Effects of an antioestrogen (mer 25) on sexual and

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Description

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.

Informations

• Publié par: julien23
• Nombre de lectures: 92
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

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