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Reproductive Immunology

Reproductive Immunology

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Published by Ivan Bubanovic
INTERLEUKIN-10 IN PLACENTAL DEVELOPMENT
AND LPS TOLERANCE IN PREGNANCY:
LESSONS FROM NULL MUTANT MICE. Sarah A.
Robertson, Christine A. White, Claire T. Roberts,
Alistair J. Ramsay University of Adelaide Obstetrics
and Gynaecology, S.A. Medical School, Adelaide,
Australia.
Interleukin-10 (IL-10) is an anti-inflammatory and
immune-deviating cytokine expressed in the endometrium
and placenta. IL-10 is implicated in maternal
immune tolerance as well as regulation of trophoblast
invasion via inhibiting MMP-9 activity and NO
production. We have employed mice with a null
mutation in the IL-10 gene to analyse the physiological
significance of IL-10 in pregnancy. Immune and
inflammatory parameters, implantation success, placental
development and reproductive outcome were
examined in IL-10 null mutant C57B/66 (IL-10-/-) and
control (IL-10+/+) mice. Endometrial inflammation
was amplified early in pregnancy in IL-10-/- mice, with
a 70% increase in leukocytes in the endometrial stroma
at implantation. Despite this, no evidence of abnormal
type 1 / type 2 skewing was seen in T-lymphocytes
from draining lymph nodes. IL-10-/- females mated
with IL-10-/- males had similar or slightly increased
numbers of implantation sites compared with pregnant
wild-type (IL-10+/+) mice. Similar data were
obtained in allogeneic pregnancies. IL-10 deficiency
altered placental structure, with a 28% increase in the
cross sectional area of the placenta, principally due to
an enlarged labyrinth. The proportion of maternal
blood space in the labyrinth was increased by 26% and
trophoblast surface area was 41% larger. Fetuses
gestated in IL-10-/- mothers had an altered growth
trajectory, being approximately 10% larger late in
gestation and at birth, but with growth impairment
evident from early postnatal life into adulthood. In
addition, IL-10-/- mice were highly susceptible to
bacterial LPS, with higher rates of pregnancy failure
and fetal resorption induced after low dose LPS
injection on day 10 of pregnancy, accompanied by
dramatically increased levels of TNFalpha in serum,
uterine and conceptus tissues. This study shows that
IL-10 is not essential for maternal immune tolerance or
successful pregnancy irrespective of fetal MHC disparity.
However, maternal IL-10 deficiency is associated
with abnormal uterine inflammatory parameters
and decreased resistance to LPS challenge. In the
absence of IL-10, structural correlates of placental
INTERLEUKIN-10 IN PLACENTAL DEVELOPMENT
AND LPS TOLERANCE IN PREGNANCY:
LESSONS FROM NULL MUTANT MICE. Sarah A.
Robertson, Christine A. White, Claire T. Roberts,
Alistair J. Ramsay University of Adelaide Obstetrics
and Gynaecology, S.A. Medical School, Adelaide,
Australia.
Interleukin-10 (IL-10) is an anti-inflammatory and
immune-deviating cytokine expressed in the endometrium
and placenta. IL-10 is implicated in maternal
immune tolerance as well as regulation of trophoblast
invasion via inhibiting MMP-9 activity and NO
production. We have employed mice with a null
mutation in the IL-10 gene to analyse the physiological
significance of IL-10 in pregnancy. Immune and
inflammatory parameters, implantation success, placental
development and reproductive outcome were
examined in IL-10 null mutant C57B/66 (IL-10-/-) and
control (IL-10+/+) mice. Endometrial inflammation
was amplified early in pregnancy in IL-10-/- mice, with
a 70% increase in leukocytes in the endometrial stroma
at implantation. Despite this, no evidence of abnormal
type 1 / type 2 skewing was seen in T-lymphocytes
from draining lymph nodes. IL-10-/- females mated
with IL-10-/- males had similar or slightly increased
numbers of implantation sites compared with pregnant
wild-type (IL-10+/+) mice. Similar data were
obtained in allogeneic pregnancies. IL-10 deficiency
altered placental structure, with a 28% increase in the
cross sectional area of the placenta, principally due to
an enlarged labyrinth. The proportion of maternal
blood space in the labyrinth was increased by 26% and
trophoblast surface area was 41% larger. Fetuses
gestated in IL-10-/- mothers had an altered growth
trajectory, being approximately 10% larger late in
gestation and at birth, but with growth impairment
evident from early postnatal life into adulthood. In
addition, IL-10-/- mice were highly susceptible to
bacterial LPS, with higher rates of pregnancy failure
and fetal resorption induced after low dose LPS
injection on day 10 of pregnancy, accompanied by
dramatically increased levels of TNFalpha in serum,
uterine and conceptus tissues. This study shows that
IL-10 is not essential for maternal immune tolerance or
successful pregnancy irrespective of fetal MHC disparity.
However, maternal IL-10 deficiency is associated
with abnormal uterine inflammatory parameters
and decreased resistance to LPS challenge. In the
absence of IL-10, structural correlates of placental

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Published by: Ivan Bubanovic on May 24, 2009
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10/14/2012

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