Effects of an antioestrogen (mer 25) on sexual and
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Effects of an on andsexualantioestrogen (MER-25) of mousethe fetusglandmammary morphogenesis M.Ch. M. de G. andJean-Faucher, Turckheim, Veyssi\l=e`\reBerger, Cl. Jean et Université de ClermontPhysiologie Comparée Endocrinologie, II, desComplexe B.P. 63170 FranceScientifique Cézeaux, 45, Aubière, The role of fetal in the sexual and differentiation of rodents has been investi-androgens mammary radio-destruction of the fetal testis andgated by methods, (see Raynaud, 1969) themany including administration of acetate & Neumann,antiandrogens, especially cyproterone (Elger 1966; Jost, Jean & have not been used in this ofJean,1972; Veyssi\l=e`\re, 1974). Antioestrogens, however, type and we have therefore determined the effects of an Terenius &study antioestrogen (MER-25: on the of the and of the mouse fetus.1972) anlagenLjungkvist, development genital mammary Swiss strain mice received subcutaneous of 5 : Merrellethamoxytriphetol (MER-25injections mg National from the 13th to the 18th of All fetuses were delivered onLaboratories)/day day gestation. fixed for19 Caesarean and examination. TheDay by section, weighed histological genital apparatus and the two of were studied from serial sections. The volume of thepairs inguinal mammary anlagen first was determined on camera lucida ofmeasurements all sections.pair by planimetrie drawings female and were studied and with andfetuses, 12 8 male, 10 male 10 femaleTwenty compared control fetuses of the same age.
Voir
Effects
of
an
antioestrogen
(MER-25)
on
sexual
and
mammary
gland
morphogenesis
of
the
mouse
fetus
Ch.
Jean-Faucher,
M.
Berger,
M.
de
Turckheim,
G.
Veyssi\l=e`\re
and
Cl.
Jean
Physiologie
Comparée
et
Endocrinologie,
Université
de
Clermont
II,
Complexe
Scientifique
des
Cézeaux,
B.P.
45,
63170
Aubière,
France
The
role
of
fetal
androgens
in
the
sexual
and
mammary
differentiation
of
rodents
has
been
investi-
gated
by
many
methods,
including
radio-destruction
of
the
fetal
testis
(see
Raynaud,
1969)
and
the
administration
of
antiandrogens,
especially
cyproterone
acetate
(Elger
&
Neumann,
1966;
Jost,
1972;
Veyssi\l=e`\re,
Jean
&
Jean,
1974).
Antioestrogens,
however,
have
not
been
used
in
this
type
of
study
and
we
have
therefore
determined
the
effects
of
an
antioestrogen
(MER-25:
Terenius
&
Ljungkvist,
1972)
on
the
development
of
the
genital
and
mammary
anlagen
of
the
mouse
fetus.
Swiss
strain
mice
received
subcutaneous
injections
of
5
mg
ethamoxytriphetol
(MER-25
:
Merrell
National
Laboratories)/day
from
the
13th
to
the
18th
day
of
gestation.
All
fetuses
were
delivered
on
Day
19
by
Caesarean
section,
weighed
and
fixed
for
histological
examination.
The
genital
apparatus
and
the
two
pairs
of
inguinal
mammary
anlagen
were
studied
from
serial
sections.
The
volume
of
the
first
pair
was
determined
by
planimetrie
measurements
on
camera
lucida
drawings
of
all
sections.
Twenty
fetuses,
12
female
and
8
male,
were
studied
and
compared
with
10
male
and
10
female
control
fetuses
of
the
same
age.
The
body
weight
of
control
fetuses
was
not
significantly
different
from
that
of
the
experimental
fetuses
(1104
±
39
(S.E.M.)
mg
and
1097
±
28
mg
respectively)
and
MER-25
clearly
does
not
modify
body
growth.
The
antioestrogen
did,
however,
modify
the
morphology
and
the
volume
of
the
mam¬
mary
gland
anlagen
of
females.
In
the
control
females,
an
anläge
was
composed
of
a
mam¬
mary
cord
attached
to
the
epidermis
and
surrounded
by
an
annular
epidermal
invagination
which
marks
the
limit
of
the
future
nipple
(PL
1,
Fig.
1).
The
differentiation
of
the
nipple
was
completely
inhibited
by
MER-25
(PL
1,
Fig.
2),
leading
to
a
generalized
athelia
which
affected
all
48
rudiments
studied.
In
spite
of
the
appearance
shown
in
PL
1,
Figs
1
and
2
there
was
no
particular
development
of
the
mesenchyme
adjacent
to
the
primary
cord.
The
volume
of
the
first
inguinal
mammary
cord
was
inhibited
in
the
fetuses
of
treated
females,
being
30-7
±
2-2
10-4
mm3
in
control
fetuses
and
23·9
±
1-3
10~*
mm3
in
experimental
fetuses.
This
difference
of
22-1
%
is
statistically
significant
(0001
< <001,
Student's
ttest).
Sexual
differentiation
was
apparently
not
affected
except
for
the
abnormal
development
of
prostatic
rudiments
in
females.
These
formations
were
absent
in
control
females
(PL
1,
Fig.
3),
whereas
they
were
present
in
8
out
of
12
experimental
females.
These
anlagen,
which
are
composed
of
2
to
3
buds
on
the
ventral
uterine
wall
(PL
1,
Fig.
4),
are
much
less
developed
than
in
males
of
the
same
age.
To
try
and
explain
these
masculinizing
effects
of
MER-25,
we
investigated
its
possible
androgenic
effects.
Twenty
adult
male
mice
were
bilaterally
castrated.
On
the
day
after
the
operation,
10
mice
were
treated
with
5
mg
MER-25/day
for
6
days,
and
the
other
10
mice
served
as
controls.
All
the
animals
were
killed
24
h
after
the
last
injection.
No
significant
difference
was
found
in
the
weight
of
the
seminal
vesicles
of
the
two
groups
of
animals.
MER-25
failed
to
prevent
the
atrophy
of
seminal
vesicles
which
follows
castration
and
therefore
has
no
apparent
androgenic
action
under
the
experi¬
mental
conditions
utilized.
The
development
of
prostatic
buds
in
females
treated
with
MER-25
does
not
seem
to
be
due
to
a
direct
androgenic
effect
of
this
compound
and
remains
difficult
to
explain.
Neither
the
genital
apparatus
nor
the
mammary
glands
are
modified
in
male
fetuses
treated
with
MER-25.
Our
results
show
that
MER-25
suppresses
nipple
differentiation
and
significantly
reduces
the
