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The healing of wounds of the uterus of the mouse.

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THE HEALING O F WOUNDS O F THE U T E R U S O F
THE MOUSE1
CHARLES WRIGHT HOOKER
Uepartmciit of A i m t o s l y , Pale University School of Medicine, Xew Haoen,
Connecticut
T W O PLAl'ES (TWELVE FIQURES)
Although there has accumulated a vast literature dealing
with problems of the healing of wounds, most of the studies
have dealt with skin wounds. The repair of wounds of hollow
viscera, especially cylindrical organs, has by comparison received scant attention, notwithstanding the number of interesting questions wliich arise concerning the mechanism by which
a longitudinal slit in a cylindrical viscus heals, especially if
no artificial means a r e employed to approximate the cut edges
of the wound.
By virtue of its accessibility for operation and its resistance
to infections a c o r m of the rodent uterus is a very favorable
organ for such a study. Moreover, a reasonably rapid repair
of the uterus following wounds of the type under consideration
has been reported by Selye and RIcKeown ('34) for the r a t
and mouse. The dependence of uterine morphology upon the
ovary serves to multiply the interesting features of the problem
since the effect which might be produced by sex hormones upon the healing of the uterus is quite unpredictable.
This study was aided by a grant from the Fluid Research Fund of Pale Univcrsity School of Medicine. The mice were obtained through the kindness of Dr. L. C.
Strong from his colony. The hormone preparations, estradiol benzoate, progesterone, and testosterone propionate, were supplied by the Schering Corporation
through the courtesy of Dr. E. Schwenk.
211
212
CHARLES WRIGHT HOOKEEt
For example, the growth-stimulating action of estrogen upon
the uterus inight be expected to promote healing, although the
growth, occurring as it does primarily in the endometrium,
might just a s reasonably be expected to oppose approximation
of the cut surfaces. Similarly, the increased motility of the
uterus and the increase in secretion which result from estrogen
might antagonize repair. The effects of other sex hormones
are equally unpredictable.
For the present study the mouse uterus was selected. The
healing process in the absence of sex hormone influences was
studied in ovariectomized animals. The effect of sex hormones
was examined in ovariectomized animals receiving injections
of various hormone substances. Certain of tlie findings have
already been described in preliminary form (Hooker, '38).
While these observations were being extended Jett-Jackson
('39) reported the results of a somewhat similar study in the
rat.
METHODS
A total of 107 adult mice of several highly inbred strains
and hybrids of various ages has been used. Except where
otherwise noted all the mice were ovariectomized, and 10 days
to 2 weeks later the left horn of the uterus was slit longitudinally throughout its entire length. 111 me.king the wound
the uterus was suspended by a large curved needle inserted
through the mesometrium and, to minimize trauma, the uterus
itself was touched only by the scissors with which the wound
was made. The uterus ordinarily fell open into a more or less
ribbon-like structure. When this did not occur the curved
organ was gently flattened with a small, curved forceps before
closing the abdomen. No sutures or other means were employed t o close the uterine wound. At autopsy the entire
uterus was fixed, and the injured horn was usually studied in
serial sections. The sections were stained routinely with
Ehrlich 's hernatoxylin and eosin, although occasionally
Mallory 's connective tissue stain and Foote's modification
of the Bielschomsky stain were used.
WOUND HEALING IN MOUSE UTERUS
213
RESULTS
The ?intreated ovariectonaized animal
Twenty-six animals were subjected t o the wounding operation and were killed a t intervals of 1day for 12 days after the
injury. I n many instances healing was complete after the
remarkably short period of 48 hours, while in other cases
6 to 8 days were required. As might be expected, all the
regions of a uterus were not a s a rule repaired simultaneously.
Often by study of serial sections all the phases of the repair
process could be seen in a single uterine horn; one end of
the cornu might be open flat and the other end completely
healed, with the mid-portion presenting a gradation of all the
intermediate phases of repair.
The earliest event leading to repair of the flattened uterus
was healing of the two cut surfaces. This process was the
classic type of healing involving fibroplasia, liyalinization, and
contraction of the wound in such a way as t o pull the endometrial and serosal surfaces of the flattened uterus toward
each other, followed by migration of both the endometrial and
serosal epithelia to meet over the bare area (fig. 1). If the
epithelial covering developed before the cut surface established
contact with the fat, no adhesions formed irrespective of the
quantity of inguinal fat which the animal possessed.
While the slit uterus was still open flat the circular muscle
layer became thinner in the mesometrial portion and increased
in thickness near the cut (fig. 1).The ends of this muscle layer
came t o be directed toward the longitudinal muscle layer, and
they attached either to this layer or to the “scar” immediately adjacent. That there was any extensive proliferative
activity in the circular muscle layer to aid in the establishment
of the arrangement described seems rather doubtful. At any
rate, few mitoses in these muscle cells have been seen even
in animals which had received colchicine following the use of
which Allen, Smith and Gardner (’37) have seen mitoses in
the myometrium of estrogen-treated mice.
214
CHARLES WRIGHT HOOKER
The arrangement of the circular muscle layer in the flattened
uterus seems to be such that if this layer were to contract,
the cut edges of the uterus would be rolled i n a n antimesometrial direction. Further contraction of the circular muscle
layer would roll the cut edges upward until ultimately they
would be approximated. Whether or not this mechanism was
actually operating, the tubular form of the uterus was regained by a rolling process as shown in figures 2 and 3. I n
all phases of formation of the tube the muscle arrangement
described for the flattened uterus persisted (figs. 1 to 5 ) ,
and this arrangement was lost only after the uterus had again
become a tube. I n this connection it is significant that the last
portion of the uterus to heal was the transverse nick made in
the uterus in order to insert a scissors for the longitudinal slit.
After the flattened uterus had rolled into a tube with the
cut edges approximated, the epithelium over the cut surfaces
degenerated. The process of approximation was such that it
sometimes happened that squamous epithelium of the serosa
was caught within the uterus to form a p a r t of the epithelial
lining, or that columnar epithelium of the endometrium covered
a portion of the periphery. The remainder of repair process
consisted chiefly of migration. The longitudinal muscle layer
was already complete and merely re-aligned itself. The circular muscle layer migrated across the gap, thc tunica propria
fused (fig.5),and the wound was healed (fig. 6). The establishment of a continuous circular muscle layer was the result of
muscle cell proliferation a s well a s the product of muscle cell
migration a s indicated by the presence of mitoses in the region
of fusion. In this healing there was no indication of scar
formation, and it was impossible by examination of sections
of the healed uterus to locate the site of the previous wound
(fig. 6). Muscle damaged in these uteri was replaced by muscle
and not by connective tissue.
The description just given applies only to unimpeded liealing. I n animals possessing a large amount of inguinal fat the
uteri exhibited a decided retardation in healing due either
to the formation of adhesions to the f a t or to mechanical block-
WOUND HEALING I N MOUSE UTERUS
215
ing of the approaching wings of the uterus. If fat pressed
against the cut surface of the uterus before its epithelial
covering appeared, quite firm adhesions formed. The adhesions consisted of invasion of the fat by cells of the tunica
propria and growth of the serosal and endometrial epithelia
over the f a t (fig. 7). In the presence of adhesions of this
character approximation of the cut edges solely by a rolling
of the uterus was, of course, difficult or impossible. Accordingly, the tunica propria became greatly thickened in the
portion near the wound, and its extensions upon the fat closed
the operated uterus. The myometrium was not united and its
gap was filled by the union of these extensions of tunica
propria. The endometrial epithelium of each uterine wing
grew onto the fat with the tunica propria. These epithelial
extensions met and fused with the result that there was
established a uterine lumen lined by epithelium. The uterus
was now entirely healed except for absence of myometrium in
tlie wound area and an attachment of this area to f a t (fig. 8).
If the fat came to lie in the path of the approaching cut edges
of the uterus, the effect was a mechanical blocking as shown
in figure 9. The f a t sometimes entirely prevented approximation of the cut edges, or it was sonietimes merely captured
by the rolling uterus and was, in time, pierced sufficiently
to allow complete healing. Although there were no adhesions
in the specimens showing merely mechanical blocking, the
effect upon the curving uterus was the same in that such blocking opposed the rolling action of the circular muscle layer.
The tunica propria thickened in the vicinity of the cut edges ;
but the thickenings did not approach each other sufficiently
in any of the cases to effect fusion. None of these wounds
completely healed. The endometrial epithelium usually
branched, with one branch covering tlie cut surface and other
branch growing over the fat. Upon the fusion of the “ f a t ”
branches of the epithelium there was established a lumen lined
by epithelium and surrounded i n part by the curved uterus
and in part by f a t between the cut edges.
216
CHARLES WRIGHT HOOKER
From the above observations it seems clear that the uterus
of the mouse heals in either of two ways. What may be termed
the normal process consists of approximation of the cut edges
by rolling followed by migration and fusion of the various
coats of the uterus, without the formation of a scar. I n the
former instance fibroplasia plays an insignificant part in the
healing, while in the latter fibroplasia is the essential phase
a s in the healing of other organs. It was of interest, therefore,
to determine whether artificial stimulation of fibroplasia would
alter the mode of healing. Various substances, among them
urea and allantoin (Robinson, ' 3 5 ) , have the capacity of
inducing marked fibroplasia and have been used to accelerate
the healing of skin wounds. Allantoin was chosen f o r the
present purpose.
When the wound was made crystals of allantoin were placed
in the open, flattened uterus of five mice. A t examination 2
and 3 days later the uteri were quite hyperaemic and the tunica
propria was somewhat edematous. The entire uterus was in a
state of active proliferation a s shown by the relatively large
number of mitoses in all the coats, especially the tunica propria
which was greatly thickened. The endometrial epithelium was
much higher than that of a spayed animal and the glands
were moderately developed. I n respect to the hdema, the
glands, and the height of the epithelium these uteri were remarkably similar t o uteri of mice after small amounts of
estrogen. This condition was less apparent after 3 or 4
days, doubtless associated with the elimination of the
allantoin.
Healing of the allantoin-treated uteri was considerably
retarded due t o a change in type of healing. As a result
of its thickening the tunica propria protruded to such an
extent that it lay between the approaching wings of the
myometrium (fig. 10) and prevented their approximation.
The consequence was healing by scar which replaced the
myometrium in the region of the wound (fig. 11). Even when
no adhesions formed and in the absence of blocking by fat,
the allantoin-treated uteri healed in essentially the manner of
WOUND HEALING I N MOUSE UTERUS
217
an untreated uterus whose rolling has been impeded. Adhesions
formed by the allantoin-treated uteri were much heavier than
adhesions in untreated animals and sometimes even everted
the uterus. These adhesions were extremely cellular and characterized by great numbers of mitoses and by the development of many fibers. The adhesions leave no doubt that the
treatment stimulated fibroplasia. I n certain peripheral regions
these growths u7ere remarkably similar to pure in vitro cultures
of fibroblasts.
E f e c t s of estrogem
To test the effects of estrogen forty-seven mice were employed and two procedures were followed. One group of mice
received injections of 500 I.U. of estradiol benzoate at intervals of 48 hours, and the wound was made approximately
24 hours after the first injection. Another group received the
same treatment, with the exception that the first injection
was made at the time of the uterine operation. The difference
in the two procedures lies in the fact that the most rapid
growth of the uterus occurred prior to wounding in the first
group, whereas in the second group the most rapid uterine
growth occurred subsequent to the operation. At daily intervals animals from each group were killed for study.
The estrogen treatment was entirely devoid of any cletectable effect upon either the rate or method of repair of the
wound, despite an obviously greater irritability and a much
greater thickness of the endometrium in the estrogen-treated
mice. The thickening of the tunica propria, although marked,
was uniform and, contrary to the condition in the allantointreated animals, this layer never protruded through the gap
between the approaching wings of the myometrium except in
a few cases showing very firm adhesions. The endometrial
edema was uniform throughout the unoperated horn, while
the injured cornu presented variations according to the degree
of repair in the various portions. I n the open portion of the
horn the edema was marked but was mucli reduced in the
218
CHARLES WRIGHT HOOKER
closed portion, and the transition i n the degree of edema
corresponded fairly sharply with transition from the open
to the closed region of the uterus. The character of the adhesions in the animals receiving estrogen was the same as in
cast rat e s.
E f e c t s o f progesterone
Eight animals were given daily injections of 0.5 I.U. of
progesterone beginning at operation upon the uterus. Two
animals were killed f o r study on each of the first, second,
third and fourth days. I n all of the members of this group
the uteri exhibited the characteristic histologic reactions to
progesterone (Hooker, '40). The tunica propria of these uteri
was much thickened and hyperplastic, especially in the superficial portion, with only occasionally a slight edema in regions.
I n the animals autopsied 3 and 4 days after operation large
deciduomata had developed.
Healing of these uteri was retarded as shown by their open
character on the second, third and fourth days when similarly
uiiinterfered uteri of untreated castrates a r e almost or entirely
healed. As a result of its thickening the tunica propria bulged
considerably through tlie space between the cut edges of the
myometrium, sufficient in most places to prevent approsimation of the muscle layers with consequent reversion of the
healing to the type pui-sued by a uterus with adhesions or
after allantoin. This effect was, of course, intensified in the
uteri developing deciduomata.
E f e c t s of estrogen plus progesterone
Only two animals were used to test the effects of the simnltaneous action of both ovarian hormones. Beginning at the
wounding operation both animals were given 0.5 I.U. of
progesterone daily and 100 I.U. of estradiol benzoate every
48 hours. One animal was killed 2 days and the other animal
3 days after operation.
WOUND HEALING I N MOUSE UTERUS
219
These uteri showed the histology characteristically elicited
by the simultaneous action of estrogen and progesterone
(Hooker, '40). A small deciduoma formed in one uterus.
No effect upon the rate or mode of healing could be detected,
the uteri healing in a manner identical with the repair of the
uterus of the untreated mouse or of the mouse receiving
estrogen alone. It is interesting that, in the ratio used, the
estrogen apparently neutralized completely the retarding influence of progesterone.
E f e c t s of a n d r o g m
Five mice were given 250 y of testosterone propionate daily
beginning at operation, and on each of 5 days thereafter an
animal was killed f o r study. All of the uteri showed appreciable hyperaemia and slight but significant growth. There
was induced a slight and inconstant edema but, in general,
there was no significant or characteristic histologic response to
the androgen. No effect was seen upon either the mode o r rate
of healing.
Pregi.zancy
Since, of the hormones examined, only progesterone exerted
any detectable influence on the healing of the uterus, it was desirable to study the process under the influence of endogenous
progesterone as, for example, during pregnancy. To this end
one cornu of the uterus of eleven mice on the eighth to the
eighteenth day of pregnancy was slit throughout its length.
A t the uterine operation the embryos or fetuses and amnia
were removed from the operated horn i n all cases, and in a
few animals the placentae were also removed. Eleven, 13 and
16 days after operation the animals were killed for study.
The ovaries were, of course, left intact in these animals. When
the placentae were left intact they pressed against each other
to form a large mass in the cervical third of the cornu. This
mass offered a decided obstacle to healing and, t o avoid studying merely mechanical influences, only the ovarian half of the
horn was sectioned. The entire cornu was sectioned if the
placentae had been removed when the uterus was slit.
220
CHARLES WRIGHT HOOKER
I n two instances (both 16 days after operation) the healing
of the ovarian end of the horn was complete and presented
little or no evidence of scar. The remaining nine uteri were
in various stages of repair by a process in which fibroplasia
was playing quite a significant part, with the mode of healing
and the uterine histology essentially tlie same as in spayed
animals receiving progesterone. The sections gave the impression that the rolling action of the uterus had not been a t all
vigorously pursued. I n any event, it is clear that healing was
greatly retarded in a t least nine of eleven mice in different
stages of pregnancy.
Lactatioii
I n three lactating mice 3, 7 and 10 days post-partum one
horn of the uterus was slit throughout its length. The animals
were killed for study 5, 6 and 13 days later respectively. The
ovaries were left intact in these animals.
Uterine repair was quite evidently retarded as shown by the
fact that none of them was entirely healed. Histologically
these uteri were very similar t o those of the animals receiving
progesterone. A small deciduoma was present in the animal
operated on the third day of lactation and killed 5 days later.
The healing process appeared to consist primarily of fibroplasia with rolling and migration constituting a less significant
phase, recalling the repair in progesterone-treated animals.
DISCUSSION
The type of healing exhibited by the mouse's uterus in the
absence of interference by fat has not, it seems, been described
previously. I n the classical picture of wound healing (Arey,
'36; Boyd, '38; McCallum, '36) the defect is filled by a clot
which is later organized by capillaries and fibroblasts. This
bridge of scar tissue contracts drawing the wound edges together and is later replaced to a greater o r less degree by the
normal tissue components of the injured organ or region.
In the mouse's uterus the preliminary stages are completely
superseded by early approximation of the two cut surfaces
WOUND HEALING IN MOUSE UTERUS
221
through the rolling action of the circular muscle layer. Thus
it is not altogether surprising that the wound heals with such
rapidity and with no indication of scar formation.
The myometrium is probably of greatest significance in the
repair process and presents several points of interest, not the
least of which is the fact that, depending upon the point of
its insertion, the circular layer first draws the uterus open
and subsequently rolls it again into a tube. In the terminal
phases of repair muscle proliferation and migration result
in damaged muscle being replaced by muscle and not by connective tissue. Complete repair of injuries to smooth muscle
without the intervention of scar tissue has often been observed
(Walsh and Loeb, '17; Berry, '19; M'Intyrc, ' 2 5 ) . Whether
the muscle migration in the terminal stage of healing involves
mature muscle cells or myoblasts cannot be determined in the
material studied. I n its migration the muscle carried its feltwork of reticular fibers, and in all histologic respects the
completely healed uterus was indistinguishable from an unoperated uterus. I t is probable, therefore, that the full tensile
strength (Harvey and Howes, '30) was soon regained, although this point was not tested.
It is quite probable that failure t o observe this type of
healing in cylindrical viscera has been due to the virtually
invariable practice of suturing wounds in such organs. The
sutures have doubtless induced sufficient foreign body reaction
to simulate cicatrization and thus possibly obscure a fundamental repair process similar t o that of the mouse uterus.
Apparently the ability of cylindrical viscera to heal unsutured
wounds has been tested only in the uterus of the mouse and
rat (Selye and McKeown, '34; Jett-Jackson, '39) and the
dog (Lentz, '29). The mode of healing has been discussed by
only Selye and McKeown who report, in marked contrast t o
the present findings, that the process is essentially fibroplasia.
These authors do not state whether the healing of their wounds
was accompanied by adhesions or mechanical blocking.
Any condition, such as adhesions o r mechanical blocking,
which significantly opposes the rolling action of the circular
222
CHARLES WEIGHT H O O K E R
muscle layer would in so doing retard approximation of the two
cut edges of the wound by the means normal for this cylindrical
viscus. When the extremely rapid apposition characteristic
of the uterus is incapacitated the means utilized by skin
wounds, i.e., fibroblastic activity, has the opportunity to manifest itself. The consequence is, of course, formation of scar
and greatly retarded healing of the wound. Direct stimulation
of fibroplasia with allantoin had essentially the same effect
upon the mode of repair. The similarity of the effects of
allantoin to the effects of small amounts of estrogen with
respect to the edema, glands and epithelium was doubtless the
result of the hyperaemia induced i n the uterus (Hechter, Lev
and Soskin, '40) rather than to any specific estrogenic property
of the allantoin. I n all groups the proportion of uteri showing
adhesions was unfortunately quite high due to presence of
fat adjacent to the mesometrium. It is quite impossible to
return the operated uterus to the abdominal cavity without
occasionally rolling the mesometrium and f a t about it. Such
a relation is impressed upon the uterus before the growth of
epithelium over the cut surface has even begun. The conditions a r e thus unavoidably optimal for the development of
adhesions.
The absence of acceleration o r retardation of healing by
estrogen is i n agreement with the findings of Jett-Jackson
('39) on the rat's uterus following much smaller amounts of
estrogen. The increase in uterine motility by estrogen
(Reynolds, '37) might be expected to accelerate healing: i n view
of the role of muscle in the process, although the great rapidity
of repair in the spayed animal virtually precludes acceleration. The marked diminution in the edema of the closed portion
as compared with the open portion of a healing uterus is
somewhat suggestive of compressibility of the edematous
uterus, a possible explanation of the inefficacy of this type of
thickened endometrium i n opposing closure of the slit uterus.
None of the animals used in this study developed endometrial
moles which have appeared in rats after various hormone
treatments following trauma (Selyc and Friedman, '40).
WOUND HEALING IN MOUSE UTERUS
223
The retardation of repair in animals receiving progesterone
contrasts with the absence of effect reported by Jett-Jackson
( '39), although the use of larger amounts of the hormone in
the present study doubtless explains the discrepancy. The
retarding effect of the progesterone was probably mediated in
two ways. One factor was the inhibition of uterine muscle
by the progesterone, involving the circular layer (in this
instance the significant layer) as well a s the longitudinal layer
(Robson, '35). Depression of the circular muscle would i n
itself be adequate to retard repair since contraction of this
layer is normally the means of approximating the two cut
edges. A second factor was the stimulation of fibroplasia in
the tunica propria which resulted in the development of a
much thickened, comparatively solid endometrium not apparently susceptible of compression, and by its structure
predisposing to the formation of scar. The effect on the tunica
propria was similar to, but hardly as marked as, the effects
of allantoin. The 11istol0,gy and mode of healing of the uteri
of the pregnant and lactating animals were like those of the
spayed animals receiving progesterone. The greater retardation of their repair indicates of tbat endogenous progesterone
is more effective in this regard than injected progesterone in
the amounts administered. The formation of deciduomata in
certain of the progesterone-treated animals served to exaggerate the thickening of the tunica propria and to be a further
retarding influence upon repair. I n castrated animals the
decidual reaction has been elicited previously only in rats
(Selye, '40) given progesterone alone (15 mg. daily) without
previous or concomitant treatment with estrogen.
Although testosterone propionate inhibits contractions of
the rabbit's uterus (Robson, '37; Leonard, Sager, and Hamilton, '37), the amount used in the present study apparently did
not inhibit the circular muscle sufficiently to retard healing,
nor were there morphologic effects of such character as to
modify the type of repair.
Whether the general type of healing exliiloited by the uterus
of the mouse would also occur in other cylindrical viscera
224
CHARLES WBIGHT HOOKER
cannot, of course, be predicted without actual testing. There
is no outstanding reason to suspect, however, that viscera
possessing the same general morphology and muscle arraiigement would not heal in a very similar manner under the same
conditions. The hormonal factors might, of course, be different
or non-existent.
SUMMARY
The healing; of a longitudinal slit in the uterus has been
studied in 10’7 mice. To control and analyze sex hormone
influences the repair process was first examined in ovariectomized animals. When the uterus was slit it drew open
into a flattened structure. The two cut edges of the flattened
uterus healed in the classical fashion completed by the union
of extensions of both the endometrial and serosal epithelia. The
circular muscle layer thinned in the region of the mesometrium
and thickened laterally. By a rolling process, apparently
accomplished by action of the circular muscle, the two cut
edges were approximated, thus restoring the tubular form of
the uterus. The remainder of the healing consisted of migration which established continuity of the various uterine tunics.
The fusion of the two wings of the uterus was entirely unaccompanied by scar formation. Complete healing was frequently accomplished within 48 hours.
I n the presence of adhesions to the f a t or of blocking by
the f a t the rolling of the uterus was impeded with the result
that the wound healed by scar formation. Stimulation of
fibroplasia with allantoin also changed the mode of healing
by inducing cicatrization of the wound preceded by marked
thickening of the tunica propria.
Injections of estrogen or androgen had no effect upon the
rate or mode of healing. Progesterone, however, induced healing by scar and retarded repair. This effect was mediated by
the stimulation of proliferation in the tunica propria and,
presumably, by inhibition of contractions of the circular
muscle. Administration of estrogen along with the pro-
WOUND HEALING IN MOUSE UTERUS
225
gesterone abolished the retarding and modifying influence of
the latter.
I n pregnant or lactating mice with intact ovaries healing
was markedly retarded, and the repair process was essentially
that followed by the uteri of the ovariectomized animals
receiving progesterone.
LITERATURE CITED
ALLEN, E., G . h!f. SMITH AND W. U. GARDNER 1937 Accentuation of the growth
effect of theeliu on genital tissues of the ovariectoniized mouse by
arrest of mitosis with eolchicine. Am. J. Anat., vol. 61, pp. 321-341.
AREY,L. B. 1936 Wound healing. Physiol. Rev., vol. 16, pp. 327-406.
BERRY,F. 1920 The regeneration of smooth muscle cells. J. Med. Research.
v01. 41, pp. 365-371.
BOYD,W. 1938 A textbook of pathology. Philadelphia.
HARVEY,
S. C., AND E. L. HOWES 1930 Effect of high protein diet on the
velocity of growth of fibroblasts in the healing wound. Ann. Surg.,
V O ~ . 91, pp. 641-650.
HECHTER,
O., M. LEV AND S. SOSKIN 1940 The relation of hyperemia t o the
action of estrin. Endocrinology, vol. 26, pp. 73-79.
HOOKER,
C. W. 3938 The healing of uterine wounds i n the mouse, with observations on the effect of estrogen. Anat. Rec., vol. 70 (suppl. no. 3 ) ,
p. 38.
1940 Effects of progesterone upon the uterus of the mouse. Proc.
Soc. Exp. Biol. and Med., vol. 45, pp. 270-272.
JEWJACKSON,
C. E. 1939 A study of the hormonal factor in the repair of
uterine tissue in the albino rat. Anat. Rec., vol. 74, pp. 79-89.
LENTZ,W. J. 1929 Case report: Caesarean section. Univ. of Pennsylvania
Bulletin, Veterinary Extension Quarterly, vol. 29, p. 3.
LEONARD,
S. L., V. SAGER
AND J. B. HAMILTON1937 Effect of male hormone
upon uterine motility and the uterus. Proc. Soe. Exp. Biol. and Med.,
VOI. 37, pp. 362-365.
MACCALLUN,
W. G. 1926 A textbook of pathology. Philadelphia.
M’INTYRE,
D. 1923 The healing of a uterine wound: Mitosis in unstriped muscle.
J. Path. and Bact., vol. 26, pp. 471-473.
REYNOLDS,
S. M. R. 1937 The nature of uterine contractility. Physiol. Rev.,
v01. 17, pp. 304-334.
ROBINSON,
W. 1935 Stimulation of healing in non-healing wounds by allantoin
occurring in maggot secretions and of wide biological distribution.
J. Bone a n d Joint Snrg., vol. 17, pp. 267-271.
ROBSON,J. M. 1935 The action of ovarian hormones on the uterine muscle
measured in vivo and in vitro. J. Physiol., vol. 85, pp. 145-158.
1937 Reactions of the uterine muscle and endometrium of the
rabbit t o testosterone. Quart. J. Exp. Physiol., vol. 26, pp. 355-359.
226
CHARLES WRIGHT HOOKER
SELYE,H.
1940 A’ctivity of progesterone in spayed females not pretreated with
estrin. Proc. SOC.Exp. Biol. and Med., vol. 43, pp. 343-344.
SELYE,H., AND S. FRIEDYAN
1940 On the production of endometrial moles with
steroid hormones. Am. J. Cancer, vol. 38, pp. 558-563.
SELYE,
H., AND T. M C K E ~ W N1934 On the regenerative power of the uterus.
J. Anat., vol. 69, pp. 79-81.
WALSH,L., AND L. LOEB 1918 A quantitative study of regeneration in the Uterus
of the guinea pig. J. &led. Research, vol. 37, pp. 441-470.
PLATE 1
EXPLANATION OF FIGURES
1 Open, flattened portion of a uterus 24 hours subsequent to slitting. The
two cut edges hare healed and are covered by epithelium. The circular muscle
layer has tliickencd a t the two extremities where it attaches primarily t o the
longitudinal muscle. Transverse section. X 20.
2 Rolled portion of a uterus 24 hours after slitting. Except for the curvature,
the relations are the same as in figure 1. Transverse section. X 20.
3 Section of a uterus with the cut edges approximated. Transverse section.
x 20.
4 The same, X 150, showing persistence of the inusrle relations of the flattened
uterus.
5 The rolling is conipleted and the migration phase has appeared. A lumen
lined by epithelium has formed. Fusion of the tunica propria is in progress.
Migration of the circular muscle layer across tlic interval has started, and
scveral mitoses may be seen in this layer near the site of the wound. The
longitudinal muscle layer needs only to align itself somewhat to be continuous
over the wound. X 150.
6 Transverse section of a completely healed uterus 4 days after operation.
There is no scar and no indication of the site of the wound; t h e uterus is
indistinguishable from an unoperated uterus. X 120.
7 Portion of a transverse section of a uterus adhered t o the inguinal f a t
(shown above and to the right of the uterus). Extension of the tunica propria
into the f a t is shown. The endometrial and scrosal rpithelia a r e reflected over
the fat. x 200.
WOUND HEALING IN MOUSE UTERUS
PIATE 1
CHARLES WRIGHT UOOKBR
227
PLATE 2
EXPLANATION OF FIGURES
8 Healing i n a uterus with adhesions of both mings t o the f a t . 1iir:ision of
the f a t hy the t u n k i p ~ o p r x iis shown. Extensions of tuiiica propria f r o m both
wings have fused closing tlic utrrine luinen. The eudonietrial epitlieliuni of both
wings has gronn over thew extensions but has not nict as yet. Reflection of the
serosal epithelium over the f a t is shown on the left side. X 150.
9 Mechanical blocking by f a t which is opposing approxiniation of the t v o
wings of the slit utcxrus. On thr left the cut edge is covered by cpitlieliuin continuous with both the endometrial and serosal epithelia. A branch froin the
c.ndoinetria1 epithelium is reflected over the f:it. X 180.
10 d section of a uterus to which allantoin was applied a t the time of operation.
The cndometriuni is thickencd and somewhat rdcmntous. The cut ends of the
myometrium ai e scparatrd by scar resulting froiu fibroplasia. in the tunica
propria. X 75.
11 A section of an :illantoin treatrd uterus. The ends of thr in!,ornetriuni
are widely separated and thr wound has healed by sear formation. The tuniea
propria is greatly thickened. X 40.
12 A sectiou of the utcrus of rz mouse rrreixing progesteronc. The n i p
metrium is widcly separated 11)- a war iesulting froin fihroplasia i n the tunica
1nopri:i. X 8.5.
228
WOUND HEALING IN MOUSE UTERUS
CHARLES WRIGHT UOOKBR
PIATE 1
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