(The) effects of cortisone acetate on the rat placenta
Glucocorticoids, such as cortisone have been known to be teratogenic in mice and
also induce reabsorption and abortion of the fetus in pregnant rabbits, rats, mice,
and guinea pigs(Domm and Leroy, 1951; Leroy and Domm, 1951; DeCosta and Abelman,
1952; Robson and Sharaf, 1952; Lee and Ring, 1956; Ingallis and Curley, 1957). But,
it is not known whether cortisone produces fetal malformation by direct action on
the embryo or through some action on the pregnant female (Kalter, 1965). However
the fact that fertility as well as uterine, placental, and fetal development is in
several ways dependent upon maternal adrenocorticoid hormone production is now well
documented (Amoroso, 1955). To date, only a few investigators have recorded
cortisone-induced morphological changes in the placentas of experimental animals.
The present study is an attempt to investigate the probable site of influence in
the placenta by cortisone, that could be related to fetal death, reabsorption,
using the light and electron microscopic examinations in albino rats.
Materials and Methods
Female albino rats weighing around 200 gms. were used for the experiment and
mated. The pregnant females were divided into two groups as follows.
Group Ⅰ: Normal control (35 pregnant rats)
Group Ⅱ: Cortisone treated (35 pregnant rats)
Each group was subdivided into seven groups. In the experimental group, daily
dose of 5 mg of cortisone acetate per animal was given intramuscularly. The
placentas were obtained on the 10th, 12th, 14th, 16th, 18th, 19th, and 20th day of
the pregnancy in both experimental and control groups. For histologic examination
the routine hematoxylin-eosin staining method was performed, and PAS staining
method for mucopolysaccharide and glycogen, methyl-green pyronin staining method
for RNA, and reticulum staining method for reticulum fiber was also applied. For
the electron microscopic examination the tissue was fixed in 1% osmium tetraoxide
in phosphate buffer of pH 7.4 for 2 hours, and embedded in Epon 812 after
dehydration. Sections were made with a glass knife of 400 to 500 A in thickness and
stained with uranyl acetate and lead hydroxide. Observations were made with Hitachi
HU 11-E model electron microscope.
The following results were made in observation of the placental changes of the
pregnant rats treated with cortisone acetate by the light and electron microscopy.
1) The wet placental weights of cortisone-treated groups were decreased in
comparison with that of the control group.
2) In cortisone-treated groups even though the morphologic changes of vitelline
membrane and junctional zone of the placenta were not much different from those of
the control group, the placental labyrinth showed early congestion and atrophy,
with early degenerative changes of trophoblasts.
3) The positive periodic acid Schiff stained material in the trophoblasts of the
rat placenta treated with cortisone was relatively decreased at the late
gestational period. Meanwhile the methyl-green pyronin reaction of trophoblasts in
those group showed decreased reaction of trophoblasts in early phase of placental
4) The dilatation of rough endoplasmic reticulum and detachment of ribosomes in
trophoblasts of early placental formation were found by electron microscopy.
On the basis of the above findings the cortisone induces marked congestion of
placental labyrinth, atrophy and degeneration of trophoblasts, decreased positive
meterial of PAS, and interference of protein synthesis in the rat placenta.
It is speculated that those changes might be related with the death, abortion and
reabsorption of the fetus.