When a woman becomes pregnant, her body undergoes
many changes. Some are caused by increased levels of
the hormones prolactin, estrogen, and progesterone.
Among the most significant changes are those in the
mammary gland, the organ that produces milk.
Several studies have shown that humans and other
mammals produce more milk during second pregnancies
than first pregnancies. This suggests that the first
pregnancy causes a long-lasting change in the
mammary gland. However, the structure of the mammary
gland is virtually identical in previously pregnant
(or “parous”) and never-pregnant (non-parous)
animals. One possibility for how this change might
occur is that pregnancy alters the organ’s epigenome,
the collection of chemical markers that affect how
genes are turned on and off, or expressed..
Researchers led by Dr. Gregory J. Hannon at Cold
Spring Harbor Laboratory explored this idea. Their
work was funded by in part by NIH’s National Cancer
Institute (NCI) and National Human Genome Research
Institute (NHGRI). The study was published in Cell
Reports on May 19, 2015.
The researchers first examined the effects of
pregnancy hormones on parous and non-parous mice.
They exposed mice to estrogen and progesterone at
levels similar to those found during pregnancy. They
found that the mammary glands of parous mice
developed more quickly and showed signs of milk
production earlier than those of non-parous mice.
Next, the team looked at how pregnancy affects a
type of epigenetic mark called DNA methylation. In
mice that had been pregnant or received
pregnancy-related hormones, many genes in mammary
gland cells had reduced DNA methylation. The changes
in DNA methylation in cells involved in milk
production were different from those in cells that
don’t produce milk. These changes were still present
several months later.
The researchers found that the decreased methylation
increased the expression of many genes, but only
when the mice were exposed to pregnancy-related
hormones. This suggests that these changes in DNA
methylation only affect gene expression when an
animal is pregnant.
Most of the decreased methylation occurred in areas
of the genome bound by a transcription factor
protein called Stat5a. Transcription factors bind to
specific DNA sequences and influence the expression
of genes. These findings imply that
pregnancy-related changes in DNA methylation alter
gene expression by influencing the action of Stat5a.
“This is an example of epigenetic memory: it is the
loss of DNA methylation that is now marking sites in
the genome that were active in a previous
pregnancy,” says study coauthor Dr. Camila dos
Santos.
The researchers are now examining whether similar
epigenetic changes might also help explain why
pregnancy reduces women’s risk of breast cancer
later in life.
For more information
An Epigenetic Memory of Pregnancy in the Mouse
Mammary Gland
Dos Santos CO, Dolzhenko E, Hodges E, Smith AD,
Hannon GJ. Cell Rep. 2015 May 19;11(7):1102-9.
doi: 10.1016/j.celrep.2015.04.015. Epub 2015 May
7. PMID: 25959817.
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