Maternal disturbance in activated sphingolipid metabolism causes pregnancy loss in mice
J. Clin. Invest. Kiyomi Mizugishi, et al. 117:2993 doi:10.1172/JCI30674 [
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Figure 4Decreased cell mitosis and increased cell death in
Sphk1–/–Sphk2+/– decidua.
(
A–
H) Immunostaining with anti-phospho-histone H3 on wild-type (
A,
B,
E, and
F) and
Sphk1–/–Sphk2+/– (
C,
D,
G, and
H) uteri on day 5.5 pc (
A–
D) and day 6.5 pc (
E–
H). (
I) Percentage of phospho-histone H3–positive cells.
n = 6 matched pairs. *
P < 0.05; **
P < 0.01, paired Student’s
t test. (
J and
K) TUNEL assay on wild-type (
J) and
Sphk1–/–Sphk2+/– (
K) uteri on day 5.5 pc. Arrows in
K indicate the increased cell death in
Sphk1–/–Sphk2+/– uteri. (
L–
O) TUNEL assay on wild-type (
L and
M) and
Sphk1–/–Sphk2+/– (
N and
O) uteri on day 7.5 pc.
M and
O represent high-power views of the boxed areas in
L and
N, respectively. Arrows in
N indicate the increased cell death in
Sphk1–/–Sphk2+/– decidua. (
P and
Q) Immunostaining with anti-cytokeratin to label trophoblast cells on day 7.5 pc
Sphk1–/–Sphk2+/– uteri.
Q represents a high-power view of the boxed area in
P. Arrows in
P correspond to those in
N. Note no positive staining in the area indicated by arrows. Arrowheads indicate positive trophoblast cells. (
R and
S) Immunostaining with anti-desmin to label decidual cells on day 7.5 pc
Sphk1–/–Sphk2+/– uteri.
S shows a high-power view of the boxed area in
R. Arrows in
R correspond to those in
N. Note shrunken decidual cells and normal decidual cells indicated by arrows and asterisks, respectively, in
S. Scale bars: 100 μm (
A–
H and
L–
S); 50 μm (
J and
K). In all experiments, more than 3 animals were examined.
