Fertility Road Issue 44 May/June 2018
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FR News & Views UCLA RESEARCH MAY EXPLAIN SOME CAUSES OF INFERTILITY AND MISCARRIAGE STUDY EXAMINES HOW EARLY EMBRYONIC DEVELOPMENT CAN GO AWRY A new study in the journal Nature Cell Biology has uncovered information about a key stage that human embryonic cells must pass through just before an embryo implants. The research, led by UCLA biologist Amander Clark, could help explain certain causes of infertility and spontaneous miscarriage. fertility affets aroud eret of te oulatio ad rougly to eret of all regaies i te ed i misarriage may ases te auses of ifertility ad misarriage are uow team led y lar a rofessor of moleular ell ad deelometal iology ad memer of te li ad dyte road eter of egeeratie ediie ad tem ell esear at set out to fid ow eigeomi ages ogeeti ifluees o gee eressio i uma emryoi stem ells ould elai wy some emryos are ot iale ey started y aalyig ells witi te early emryo tese ells are luriotet meaig tat tey a tur ito ay ell witi te uma ody or may years researers tougt tat uma luriotey was a sigle state lar said oweer oer te ast tree years te field as disoered tat uma luriotey ioles at least two maor states ad as emryos grow te stem ells ass troug tese two differet states of luriotey o te way to te emryo estalisig a regay fter a uma emryo is fertilied ad efore it imlats i te uterie liig ells i te emryo are i a ery immature state of luriotey alled te aie state ittle is ow aout te aie state ut sietists eliee tat if emryoi ells aot first eter tis state te emryo is ot iale ad a misarriage would our roud te time a emryo imlats its ells eter te rimed state rimed ells are ready to differetiate ito all of te arious ell tyes i te ody ltoug o oe ows eatly wy te aie state of luriotey eists or wat els aie ells stay i tat state for a eriod of time it ould e to roide a rotetie meaism tat reets te emryoi ells from differetiatig too uily wi would esure te timig of imlatatio is rigt lar said o etter uderstad wat els regulate te aie state te researers omared eigeomi ages i lareated aie ad rimed emryoi stem ells ey disoered tat ot ell tyes ae differet seuees of oe romati trougout teir romati osists of ad rotei tat odese to form te romosomes witi a ells uleus iue seuees of oe romati witi ay ell tye at as ar odes eeregulatig roteis alled trasritio fators i te oe areas of romati sa te ar ode ad te id to it wi ifluees geeti atiity i te ell e looed seifially at oe romati ad foud a ar ode tat is uiue to aie emryoi stem ells reeated oer ad oer agai so we ased wat trasritio fator reogies tat ar ode lar said e researers disoered tat a trasritio fator alled reogies te ar ode o lear more aout its seifi role tey deleted te gee tat maes te rotei from ot rimed ad aie emryoi stem ells i te laoratory usig a gee editig tool alled as | fertilityroadom | fertilityroadmag | follow us @fertilityroad
Sponsored by They found that the deletion had no effect on primed stem cells. Conversely, when TFAP2C was deleted from naive stem cells, the areas of open chromatin associated with the naive state closed and the naive stem cells passed into a primed state. The research also revealed about 1,500 regions of open chromatin that are very sensitive to the loss of TFAP2C and showed that there are hundreds of genes associated with early embryonic development in those areas. “We’ve discovered that the presence of TFAP2C marks an important difference between the naive and primed states of pluripotency, and that TFAP2C is necessary to maintain the naive state of pluripotency,” Clark said. “We also showed that without TFAP2C, hundreds of genes aren’t expressed correctly, which would most likely result in early miscarriage.” In addition, the researchers verified that the regions of open chromatin present in lab-created naive embryonic stem cells are also present in embryos before the stage associated with implantation. “Our findings are relevant to the natural process of human development because they match up with what we see in human pre-implantation embryos,” Clark said. “This provides new information about a time in the lifecycle that we know little about. Fundamental knowledge like this could help better predict infertility or embryo quality.” The study also could lead to important advances in an area of medicine that historically has been underfunded and underappreciated — in part because the subject of infertility is sometimes seen as taboo and because it doesn’t attract the attention of deadly diseases like cancer. “People who experience infertility and miscarriage may tell close friends or family, but too often, these issues are not discussed,” Clark said. “But infertility is a significant health concern. It deserves our attention, and we as a society need to be more open about it.” The pluripotent stem cell research was supported by the Jane Coffin Childs Memorial Fund for Medical Research, the Chinese Scholarship Council, the National Institute of Child Health and Human Development, Australia’s National Health and Medical Research Council, the Silvia and Charles Viertel Senior Medical Research Fellowships and the Howard Hughes Medical Institute. The human embryo research was funded by the UCLA Broad Stem Cell Research Center and its training program. | fertilityroadmag | follow us @fertilityroad fertilityroad.com | 07
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FR News & Views<br />
UCLA RESEARCH<br />
MAY EXPLAIN<br />
SOME CAUSES OF<br />
INFERTILITY AND<br />
MISCARRIAGE<br />
STUDY EXAMINES HOW EARLY EMBRYONIC<br />
DEVELOPMENT CAN GO AWRY<br />
A new study in the journal Nature Cell<br />
Biology has uncovered information about a<br />
key stage that human embryonic cells must<br />
pass through just before an embryo implants.<br />
The research, led by UCLA biologist Amander<br />
Clark, could help explain certain causes of<br />
infertility and spontaneous miscarriage.<br />
fertility affets aroud eret of te <br />
oulatio ad rougly to eret of<br />
all regaies i te ed i misarriage<br />
may ases te auses of ifertility ad<br />
misarriage are uow<br />
team led y lar a rofessor of<br />
moleular ell ad deelometal iology ad<br />
memer of te li ad dyte road eter of<br />
egeeratie ediie ad tem ell esear<br />
at set out to fid ow eigeomi<br />
ages ogeeti ifluees o gee<br />
eressio i uma emryoi stem ells<br />
ould elai wy some emryos are ot iale<br />
ey started y aalyig ells witi te early<br />
emryo tese ells are luriotet meaig<br />
tat tey a tur ito ay ell witi te<br />
uma ody<br />
or may years researers tougt tat<br />
uma luriotey was a sigle state lar<br />
said oweer oer te ast tree years te<br />
field as disoered tat uma luriotey<br />
ioles at least two maor states ad as<br />
emryos grow te stem ells ass troug tese<br />
two differet states of luriotey o te way<br />
to te emryo estalisig a regay<br />
fter a uma emryo is fertilied ad efore it<br />
imlats i te uterie liig ells i te emryo<br />
are i a ery immature state of luriotey alled<br />
te aie state ittle is ow aout te aie<br />
state ut sietists eliee tat if emryoi ells<br />
aot first eter tis state te emryo is ot iale<br />
ad a misarriage would our roud te time a<br />
emryo imlats its ells eter te rimed state<br />
rimed ells are ready to differetiate ito all of te<br />
arious ell tyes i te ody<br />
ltoug o oe ows eatly wy te aie<br />
state of luriotey eists or wat els aie<br />
ells stay i tat state for a eriod of time it<br />
ould e to roide a rotetie meaism<br />
tat reets te emryoi ells from<br />
differetiatig too uily wi would esure<br />
te timig of imlatatio is rigt lar said<br />
o etter uderstad wat els regulate te<br />
aie state te researers omared eigeomi<br />
ages i lareated aie ad rimed<br />
emryoi stem ells ey disoered tat<br />
ot ell tyes ae differet seuees of oe<br />
romati trougout teir romati<br />
osists of ad rotei tat odese to<br />
form te romosomes witi a ells uleus<br />
iue seuees of oe romati witi<br />
ay ell tye at as ar odes eeregulatig<br />
roteis alled trasritio fators i te oe<br />
areas of romati sa te ar ode ad te<br />
id to it wi ifluees geeti atiity i<br />
te ell<br />
e looed seifially at oe romati<br />
ad foud a ar ode tat is uiue to aie<br />
emryoi stem ells reeated oer ad oer<br />
agai so we ased wat trasritio fator<br />
reogies tat ar ode lar said<br />
e researers disoered tat a trasritio<br />
fator alled reogies te ar ode<br />
o lear more aout its seifi role tey<br />
deleted te gee tat maes te rotei<br />
from ot rimed ad aie emryoi stem<br />
ells i te laoratory usig a gee editig tool<br />
alled as<br />
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