Cytology of Human Uterine Glands in Gravid
and Mon-Gravid Phases.
By
Olive E. Aykroyd and J. Bronte Gatenby,
Zoology Department, Trinity College, Dublin.
With Plates 23-26 and 3 Text-figures.
CONTENTS.
INTRODUCTION .
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541
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543
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543
TECHNIQUE
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MATERIAL
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PREVIOUS W O R K
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OBSERVATIONS—Recognized Phases in the Uterus, p . 544. Structure
of Glands, p . 544. Cell Types in the Uterine Gland, p . 545. T h e
Typical Uterine Gland Cell of t h e non-Pregnant Period, p . 545.
F a t , p . 547. Glycogen, p . 548. Mitochondria, p . 548. Menstrual
Period, p . 549. Proliferative Period, p . 550. Progravid Period,
p . 550. Gravid Period, p . 550. Summary of Cytological Changes
in Uterine Glands, p . 552. Secretions, p . 552. Elimination of
Cells from t h e Uterine Gland in t h e non-Menstrual Period, p . 553.
Stroma cells, p . 555. Identification of Curettings from Pregnancy
Cases
555
DISCUSSION
SUMMARY .
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LITERATURE CITED
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556
558
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560
INTBODUCTION
SINCE the valuable studies of Hitsehmarm and Adler in 1908,
and Schroder from 1909 to 1914, there have been many reinvestigations of the human uterine gland during the menstrual
cycle. The opportunity which we have had of studying material
from three early pregnancies has led us to re-examine the nonpregnant cycle. The new Aoyama method combined with the
thoroughly satisfactory Sudan IV fat technique of Kay and
Whitehead (1935) has given us an improved type of preparation.
It seems safe to say that in no other organ in the mammalian
body is there normally a greater degree of cell activity than in
NO.
328
N
n
542
OLIVE E. AYKKOYD AND J. BEONTE GATENBY
the uterine glands. At the proliferative phase of the cycle the
number of visible mitoses in any section is even greater than in
the active testis. The glandular secretion of the uterine crypt
cells is unlike anything known in other organs, for there appear
to be three possible types of secretion at different epochs of the
cycle.
This work has been made possible through the interest shown
by Dr. Ninian Falkiner of Dublin. We have received from him
thirty-three specimens of non-pregnant material, and three early
pregnant specimens. Dr. Falkiner has been most helpful with
advice and criticism. Dr. O'Donel Browne also sent us two
specimens.
Dr. Gerald Dockeray of the Eotunda Hospital Laboratory
very kindly showed us his excellent collection of normal and
pathological specimens, which was of considerable help to us.
One of us (0. B. A.) received a grant-in-aid from the Irish
Medical Eesearch Council. The latter also provided a grant to
cover certain laboratory expenses. We thank the members of
the Council for their assistance.
TECHNIQUE.
Except where other methods are indicated (e.g. Carnoy,
Eegaud, Weigl, Kolatchew, &c.) the routine technique was
fixation in Aoyama's fluid. Sent to the laboratory, the pieces
were treated in several different ways:
1. Carried through Aoyama's method for the Golgi apparatus,
imbedded in wax, and often counter stained in Mann's methyl
blue eosin after toning.
2. Carried through Aoyama's method up to the reduction
stage, then cut on the freezing microtome, stained in Sudan IV
for the fat and mounted in glycerine jelly.
3. Washed out well in water and osmicated (Sjovall's method).
4. Upgraded and imbedded without silvering. Stained in iron
alum haemotoxylin, mucicarmine, or muchaematin.
Mucisudan, a new stain for mucin as described by Leach
(1938), was used with success. We also used Eegaud, Helly,
Feulgen, and the various routine methods.
Two endometria were conveyed to the laboratory in warm
HUMAN UTERINE GLANDS
548
isotonic saline and ultracentrifuged for half an hour. Movements
of the cytoplasmic bodies were not, however, apparent, and this
work will have to be repeated at greater velocities.
MATERIAL.
Altogether thirty-eight endometria were examined. Some
were removed by curetting and others by hysterectomy.
Only two specimens were available from the menstrual phase.
One specimen was removed on the sixth day, but showed no
evidences of post-menstrual repair.
From the proliferative phase there were eleven pieces of
endometria and fifteen were removed in the progravid period.
Because of the irregularity of cycles, in some cases it only
became possible to state from what phase the specimens came
after cytological examination.
The glands of three early gravid uteri were studied, the oldest
of these being six weeks pregnant and the others two or three
weeks.
PREVIOUS WORK.
The classic description of the cyclical changes in the human
uterine glands is that of Hitschmann and Adler (1908). These
observers showed that a definite series of changes took place
implicating both uterine epithelium and glands. Except for the
fact that they considered that the uterine epithelium at menstruation remained intact, a view shown subsequently to be
wrong by Schroder (1914), Bartelmez (1933), and Falkiner (1932),
their description of the cycle has been confirmed by subsequent
observers.
Neither Hitschmann and Adler nor Schroder described the
cytology of the uterine cycle, but this deficiency was made good
by Bartelmez and Bensley (1932), whose account has been
largely confirmed by the present writers. To all intents and
purposes there was no previous work on the cytology of the
human glands before the work of Bartelmez and Bensley, but
such observations as were made previously have been referred
to by them. We do not propose to enter into work previous to
that of Bartelmez and Bensley. These authors have described
544
OLIVE B. AYKROYD AND 3. BRONTE GATENBY
glycogen, mitochondria, Golgi bodies, and, to a certain extent,
fat. They have given an adequate description of central bodies,
and the ciliated cells. Their account of the secretion of the
glands within the menstrual cycle is satisfactory, but does not
extend to the basalis during menstruation, or to the glands at
pregnancy.
Elsewhere we have mentioned the work of Dr. Catherine Hill
(1933) on the uterus of P l a t y p u s and E c h i d n a .
Many accounts of the histology of the endometrium exist. Of
these the most detailed is that of O'Leary (1929), who described
the structure of the glands at all stages of the cycle.
OBSERVATIONS.
E e c o g n i z e d P h a s e s in t h e U t e r u s .
We have decided to adopt the following interpretation of
phases:
(a) Proliferative Period, beginning with the fifth or sixth day
after the onset of menstruation, and lasting to about the fourteenth day.
(b) Progravid Period, from the fifteenth to the twenty-eighth
day.
(c) Menstrual Period, first to third or fourth day.
(d) Post-menstrual Period, fourth or fifth day.
In addition there is the Gravid Period, or Period of Pregnancy.
The time when this becomes marked in terms of cytologieal
change in the uterine glands is uncertain at present, but a
possible means of identification has been suggested in this paper.
S t r u c t u r e of G l a n d s .
We agree that the glands can roughly be divided into two
parts, an outer towards the lumen of the uterus called the
f u n c t i o n a l i s , and a deeper, overlying the myometrium,
known as the basalis. During menstruation, the chief area of
crumbling away is the f u n c t i o n a l i s ; whereas, during regeneration, cells derived from the b a s a l i s are particularly
active. The functionalis area cells contain more secretory
elements than the basalis.
HITMAN UTEEINB GLANDS
545
Cell T y p e s in t h e U t e r i n e G l a n d .
Three types of cells have been recognized by some recent
workers, and are given in order of frequency: secretory, ciliated,
and rod cells.
It is quite true that shrunken, often more darkly staining rod
cells are common, especially in the interval (proliferative phase),
but we believe that all stages between what are called rod cells
and secretory cells exist. The rod cells are not cytologically
different from the secretory cells except in size and stainability,
both differences being due to the fact that they are degenerating.
At least this is the conclusion we have adopted at the present
moment. Nor do we find any cytological difference between
ciliated and non-ciliated secretory cells except for the possession
of cilia by the former.
We can add little to the description of ciliated cells given by
Bartelmez and Bensley in 'Special Cytology' 1932. We find
ciliated 'hydropic' cells to be more common during the proliferative period, and consider them to be cells just about to
undergo mitosis. The fact that their Golgi apparatus impregnates in the form of large granules shows that they are in a
condition preparatory to dictyokinesis.
The T y p i c a l U t e r i n e Gland Cell of t h e n o n - P r e g nant Period.
In Text-fig. 1 are two typical progravid cells from the intermenstrual period of the non-pregnant human. One cell is ciliated, but otherwise is not different from other cells lining any
gland. The most remarkable and reliable cell structure other
than the nucleus is the Golgi apparatus (G.A.). We have found
that it undergoes the most definite series of changes of any cell
organ in any given stage of the menstrual cycle. In the progravid section shown in fig. 13, PI. 25, it will be noted that the
Golgi apparatus (G.A.) seems to form an intercommunicating
palisade from cell to cell. Actually, we have no evidence that
there is any intercellular connexion, but pieces of the Golgi
apparatus impinge against each cell wall in many cases. The
apparatus at this stage is a typical anastomosing net, which
varies a little in degree of contraction in different cells. Besides
546
OLIVE B. AYKEOYD AND J . BRONTE GATENBY
the Golgi apparatus are many scattered mitochondria (M.);
these are chondriomites mostly, but some are granular in
appearance.
The base of the cell has a definite basement membrane (B.M.),
--C1L,
fr-BB
TB
TEXT-FIG. 1.
Two typical progravid cells one of which is ciliated (en,.). Each
cilium has a basal body (B.B.) and behind the cilia is an inner
structure (i.s.). The other cell has watery blebs (BL.). The Golgi
apparatus (G.A.) is a loose juxtanuclear net. Fat (P.), mitochondria
(M.), and glycogen (GLY.) are scattered through the cell, T.B.,
terminal bead; CEN., centriole; B.M., basement membrane;
B.s.c, stroma cell.
and here and there are stroma cells (B.S.C.) which have become
partly flattened against the basement membrane: special basement membrane cells do not appear to exist, the cells which we
have found being apparently intercontinuous with the other
stroma cells.
HUMAN UTERINE GLANDS
547
At the outer pole of the cells, facing the gland lumen, the cell
wall is thickened where the cells meet, and a definite bead (T.B.)
can be seen. Thus the margin of the cell is thickened, and where
the cells meet, the marginal line is brought out into blebs (BL.).
The enclosed centre of the lumen face of the cell is formed of a
delicate cell wall. In those rarer cells which are ciliated there is
usually a very definite palisade of basal bodies (B.B.) from each
one of which a cilium protrudes. Below the basal bodies there
appears to be an inner structure (i.s.) within the cell protoplasm,
which in some examples almost appears as inward continuations
of the cilia. The area, however, is probably a definite region of
the cytoplasm, and not the inwardly continued ends of the cilia.
One or sometimes two centrioles (CEN.) lie between the nucleus
and the Golgi apparatus—and not in the substance of the latter.
We now come to the much less definite cell inclusions, which
vary quite considerably not only in the different epochs of the
intermenstrual history, but also in individual cases within a
definite epoch. We refer to the fat and glyeogen.
Pat.
All the endometria were by routine sectioned on the freezing
microtome, and stained with Sudan IV. In the proliferative
stage of the cycle, the cells are devoid of sudanophil fat, except
for occasional droplets to be seen in the neighbourhood of the
Golgi apparatus. The fat first appears as small granules in the
base of the cells during the early progravid phase. It gradually
increases in amount, but, in general, remains in the basal
position, except for a few scattered droplets throughout the cell
(fig. 4, PL 23). Many glands have no fat at all, especially in the
basalis region, and the quantity may vary in different parts of
the same gland. One progravid specimen contained large
amounts of fat in the gland lumina, but this was considered to
be abnormal.
If pregnancy supervenes, both the glandular epithelium and
the uterine epithelium become laden with large droplets of
sudanophil fat (fig. 11, PI. 24 and fig. 12 F, PL 25), which are still
present at the six weeks gravid stage. Bartelmez and Bensley
(1932) found that the base of the glands stained a faint pink
548
OLIVE E. AYKROYD AND J. BRONTE GATENBY
with Sudan III, but that granules were not distinguishable.
This we believe is due to the inferiority of the Sudan III
method as a stain for fatty substances.
If menstruation occurs, the fat passes out of the cells into the
lumina, and is carried away with the rest of the detritus.
Glycogen.
The number of specimens fixed to preserve glycogen was four.
Best's carmine with the spit test as a control was found to
demonstrate glycogen very beautifully after fixation in Carnoy
and double imbedding in celloidin and wax.
The quantity and distribution of the glycogen varied considerably, and it is impossible to draw satisfactory conclusions
from the limited amount of material available. One endometrium of the proliferative phase showed little glycogen at the
bases of the cells, and of two removed during the progravid
phase one had large amounts and the other practically none.
There was one specimen from the sixth day after menstruation.
All the glands in this contained large quantities of glycogen
situated in basal vacuoles, and the gland lumina were full of
small droplets (GLY., fig. 8, PI. 24 and fig. 14, PI. 25). In many
specimens fixed in Aoyama, large basal vacuoles are to be found
in the gland epithelial cells. These are probably formed by plasmolysis of the glycogen, which is in a labile condition.
It was not found possible to demonstrate fat and glycogen
side by side in the same cell because of fixation difficulties, but
in the progravid specimens containing large basal vacuoles, it
was found that there was not so much fat present as in those
without the vacuoles. This might suggest an active change of
one substance into the other depending on the requirements of
the cell.
Mitochondria.
The mitochondria are best studied after Eegaud fixation and
staining with iron alum haematoxylin. Sometimes, however,
they are very clearly impregnated by the silver techniques.
During the proliferative phase the mitochondria are in the
form of filaments arranged more or less parallel to the axis of the
cell. At the progravid period the majority round up and become
HUMAN UTERINE GLANDS
549
irregularly scattered through the cell. In the gravid cell the
mitochondria are all rounded and swollen, and occasionally show
basal zoning.
Menstrual Period.
The specimen of a second day of menstruation shows clearly
the well-known picture of extravasated blood, loose groups of
crumbling functionalis gland cells, and surviving basalis areas.
In fig. 17, PL 26, is shown one of these areas imbedded in stroma,
but undergoing definite changes. Two types of cells are visible,
one marked D.C. with a diffuse Golgi apparatus (G.A., fig. 1,
PL 23), the other devoid of other cell contents and possessing
the very characteristic Golgi apparatus shown in fig. 17, R.C.,
PL 26, and at a higher magnification in fig. 2, PL 23. Nothing
like these two types is found at any other stage, and this applies
most definitely to the dispersed phase shown in fig. 1, PL 23.
A possible view is that these cells have suddenly produced
secretion, for they bear a close resemblance to gland cells of
other organs known to be in the dispersed phase of secretion.
We believe that the subsequent stage shown infig.2, PL 23, and
in fig. 17, R.C, PL 26, is the recovery phase, and leads quite
normally to the cells shown in fig. 3, PL 23, in which the Golgi
apparatus (G.A.) is proliferating.
The question of a secretion at this phase has puzzled us
greatly, and we have not enough material to come to a definite
conclusion. In Aoyama sections counterstained in Mann's
methyl blue eosin, the lumen of the basalis glands contains at
least three materials—firstly a central core of mucin-like material which stains blue, and nearer to the cells a vacuolated mass.
The vacuoles are clear, the trabeculae between the vacuoles
more or less granular and resembling somewhat the ground
cytoplasm of the actual cells. In some areas, the actual outer
fringe of the cells appears to contain fine secretion granules, the
nature of which is very doubtful.
In other words, we believe that at this period the Golgi
apparatus suddenly disperses, and much of the cell contents is
deposited in the lumen of the gland. Subsequently, from fragments of the Golgi apparatus, the type shown in fig. 2, G.A.,
550
OLIVE B. AYKEOYD AND J. BRONTE GATBNBY
PI. 23, is built up. In the deeper basalis areas there is very little
mortality among the gland cells, and all of them show the
dispersed changes in the Golgi apparatus. In such areas the
lumen of the gland rarely contains red blood corpuscles, but in
the strands of crumbling functionalis the lumina are choked
with red blood corpuscles. We have no reason to suppose that
our specimen is abnormal, and the cell picture fits in admirably
with the later stages we have examined. We have studied
neither the glycogen nor mitochondria of this period.
Proliferative Period.
The proliferative phase is marked by the growth and coalescence of the granular postmenstrual Golgi apparatus to form the
typical Golgi net (fig. 3, G.A., PI. 23, and Text-fig. 3 B and 3 C).
The mitochondria (M.) became more easily demonstrable, and
the whole cell passes from a cubical to a columnar shape.
Numerous mitoses occur, and odd droplets of fat make their
appearance.
Progravid Period.
The progravid phase is illustrated in fig. 4, PI. 23, and fig. 13
and fig. 19, PL 26. The two first-mentioned figures are typical.
In fig. 4, PI. 23, at R, is a 'rod cell', which was discussed on page
545. The progravid condition is one of complete establishment,
no change taking place unless to the menstrual or the gravid
condition. Pat is nearly always present at the base of the cells
(fig. 4, F., PI. 23), and glycogen (GLY.) has been found (fig. 7,
PL 24) in the form of droplets also mainly at the base of each
cell. The outer or lumen end of the cell often shows the blebs,
figured in Text-figs. 1 and 2, BL., which seem to contain a watery
secretion, and which become shed or budded off into the lumen
of the gland. No granular secretions have been found in the
outer pole of the cells. Glycogen is usually present in the gland
lumina, but whether it is a normal constituent of the secretion
at this stage is impossible to state.
Gravid Period.
The progravid gland either breaks clown to produce the
menstrual phase shown in fig. 1, PI. 23, and fig. 17, PL 26, or it
551
HUMAN UTBEINB GLANDS
passes on to the gravid stage shown in Text-fig. 2, fig. 9, PI. 24,
and figs. 12,15, PL 25 and fig. 16, PL 26. At the progravid stage
the cells have become more cubical than columnar, and at
GLY
TBXT-FIG. 2.
Typical gravid cell. Secretion (s.) lies in the meshes of the Golgi
apparatus (G.A.) and some is being extruded from the cell. Other
lettering as in Text-fig. 1.
pregnancy they are quite cubical, as is shown in the abovementioned figures and photographs.
The gravid uterine gland cells now produce a completely new
type of secretion, which is clearly shown in Text-fig. 2 and fig.
16, s., PL 26; other cells are drawn with the camera lucida in
fig. 10, s., PL 24. The secretion is in the form of irregular ovoid
droplets, and occupies the outer folds of the Golgi apparatus, as
shown in fig. 10, G.A., PL 24. The secretion certainly appears in
552
OLIVE E. AYKEOYD AND J. BEONTE GATENBY
close topographical connexion with the Golgi apparatus, though
no sort of break-up of the latter has been seen.
The secretory droplets pass out of the uterine gland cells into
the lumen. The mitochondria are swollen and are scattered
irregularly throughout the cells except for some which show
basal zoning. A very large amount of fat is found in the gravid
uterine gland cells (figs. 11, PL 24 and 12, P., PI. 25). The
glycogen content has not been studied by us, but previous
workers have found great quantities during pregnancy.
S u m m a r y of C y t o l o g i c a l Changes in U t e r i n e
Glands.
In Text-fig. 3 is a pictographic illustration of the present
writers' views on the cycle in the uterine glands. In A, the
menstrual phase, the cells of the basalis are ejecting much of
their contents; the Golgi apparatus (G.A.) has broken up and the
fat (F.) has left its position at the base of the cell and is principally found in front of the nucleus. The complete crumbling of
the functionalis takes place. After this process of evacuation,
the post-menstrual phase shown in B is reached, the cells being
limpid and cubical, the Golgi apparatus (G.A.) in the very
characteristic form of a number of granules arranged in a line
above the nucleus. Eegeneration of the functionalis and uterine
epithelium is taking place. Subsequently in C, the proliferative
phase, the Golgi apparatus becomes a more normal net, and the
cell once again columnar. Very little fat is present. The glands
are growing, but are still straight. In the progravid phase, D,
fat and glycogen collect principally in the base of each cell, the
cells become less columnar, and the gland assumes the dentate
and scalloped appearance so characteristic of this phase. Should
pregnancy supervene, the gland cells assume the gravid phase
shown in E, in which there is a further collection of storage
granules, and the appearance for the first time of a definite
secretion, probably proteid in nature, and topographically related to the Golgi apparatus. In the event of pregnancy not
taking place, the menstrual phase, A, recurs.
Secretions.
The secretions from the uterine gland cells may possibly be
HUMAN UTERINE GLANDS
558
three: 1. A thin mucus produced by the outer region of the cell,
and without noticeable intracellular activity of mitochondria or
Golgi bodies. It is likely that the detached blebs and vacuoles
are symptomatic of this process. 2. A copious secretion or
extravasation from the remaining basalis cells at menstruation
accompanied by a breakdown or loosening out of the Golgi
apparatus. 3. A very definite granular secretion at pregnancy,
and limited to the gravid state.
The question of a mucous secretion has worried us considerably. Mucus, as understood by the copious secretions of the
cervix and vagina, does not occur in the uterine cavity. Dr.
Wigham of the Pathology Department, Trinity College, has
informed us that mucus, as above indicated, is not found in the
uterine cavities of autopsy material. Our findings, by using the
muchaematin and mueicarmine methods, show that a positive
reaction for mucus is found in the gland lumina all the time, but
more during the progravid stage and a great deal at pregnancy.
It seems certain that a thin mucous secretion does occur in
the uterine glands and lumina, but not to the same degree either
in bulk, and probably in thickness, as in the cervix and vagina.
In fig. 18, PI. 26. is a photograph of a section of the cervix showing a very typical mucous gland cell with basal compressed
nucleus (GL.). We have found nothing comparable in the
uterine glands, and have been obliged to conclude that they are
not arranged for the mass production of mucus. But we cannot
deny that material which gives a positive reaction with the usual
mucous stains always exists in the gland lumina.
E l i m i n a t i o n of Cells f r o m t h e U t e r i n e Gland i n t h e
non-Menstrual Period.
In fig. 19, PI. 26, is an early progravid gland showing three
stages in the elimination of rod cells, as has already been described by Albrecht and Logothetopulos (1911). Bartelmez and
Bensley (1932) remark, 'One can readily find transitions between cells which seem normal except that they stain more
intensely than their neighbours, and slim rods which are homogeneous in most preparations. In Feulgen material, however,
only the nuclei react positively. Occasionally bizarre pictures
554
OLIVE B. AYKROYD AND J. BRONTE GATENBY
A.
-CA
D.
E.
GRAVID
TEXT-FIG. 3.
Diagram of uterine gland changes:
A. Menstrual phase. The Golgi apparatus (O.A.) is broken up and
vacuolated. Some fat (r.) is scattered through the cell.
B. Postmenstrual phase. The Golgi apparatus (G.A.) consists of a
few granules which are reorganizing, si., mitochondria.
HUMAN UTBEINB GLANDS
555
are produced as in a ease in which proliferation continued
despite the progravid development of the gland cells. Here it
would seem that the rod cells are degenerating.' In fig. 19, PL 26,
the lumen of the gland contains many expressed 'rod' cells. It
seems possible that in Miss Hill's study of the Monotremata
(1933) part of the coagulum found in the glands may be formed
of expressed cells.
Stroma cells.
The Golgi apparatus of some stromal cells is shown in figs, o
and 6, PL 23. During the proliferative phase the cells are small
and the Golgi apparatus condensed. The cells increase in size
during the progravid period, and the Golgi apparatus loosens
out. If pregnancy supervenes the cells continue to grow until
a decidua is formed.
The quantity of fat present in the stroma varies as in the
glands. It is greatest during the progravid and gravid periods.
At menstruation scattered stromal cells are found heavily laden
with fat while the majority of cells are fat-free.
The mitochondria are similar to those found in any connective
tissue cell.
I d e n t i f i c a t i o n of C u r e t t i n g s from P r e g n a n c y
Cases.
The appearance of proteid secretions (s.) shown in fig. 10, PL
24, fig. 16, PL 26, and in Text-fig. 2 will enable the pathologist to
identify the curetting as having come from a case of interrupted
pregnancy. The exceptions to this rule will possibly be the same
as have been found to hold for the Ascheim-Zondek pregnancy
test, though we have no information on this aspect at present.
Formalin-fixed material stained in Heidenhain's iron alum
C. Proliferative phase. The Golgi apparatus (G.A.) is juxtanuclear
and condensed. The mitochondria (M.) are elongated and arranged
parallel to the polar axis.
D. Progravid phase. The Golgi apparatus (G.A.) is a loosened net.
Fat (F.) and glycogen (GLY.) are situated at the base of the cell.
The mitochondria (M.) are scattered.
E. Gravid phase. Large ovoid droplets of secretion (s.) have
appeared in the meshes of the Golgi apparatus (G.A.). The
mitochondria (M.) are rounded and irregularly distributed.
556
OLIVE B. AYKEOYD AND J. BBONTB GATENBY
haematoxylin demonstrates the granules as dark irregular
bodies.
DISCUSSION.
Two interpretations of the evacuation of cell contents (Textfig. 3 A) in the basalis area at menstruation are possible. One,
that a definite secretion is being produced, the other, that the
cells are preparing themselves for active division and spreading.
We believe that the latter interpretation is the correct one.
During the proliferative phase, when a large number of mitoses
are evident, individual dividing cells contain very little granular
or vacuolar material. Fat is much less in amount, and the cells
are clearer than their neighbours. It is also certain that part of
the Golgi apparatus is evacuated (or dissolved in situ) during
the menstruation phase in the surviving basalis cells, for the
postmenstrual cells emerge with a comparatively much smaller
Golgi apparatus. See addendum.
Bartelmez and Bensley describe as characteristic of menstruation, hydropic degenerating cells which correspond to our' postmenstrual ' cells. These latter are watery and have a broken-up
Golgi apparatus, which we consider is due to the fact that they
are about to undergo mitosis and not because they are degenerating.
The changes shown diagrammatically in Text-fig. 3 A-D are
obviously the preparation of the Golgi apparatus of the gland
cell for the active production of a 'solid', probably proteid,
secretion related to early pregnancy. Similarly, the evacuation
in A is a preparation of the cell for a new and active period of
division, the true glandular facies being unsuitable for this
activity.
Thus, as has been mentioned in the Introduction, the human
uterine gland cell is cytologically one of the most remarkable in
the placental animal.
If, for example, the bulk of the pancreas periodically degenerated, the remaining cells evacuated almost all their granular contents and then underwent a sudden phase of mitosis so as
to regenerate the organ for its secretory functions, we should
have a case comparable with what happens in the uterine gland.
As has been mentioned, the question of mucous secretion has
HUMAN UTERINE GLANDS
557
not been finally settled by us, and we can add little to the
admirable discussion of Bartelmez and Bensley (1932). That a
thin mucus exists in the uterine cavity seems certain from the
work of previous authors and from our own observations. We
have failed to identify a separate category of mucus-producing
cells in the uterine glands, the true mucous goblet cell, such as
is shown in fig. 18, GL., PI. 26, from the cervix uteri, not being
evident. The posteriorly confined nucleus, relatively large
glandular area, reduced or broken-up Golgi apparatus, and
granular contents staining with mucin stains, all undoubtedly
mark the cervix as being composed of true mucous goblet cells.
In some cases the mucicarmine stain does appear to tinge
faintly the lumen end of some of the uterine gland cells, but we
do not place much confidence in the current stains for mucin in
this respect. We have concluded that a thin mucous secretion
is produced from the lumen end of all uterine gland cells, but
have been unable to stain any mucigen granules intraeellularly.
In her study of the uterine glands of P l a t y p u s and E c h i d n a , Dr. Catherine Hill (1933) has concluded that the crypts are
lined with a ciliated epithelium composed of two types of
granule-secreting cells. The more numerous type possesses a
pale-staining oval nucleus which lies in the lower third of the
cell; its chromatin being clumped round the nuclear membrane.
The other type, of much less frequent occurrence, possesses a
darkly staining nucleus, shrunken and pycnotic in appearance,
and situated close to the base of the cell. According to Dr. Hill,
both types of cells produce secretory granules which appear to
be similar, but the cells can be distinguished from each other
throughout the entire secretory phase.
Miss Hill's description accords closely with the results of
current researches on the human uterine glands, as illustrated,
for example, byfig.4, E., PI. 23, in the present paper. As has been
remarked previously, we have been unable to agree at present
that two types of cells do exist in the human glands. We find
in our preparations that the rod cells or 'Stiftchenzellen' are
pycnotic, and to be regarded as stages in the elimination of
effete but ordinary uterine gland cells (refer to Bartelmez's
remarks quoted on page 553). Perhaps the development of
NO. 328
OO
558
OLIVE E. AYKBOYD AND J. BRONTE GATENBY
other staining techniques may induce us to admit that the rod
cells are really comparable with Miss Hill's second category of
cells.
Miss Hill has described a copious (proteid) granular secretion
from the uterine gland cells, which is probably comparable with
the (proteid) secretion materials of the gland cells of the human
gravid uterus.
SUMMARY.
1. After menstruation the basalis regions of the uterine glands
alone persist. The columnar cells evacuate most of their granular contents, and the Golgi apparatus loosens out and breaks up.
(Text-fig. 3 A.)
2. The postmenstrual cells are cubical limpid cells, with a
Golgi apparatus consisting of a few granules arranged in a line.
(Text-fig. 3 B.)
3. In the proliferative phase the Golgi apparatus re-forms and
grows into a characteristic net. The cells become columnar. No
marked aggregation of granules has as yet occurred.
4. In the progravid phase, the cells become cubical, the Golgi
apparatus spreads, and a marked aggregation of fat and glycogen appears at the inner pole of each cell. (Text-fig. 3 C.)
5. Should pregnancy supervene, the cells secrete numerous
ovoid (proteid) granules at their outer poles (Text-fig. 3 D).
These granules are topographically related to the outer edge of
the Golgi apparatus.
6. The presence of the granules in any specimen of curetting
reveals that it has been recovered from a case of interrupted
pregnancy. Exceptions to this might be those which are known
to hold for the Ascheim-Zondek pregnancy test.
7. The uterine glands contain only one type of secretory cell
which may be ciliated or non-ciliated.
Looser network
juxtanuclear.
Enlarged with very Very abundant nil
loose meshes close- through the cells.
ly applied to the
nucleus.
Broken up and vacuolated.
Not
closely applied to
tho nucleus.
A few granules ar- None.
ranged in u Hue
which will reorganise- to farm
prol iterative type.
Progravid.
Gravid.
Menstrual.
Voatmcuqtruul.
Becoming like proliferative.
Small and diWeult
to stain.
Enlarged and
spherical, Irregularly arranged.
Some aro filaments and some
are spherical.
Long filaments arranged parallel to
polar axis.
Mitochondria,
Variable.
Abundant.
Variable but
usually abundant.
A little.
Glycogen,
Nucleus.
None.
Largo ovoid droplets originafco near tho Uol^i
apparatus and pass out
into lumen. Also largo
a7!u>unts of mucicarmino positive material
in lumen.
Cubical.
Variable.
llesemblcs proliferative.
llosombles proliferative.
Resembles proliferative.
Not so tall.
Tall and columnar. Mitoses
numerous.
Morphology of
cell.
In centre of cell.
Volume less.
More of the substance in Usually more
the lumen that reacts spherical and
positively with mucin nearer the censtains. * Blebs' charac- tre of the coll.
teristic. Probably glycogen hi tho secretion.
Substance tu lumen stains Oval. Usually
with mueiearmine and basal but varies.
muuhaematiii.
Secretion,
TABLE OP CHANGES IN THE CYTOPLASMIC INCLUSIONS OF THIS UTERINE GLAND DURING THE MENSTRUAL CYCLE.
A few droplets of
varying size
which appear to
be passing out of
tho coll.
Numerous droplets of varying
size appear at
base oil cell.
None except for
occasional droplets.
Condensed juxtanucleai*.
Prolifcrative.
Fat.
Golgi apparatus.
Phase.
CO
en
560
OLIVE B. AYKROYD AND 3. BRONTE GATENBY
ADDENDUM.
In a letter to 'Nature' (1940), Gillman describes fat changes in
the human endometrium as revealed by Scharlach E. staining.
During the oestrogen phase he found that there was scarcely any
fat in the glandular epithelium, but during the progestogen
phase an accumulation of fat appeared in the proximal end of
the cells. In early pregnancy basal fat was present in increased
amounts. He regards the occurrence of basal fat as a test for the
presence of optimum quantities of progestogen, since it is only
found towards the end of the second half of the normal cycle.
These results are in complete agreement with those given in
the present paper.
LITERATURE CITED.
For further references see Bartelmez, G. W., and Bensley, C. M., in
"Special Cytology" Vol. I l l , 1932.
Albrecht, H., and Logothetopulos, K., 1911. "Lehre v. d. Endometritis",
'Frankf. Ztschr. f. Path.', 7.
Bartelmez, G. W., 1933. "The menstruating mucous membrane of the
human uterus", contrib. to 'Bmb.', 24.
Bartelmez, G. W., and Bensley, C. M., 1932. "Human uterine gland cells",
'Special Cytology', 3.
Falkiner, N. M., 1932. "Menstruating mucosa of the human uterus",
'Ir. Journ. Med. Sc.'.
Gatenby, J. Bronte, and Aykroyd, Olive E., 1939. "Cytology of the
human uterine gland cell", 'Nature', 144.
Gatenby, J. Bronte, and Aykroyd, Olive E., 1941. "Note on the Human
Uterine Glands in the Gravid Phase", 'Proc. Roy. Irish Acad.' 4 6 B. 9.
GiUman, J. 1940. "Fat; an index of Oestrogen and Progestogen activity in the Human Endometrium", 'Nature', 146. 402.
Hill, C. J., and Hill, J. P., 1933. "Development of the Monotremata",
'Trans. Zool. Soc.'.
Hitschmann, F., and Adler, L., 1908. "Bau der Uterusschleimhaut des
geschleehtsreifen Weibes", 'Monatschr. Gebh. u. Gynak.', 27.
Kay, W. W., and Whitehead, R., 1935. "Staining of fat with Sudan IV",
'Journ. Path, and Bact.', 41.
Leach, E. H., 1938. "Anewstainformucin", 'Journ. Path, and Bact.', 47.
O'Leary, J. L., 1929. "Form changes in human uterine gland", 'Am. J.
Anat.', 43.
Schroder, R., 1909. "Drusenepithelveranderungen der Uterusschleimhaut", 'Arch. f. Gynak', 88.
1914. "Zeitlichen Beziehungen der Ovulation und Menstruation",
'Arch. f. Gynak.', 101.
1930. "Weibliche Genitalorgane", Mollendorff's 'Handb. d. Mikr.
Anat. d. Menschen', 7. Berlin.
HUMAN UTERINE GLANDS
561
EXPLANATION OP PLATES 23-26.
Cells all drawn •with the aid of a camera lucida. Magnification X 2,500,
LIST OF ABBREVIATIONS.
GLY., glycogen; M., mitochondria; G.A., Golgi apparatus; F., fat; T.B.,
terminal bead; BL., bleb; B.S.C, stroma cell; CIL., cilia; B.B., basal body;
I.S., inner structure; CEN., centriole; B.M., basement membrane; s., secretion; B., red cell; L., lumen; sr.s., nucleus of stroma cell; D.C, discharging
cell; B.C., recovery cell; GL., gland cell.
PLATE 23
Fig. 1.—Second day of menstrual period. The Golgi apparatus (G.A.) is
broken up and the cell is discharging its contents. Toned Aoyama preparation counterstained in Mann's methyl blue eosin. See fig. 17, PL 26, also.
Fig. 2.—Cells from the same preparation as fig. 1. These cells are designated postmenstrual or recovery cells. The Golgi apparatus (G.A.) is a line
of granules which will reorganize to form the proUferative type of apparatus.
See fig. 17, PL 26, also.
Fig. 3.—Thirteenth day of cycle. Proliferative period. The Golgi
apparatus (G.A.) is condensed and juxtanuclear. Two ciliated cells are
shown. Aoyama preparation.
Fig. 4.—Twentieth day of cycle. Typical progravid cells with enlarged
Golgi apparatus (G.A.) and basal fat (F.). A 'rod' cell (K.) is drawn and also
one cell with cilia (en..). From a combined Aoyama and Sudan IV preparation. See also fig. 13, PL 25.
Fig. 5.—Stroma cells from progravid period. The nucleus is larger than
in the interval phase and the Golgi network (G.A.) is looser.
Fig. 6.—Stroma cells from eighth day of cycle. They are small and their
Golgi apparatus (G.A.) is condensed.
PLATE 24
Fig. 7.—Seventeenth day of cycle. Best's carmine preparation after
fixation in Carnoy. Glycogen (GLY.) is distributed in small droplets throughout the cells and there is some in the lumen.
Fig. 8.—Sixth day of cycle. Best's carmine after fixation in Carnoy.
The glycogen (GLY.) is in larger droplets than in the previous specimen
and at the bases of the cells lies in large vacuoles. There is some also in the
lumen. See also fig. 14, PI. 25.
Fig. 9.—Cells from decidua parietalis six weeks pregnant. The epithelium is low and the Golgi apparatus (G.A.) is enlarged and closely applied,
to the nucleus. Toned Aoyama preparation.
Fig. 10.—Early gravid cells. Mitochondria (M.) are scattered irregularly
through the cell. Ovoid droplets of secretion (s.) lie between the Golgi
apparatus (G.A.) and the lumen. Bleached Sjovall preparation. See also
fig. 16, PL 26.
562
OLIVE B. AYKROYD AND J. BRONTE GATENBY
Fig. 1Z.—Sudan IV preparation of same material as fig. 10. The sudanophil fat (F.) is distributed throughout the cytoplasm. See also fig.
12, PI. 25.
PLATE 25
Kg. 12.—Microphotograph of preparation drawn in fig. 11. F., sudanophil fat; L., lumen. From a frozen section.
Fig. 13.—Twentieth day of cycle. Progravid cells drawn in fig. 4. G.A.,
Golgi apparatus; L., lumen; N.S., nucleus of stroma cell. Toned Aoyama
preparation.
Fig. 14.—Sixth day of cycle. Best's carmine preparation. The glycogen
(ULY.) is in large basal vacuoles and in the lumen of the gland. See also
fig. 8.
Fig. 15.—Early gravid cells. The mitochondria (M.) are black granules.
L., lumen. Bleached Sjovall preparation.
PLATE 26
Fig. 16.—Early gravid cells. Iron alum haematoxylin preparation.
s., proteid secretion.
Fig. 17.—Second day of menstrual period. D.C., cells discharging their
contents. B.C., recovery cells as drawn in fig. 2. N., nucleus; L., lumen.
Fig. 18.—Epithelium of cervical gland. At GL. is a typical mucous
goblet cell with basally compressed nucleus. Mucigen granules black.
Weigl preparation stained with iron alum haematoxylin.
Fig. 19.—Twenty-first day of cycle. I-IV are stages in the elimination
of cells from the uterine epithelium. I I is a 'rod' cell. Iron alum haematoxylin preparation.
Quart. Journ. Micr. Sci.
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