The defect of mili mutant in the self-renewal of spermatogonial
stem cells. A-D, testicular sections of 5-day-old (A and
B) and 8-day-old (C and D)
mili+/- (A and C) and
mili-/- (B and D) mice stained with EE2
antibody to outline spermatogonia (red), anti-phosphohistone 3
antibody to label mitotic cells (green), and DAPI to label DNA
(blue). The mili+/- and
mili-/- testes contain the same number of spermatogonia,
as quantified in M, but the mitotic rate in the
mili-/- (2.1 ± 0.4%) is noticeably lower than that
of mili+/- spermatogonia (3.6 ± 0.4%). Note that
all spermatogonia (Sg) at 5 dpp are germ line stem cells.
Gc, gonocyte; mGc, mitotic gonocyte; SSC,
spermatogonial stem cell; mSSc, mitotic SSC; mLd, mitotic
Leydig cells. E-H, hematoxylin/eosin-stained testicular sections of
10-day (E and F) and 35-day (G and H) old
mili+/- (E and G) and
mili-/- (F and H) mice. Sc,
spermatocyte; Sd, spermatid; Sp, sperm. In
mili-/- testes, most germ cells are arrested as
spermatogonia, with a tiny fraction of germ cells differentiating into
spermatocytes. However, no spermatid is detected. This phenotype persists
through up to 180 days and was qualified at 98 days in N. I and
J, testicular sections of 98-day-old mili+/-
(I) and mili-/- (J) mice stained for EE2
(red), phosphohistone 3 (green), and DNA (blue).
The mitotic rate of mili-/- spermatogonia is significantly
lower than that of the mili+/- spermatogonia, as
quantified in O. mSg, mitotic spermatogonia. K and
L, testicular sections of 98-day old mili+/-
(K) and mili-/- (L) mice stained with
BC7 antibody to mark spermatocytes (green) and terminal
deoxynucleotidyltransferase-mediated dUTP nick end labeling to mark apoptotic
cells (ac; red) and DNA (blue). Stc,
Sertoli cell. Note that drastic apoptosis occurs in the arrested
mili-/- germ cells. Bars in A, I, and
K denote 50 μm for A-H, I and J, and K
and L, respectively. M-O, quantitative comparisons between
mili+/- and mili-/- testes with regard
to the number of spermatogonia per tubule at 5 dpp (M) and 98 dpp
(N), and mitotic index of spermatogenic cells at 8 dpp (M)
and 98 dpp (O).