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The rate of uterine growth resulting from chronic distention.

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THE RATE O F UTERINE GROWTH RESULTING FROM
CHRONIC DISTENTION
SAMUEL R. M. REYNOLDS * AND SANFORD KAMINESTER
Department of Physiology, L o n g Island College of Nedicine, Brooklyn
THREE FIGURES
Certain growth changes take place in the uterus of an untreated, ovariectomized rabbit when this organ is distended
with a pellet of suitable size. It has been found (Reynolds
and Kaminester, '36) that the pellet should be more than half
yet less than twice the size of the uterus in order that appreciable growth takes place. The largest growth response is
obtained when the pellet and uterus are of approximately equal
sizes. These relationships were ascertained f o r a distention
period of 2 weeks, commencing 1 week after ovariectomy. No
evidence was obtained on the rate at which the growth responses in the uterus take place, nor was it ascertained that
growth was complete at this time. The present experiments
furnish this information.
PROCEDURES
The experiments were of two types. I n the first group, two
or three paraffin pellets (m.p. 56") were inserted per vaginam
into the uteri of mature rabbits in the manner described before
(Reynolds and Kaminester, '36). At stated times after insertion of the pellets the distention sites were taken, fixed and
studied, both for the histological features and the amount of
Aided by a grant from the Committee for Problems in Research of Sex, National
Research Council.
* Fellow of the John Simon Guggenheim Memorial Foundation.
Member of the Department of Obstetrics and Gynecology, Long Island College
of Medicine.
281
282
S. R. M. REYNOLDS A N D S.
KAMINESTER
increase in gross size of the tissues. Comparison of these
changes in the distention sites was made with segments of
untouched, undistended parts of the corresponding uteri. The
times a t which the tissues were taken after insertion of the
pellets were a ) immediately after distention (acute distention); b ) 24 hours after distention; c ) 4 days and d ) some
additional distention sites were taken on the fourteenth day
i n order to confirm and extend the earlier series (Reynolds
and Raminester, ’36). The method by which the growth resulting at the distention sites was estimated has been described
before. Similarly, the method by which the degree of distention was ascertained has been reported ; briefly, it consists
of determining the ratio of the cross sectional area of the undistended part of a uterus (including its lumen) to the crosssectional area of the distended pellet. Thus, a 1: 1 (1.0) distention ratio means that the uterus and pellet are of equal
CI’OSS sectional areas ; a 2 : 1 (2.0) ratio means that the uterus
is twice the size of the pellet and a 1: 2 (0.5) ratio, that the
uterus is one-half the size of the pellet. The size in each case
is determined by plaiiimeter measurements of camera lucida
drawings of average cross sections.
The second groixp of experiments differed from the first
in the method of distention employed and were performed in
order to obtain information regarding the capacity of the
uterus of the untreated, ovariectomized rabbit to become
adapted to progressively increasing distention, as the uterus
must do in the more complex state of pregnancy. Instead of
iising paraffin pellets of constant size as in the first group of
experiments, fluid was allowed to accumulate in the lumen of
the uterus between two ligatures placed about an inch apart.
I n this way, the uterus was progressively distended, although
the rate a t which fluid accumulated is not linown. After 4 days,
the distended segment (along with an undistended portion of
uterus for control purposes) was fixed with the fluid in situ.
T t was possible to ascertain the end amount of distention in
each instance, and of course the growth increments in the
tissues were measurable a s before.
UTERINE GROWTH A N D CHRONIC DISTENTION
283
RESULTS
Acute diste9ztio.n. As noted already, the histological
features associated with acute distention show that there is
considerable loss of fluid and blood from the tissues about
the pellet. With the larger degrees of distention, the endometrium is reduced t o a thin layer in which the epithelium
rests upon the myometrium in some places. The myometrium
is thin and avascular. Rarely, small hemorrhages may be
seen, but otherwise there is little evidence of trauma. Measurements from six sites at which the distention ratio was 1.0 or
less show that a reduction in size of the tissues of 18 to 357%
takes place. The immediate effect of distention, therefore, is
to force blood and tissue juices from the distention sites.
T w e d y - f our hours after disteiztioqi. Figure 1 shows that
by the twenty-fourth hour o r thereabout after insertion of the
pellets, eleven out of fourteen distention sites regained or
exceeded by a little their original size, as gauged by comparison with untouched, undistended parts of the same uteri.
The impression that one obtains from studying these tissues
under the microscope is that the changes which take place during the first 24 hours of distention consist of a restitution of
the fluid matrix of the tissues ; ordinary histological methods
fail to show any sign of cellular growth such as may be
demonstrated on the fourth day and later, as described below.
Distenti0.n for 4 days and longer. I n figure 2, the percentage
increases in size of the various distention sites after 100 hours
of distention are shown (triangles), along with the growth
after 14 days of distention (dots). These points, through their
manner of distribution, show that by the fourth day of distention, the size of the tissues about the pellets is as large as it
will become, with this mode of distention. At least, no increase in size is found to take place between the fourth and the
fourteenth days of distention. I n confirmation of the earlier
data (Reynolds and Raminester, ' 3 6 ) ,the present results show
that the pellets are effective stimuli for growth when they are
more than half the size of the undistended uteri, and that
maximal growth responses are obtained when the pellet and
284
S. R. M. GEYNOLDS AND S. KAMINESTER
the uterus are of approximately equal sizes. With still larger
degrees of distention, the pellets are less and less effective as
growth-promoting stimuli. The reasons for this have been
discussed elsewhere (Reynolds and Allen, '37).
I n addition to the fact that the gross enlargement of the
tissues is achieved by the fourth day after distention is the
further fact that the histological changes resulting from iiisertion of the pellets are also completed by this time. The
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Uterus. Pellet Ratio
Fig. 1 Chart showing the size of distention sites relative to non-distended sites
of rabbit uteri, expressed as percentage of the latter. Correlated with the amount
of distention in each case. 9 distention ratio of 2.0 means that the uterus was
twice the size of the pellet; of 1.0, the uterus and pellet were of equal size; of 0.5,
the uterus was half the size of the pellet. Similarly for other figures. Time of
distention, 24 hours.
Fig.2 Chart showing growth of chronically distended uteri after 4 days
(triangles) and 14 days (dots). Paraffin pellets were used, 4 inch in length and
of known, uniform diameters. No increase in size of uteri between the fourth
and fourteenth days. See text for description of histological features.
Fig. 3 Chart showing the effect of progressive, increasing distention (curve A )
by accumulation of fluid in the lumen of uteri; distention period, 4 days. Curve B,
redrawn from figure 2.
UTERINE GROWTH AND CHRONIC DISTENTION
285
cells of all parts of the tissues about the pellets undergo
marked hypertrophy, as shown by an increase in ratio of cytoplasmic t o nuclear material; the nuclei become vesicular ; the
vascular bed is somewhat increased; the tissues are edematous, especially in the deeper portions of the endometrium,
and hyperplasia, even of the smooth muscle (Allen, et al., '37),
takes place.
These results show, therefore, that the initial response of
the uterus to distention is to replace the tissue fluids lost as
a result of insertion of the pellets. Then, according to the
effectiveness of the degree of distention, growth changes are
evident in all the tissues. These structural changes are largely
complete in less than 4 days, so far as may be judged by these
experiments. Evidence has been presented elsewhere which
shows that the essential nature of the distention stimulus is
the creation of an appropriate increase in tension upon the
tissues (loc. cit.), but if the tension becomes too great, the
nutrition of the tissues may be impaired through impoverishment of the blood supply.
Progressive distention by accumulation with fluid. I n this
group of experiments the least amount of distention obtained
exceeded a uterus : pellet ratio of 1:1.59 (distention ratio of
0.63) or, as shown in figure 3, a point far down on the right
of curve B, redrawn from figure 2. I n contrast t o curve B,
curve A of figure 3 shows that the growth responses increase
in amount as the distention increases, as far as the data go.
The greatest growth response was one of 255% increase, or a
three and a half-fold increase, at a distention ratio of 1:12.5
(i.e., the pellet was 12.5 X the size of the undistended uterus).
This is the largest amount of stretching obtained thus far in
untreated, ovariectomized rabbits, and was possible only because the uterus grew as it became increasingly distended.
Clearly, therefore, when the uterus is progressively distended it is capable of both rapid and extensive adaptive alterations in structure pari passu with the increasing distention.
Mention may be made in passing of the extent of uterine
growth which takes place in the rabbit during pregnancy.
286
S . R. M. REYNOLDS AND S. KAMINESTER
Hammond’s data ( ’ 3 5 ) on this subject show7 that a five- to
eightfold increase takes place. This figure compares favorably
with that stated by Stieve (’32). I t is striking, therefore, that
the three and a half-fold increase that was observed in the
instance cited above took place in 4 days, and in the absence
of ovarian or other hormones associated with gestation. The
role of distention during gestation has been discussed in two
other places (Reynold’s, ’37 a, b).
SUMMARY
The rate of the changes in uterine structure and size resulting from chronic uterine distention is described. It i s
found that the growth changes, including both hypertrophy
and hyperplasia, even of smooth muscle, are completed in less
than 4 days after insertion of paraffin pellets of uniform and
known sizes. It is further observed that when distention is
achieved by progressive accumulation of fluid within the
uterus the growth response is proportional to the degree of
distention, a s f a r a s the data go. It is further found that the
percentage increase in size of the uterus of the untreated,
ovariectomized rabbit under the latter conditions approaches
in some instances that which takes place during normal
pregnancy in the rabbit.
L I T E R A T U R E CITED
ALLEN,EDGAR,
G. W. SMITH A N D 6. R. M. REYNOLDS 1937 Hyperplasia of smooth
muscle. Proc. Sac. Exp. Biol. and Med. ( I n press.)
HAMMOND,
J. 1935 The rliaiiges in the reproductive organs of the rabbit during
pregnancy. Trans. Dynamics of Development, vol. 10, pp. 93-115.
REYNOLDS,S. R. M. 1937 a Chronic uterine distention and its relation t o the
end of gestation. Am. J. Obst. Gynec., vol. 33, pp. 968-978.
1937 b Harmonic and physical factors i n uterine growth. Symposia
on Quantitative Biology, vol. 5 (in press). Published by the Biological
Laborator), Cold Spring Harbor, L. I.
REYNOLDS,
S. R. &I., A N D W. AT. ALLEN 1037 The effect of progestin on t h r
growth response of the uterus t o chronic distention. Anat. Rec., vol. 68,
pp. 481-488.
REYNOLDS,8. R. II., AND 8. K.4hlINESTER 1936 Distention, a stimulus for
uterine growth in untreated, ovariectomized rabbit. Am. J. Physiol.,
VOI. 116, pp. 510-515.
STIEVE,H. 1932 Uber die Neubildungen von Muskelzellen in der Wand der
schwangeren menschlichen Geblrmutter. Central. f. Gydkol., Bd. 56,
S.1442-1447.
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