferation and
lactation. Asthe team showed in mice, when a once-pregnant female
receiveshormones whose action simulates a real pregnancy, the mice
respondmore rapidly than other, never-pregnant mice given the same
hormones. Inthe previously pregnant mice, "the mammary glands start
expanding fasterand also sooner than for those experiencing
pregnancy hormones for thefirst time," says dos Santos. "It's as if
the gland already knows thosehormones."
"This is an example of epigenetic memory: it is the loss of DNA
methylationthat is now marking sites in the genome that were active
in a previouspregnancy," dos Santos says. When the same sites were
examined a yearafter pregnancy (or exposure to pregnancy hormones),
they remainedunoccupied by methyl marks. "The cell is not
replenishing DNA methylationat these sites, even after several cell
divisions, which means the memory ofprevious pregnancy is
long-term."
These findings have led to another important line of research.
It is wellknown that women who become pregnant by age 25 have
substantiallylower rates of breast cancer than women who bear
children later in life ornot at all. It is possible that the
implied protective factor is in some wayrelated to the epigenetic
memory of mammary cells just discovered,Hannon says.
Dos Santos says her lab is now "trying to understand which of
themodifications we found in this study might prevent development
of breastcancer in a pregnancy-related manner."
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Cite This Page :
Cold Spring Harbor Laboratory. "Mammary gland 'remembers'
priorpregnancy, spurring milk production." ScienceDaily.
ScienceDaily, 7 May2015. .
The above story is based on materials provided by Cold Spring
HarborLaboratory. The original article was written by Peter Tarr.
Note: Materialsmay be edited for content and length.
Journal Reference :
1. Gregory J. Hannon et al. An Epigenetic Memory of Pregnancy
inthe Mouse Mammary Gland. Cell Reports, May 2015
DOI:10.1016/j.celrep.2015.04.015
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