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Histological changes in the epithelium of the human vagina correlated with the menstrual cycle.

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HISTOLOGICAL CHANGES I N THE EPITHELIUllI O F
THE HUMAN VAGINA CORRELATED WITH
THE 3IENSTRUAL CYCLE
BERTRAM G. SMITH
Department of Anuiomy, Unwerszty and Rellecue Hospital Medzcal College,
New Y o r k Unioerszty
EI GHTEEN FIGURES ( FI VE PLATES AND T W O T E X T F I G C R E S )
INTRODUCTION
In most text-books of liistology tlie description of the epitlielium of the human vagina is limited t o the bald statement
that the vagina is lined with stratified squamous epithelium.
In a few text-books this is supplemented by the assertion
that the superficial layers of cells are undergoing cornification. Thus Sobotta (’20, p. 197) writes: “Es . . , . enthiilt
oft auch Eleiden in den oberen Lagen.” Szymonowicz (’21,
p. 337) states : “Die Schleimhant wird bedeckt von einem
. . . . geschichteten Plattenepithel, das in sciiicn oberfliichlichsten Zellagen Eleidentropfchen enthalten kann, also schon
im Vorstadium des Verhornungsprozesses begrifien ist. ”
Schaffer (’20, p. 452) carries the description a little further:
“Die oberfliichlichen Zellen diescs Epithels enthalten Keratohyalinkornchen, ohne dasz cs aber zur Verhornung kiime.
Ein solcho tritt aber bei Schcidenvorfall ein.” I n tlie light of
recent observations of the periodic changes that occur in the
vaginal epithelium, it is evident that the above descriptions
are incomplete in that they cover only certain phases of its
cyclical his tory.
Although cyclical changes have been described in the
vaginal epithelium of certain animals, published records of
observations indicating a similar series of events in the
human species are very limited in number. So f a r as the
317
writer is aware, thcp arc confined to the c ~ o n t r i l ~ ~ t i oofn s
I'apanicolaou ( '24), Dierks ( W ) , and hdler ( '28). Hence
the sitb,ject has not aclraiiced beyond tho stage vTlicre furtlier
civitlmce may lw ac ptable. Tlic prcsent paper is mainly
a coilfirmation of
e of the rcsnlts obtained hy other
workers ; i t differs c1iiefl;v in the mcthocls employed and in
tlic scope of tlie investigatioii. Pnpanic~olaounscd tlic method
of \raginal smears, previonsly employed with great siiccess
(Ktocakard and I'apanicolaon, 'IT) in the study of the oestroiis
cyc~lcin the guinea-pig. IXerlis and Acllci* nsed operative
matcrial obtained from patielits svlio gave information regarcling tlic men ual histor>-; most of these women had
1)ome c~liildrcii. 11)- o w i observatioiis are based on postmortem material, pai.tiewlarly tliat obtained in ii critival
stage from a single nulliparons female aged t\venty-tlirec
years. In this c m e the menstrual history was not obtainaldc.,
I ) i i t since all the internal gcwital organs were preserved, the
stage of the menstrual cycle was readily determined by
c~smiiiiationo f sectioiis of the utcxiiie mwosa.
R E V l E b ' O F THE LJTEliilTURE
I n a hrief paper Papanicolaon ( '24) states :
T h e normal hmnan sriiriirs differ considerably in cellnlar coinposition from those of Ion er aiiinials yet they iicxrthple
typical and characteristic changes which may serve to in
number of distinct stages. The oviila tion iiioment itself i h rc\ raled
t)y w r t a i r i modifications in the s n w r which wi11 be fixlly tlrscribed
in anothrr paper.
The recent important work of Dierks ('27) has demonstrated tliat during tlie intc~rmenstrunmthe epithelium of the
human vagina acquires a nniqne stratification iiivolving the
formation of an intra-epithelial zone of coriiified cells ;
further, that tluriiig mcnsirnatiou the thick layer of cells
siqm5cial to the cornified zone, aiid eventually including the
latter, is shed into the lumen of the vagina. The former
thickness of the vaginal epitlielium is subsequently restored
liy growtli. Like the uterus, tlie vagina becomes congested at
EPITHELIUM OF THE HUMAN T~AGINA
319
the time of menstruation. Thus conditions in the vagina
reflect, to a considerable extent, the changes that are taking
place in the uterus.
F o r this research, Dierks used healthy vaginal mucosa
excised in connection with gynaecological operations. Dierks
does not state from what portion or portions of the vagina
his material was obtained. It was fixed in 10 per cent
formalin, washed in running water, embedded in gelatin after
the method of Gaskell-Graff, and cut with a freezing microtome. Iii a single case the paraffin method mas used. The
thickness of the sections was 8 p to 10 p. The sections used
f o r photographic illustrations were stained with haematoxylin
and eosin.
The material was obtained from thirty different women
of child-bearing age at varying periods of the menstrual
cycle. The following stages in the history of the vaginal
epithelium were described and illustrated :
1. First day after the beginning of menstruation in a
twenty-nine-year-old woman who had borne two children.
The section shows tlie well-known stratified squarnous epithelium of the vagina; the surface is covered with clumps
of red blood corpuscles wliich have come from the uterus.
2. Fourth day after tlie beginning of menstruation. From
a thirty-eight-year-old woman who had borne four children.
The sections show, in general, the same appearance as the
preceding.
3. Seventh day after the onset of menstruation. From a
forty-three-year-old woman ~ 7 h ohad borne three children.
‘Ein gaiiz anderes Rild’: in contrast with the preceding
preparations, the epithelium shows a three-layered condition.
The most superficial layer ( ‘Funktionalis, Regenerationsoder Wechselschicht ’), next t o the vaginal lumen, consists of
two or three rows of cells and shows less intense affinity f o r
the stains. I n general, this layer appears glassy and swollen;
its cells are thicker than the cells of the second or middle
layer. The second layer (‘intra-epitheliale Verhornungszone’) consists of four or five rows of intensively stained
320
BEILTR.IM G . SMITH
cells which show the beginning of cornification. Here the
individual cells are extraordinarily flattened ; the nuclei are
strongly shrunken and in some places a r e scarcely visible.
The condition of the basal layer (‘Rasalis’) is practically
the same as in the corresponding region of the preceding
stage.
4. Ten days after tlie beginning of menstruation. The
material comes from a thirty-seven-year-old Tvt’ornan who had
horne one child. The superficial layer has increased in thicliness; it consists of five to seven rows of cells. With the
adrance toward tlie premenstrual stage, this laper increases
in height. The layer of cells undergoing cornification is
slightly thicker than in the preceding stage. The basal layer
is nnchangecl.
5. Sixteen days after the heginning of menstruation (and
according t o Dierlts, about the time of ovulation). From a
thirty-1hree-year-old primipara. The superficial layer consists of from nine to eleven rows of cells, and the outlines of
the individual cells are more distinct than in the preceding
stage. The other layers show no appreciable change.
6. Twentp-tmo days after the beginning of menstrnation,
and therefore in an early premenstrual stage. The material
w-as obtained from a thirty-seven-year-old woman who had
horne four children. In this stage tlie division into three
layers is especially marked. The superficial layer has increased in lieiglit aiitl consists of thirty to thirty-four rows
of cells which are in a karyopycnotic arid chromatolytic condition preparatory t o desquamation.
7. Immediately after menstruation. The material was
taken from a thirty-three-year-old woman who had borne
two children. Both superficial and horny layers of the preceding stage have been cast off, and the basal layer now
constitutes the entire epithelium. The fullness of the capillaries of the endometrium is especially noteworthy. During
the premenstruum there is a gradually increasing hyperaemia
of the endometrium, which reaches its high point during the
menstrual bleeding.
EPITHELIUM O F THE HUMAN VAGINA
321
I n his discussion Dierks emphasizes the importance of the
superficial zone, which he terms ‘ein besonderes Differenzierungsprodukt des Epithels.’
I n a severe case of toxic pseudomenstruation, described by
Dierks, the vaginal mucosa showed the same condition as in
normal menstruation.
Adler (’28) stresses the importance of obtaining material
from the same general region of the vagina; all his material
was taken from the dorsal wall, between the anterior and
middle thirds. His material was obtained in part through
gynaecological operations, in part by the method of biopsy,
and fixed in 10 per cent formalin. I n most cases it m7as embedded in paraffin; in a single case celloidin mis used.
Several staining methods, including haematoxyliii and eosin,
were employed.
Considerable variation in the height of the vaginal epithelium was found, both in different persons and in different
parts of a single preparation. With respect to the peculiar
differentiation of the vaginal epithelium into zones o r layers,
the results of this study confirm, in general, those of Dierks ;
but as might be expected, the condition of the epithelium was
not precisely alike in different individuals on the same day
of the menstrual cycle.
MATERIAL AND METIIODS
The present study is based primarily upon the material
obtained from a single individual, an unmarried girl aged
twenty-three years, who died suddenly from encephalitis.
She became acutely ill during the afternoon, was talren to a
hospital at 7 P.M., and died at 10 o’clock the next morning.
The autopsy disclosed no haemorrhage except in the uterus.
The vagina, uterus, uterine tubes, and ovaries were removed
a t autopsy one hour after death and fixed in formalin.
Practically all this material was immediately cut into
pieces of a size suitable for sectioning for class use, and a
few weeks later these pieces were embedded in paraffin.
Though the material was obtained iii November, 1926, its
value for pu~posesof investigation mas not appreciated until
it was sectioned more than two years later ; consequently,
tlicl precise location of 1)ieces removed f o r sectioning was
not, recorded a s fully as might be desired. The sections mere
cut 10 I.I thick and were stained in haematoxylin and eosin.
l n most cases the sections from each block were numbered in
serial order.
For comparison, a11 araila1)lc 111iinaii material was utilized,
hut iioiic of this proved of value f o r the present study save
tlie vagina of a thirtyyear-old nullipara, cat in paraffin and
stainctl iii haematoxyliii and eosin. Scctions of the vagina
from four other iudiritlnals mere examined, but these were
eithcr pathological or did not come within the cliilcl-bearing
age.
The drawing reproduced in figure 1 was made ~ 7 i t hthe aid
of‘ a camera lncida. The photomicrographs reproduced in
figures 3 t o 6 (pl. 1) were made imtlcr the direction of the
aut lior by Rlr. Alvin Taylor ; all the other photomicrographs
a r e tlie work of RTr. hlartin Haggett.
ORSEIZVATIONS
7’0 facilitate compai.isoii in the event that xdditioiial material is d e s c d d later, the following records of otwxvations
are grouped according to cases. The case number designates
all the material obtained from a siiigle individual.
Case 1
Case 1 comprises the organs obt ainetl in November, 192G,
from a nulliparous female aged twenty-three years. All the
illustratioiis a r e based on this material.
I’a,qi+ia. Tlie mall of the vagina was cut into twenty-five
i*ectangular segments which collectively represent the entire
organ, save that numerous small aiid irregular pieces from
various parts of the vagina. were discarded. Unfortunately,
the location of each of the twenty-fire pieces with respect t o
the organ as a whole was not recorded.
EPITHELIIJM O F THE H U M A N VAGINA
323
All of these segments mere embedded in paraffin, and at
least a dozen sections were cut from each and examined
under the microscope. With respect to the division of the
epithelium into zones or layers such as a r e described by
Dierks, the condition found in different blocks varied widely.
Four lolocks showed only ordinary stratified sqnamous epithelium. I n thirteen blocks the division of the epithelium into
zones or layers was indicated lout slightly. In four blocks
the tliree zones were moderately differentiated. I n the four
Fig. 1 Drawing of a transverse section tliroug?i the vaginal miico~a of a
tffenty-three-year-oId nnllipara, sliowiiig a portion of the epithelium orerlying
the summit of a papilla. T h c qitliclium is diff'erentiated into three z m c s or
1:iyers as follows : A , superficial zone; B , intra-epithelial zone of cornification;
C, basal zone. X 540. Early premenstrual stage.
remaining blocks all three zones were strongly differentiated,
as i n the early premenstrual stages described by Dierks.
These various conditions a r e represented photographically
in figures 3 to 16. The photographs shoiild be compared with
the drawing, figure 1, in which the zones a r e labeled.
I n some of those blocks in which the layers a r e slightly
differentiated, the zone of cornification is represented, either
wholly or in part, by a layer of slightly expanded pale cells
(figs. 3, 8, and 1 2 ) . This is a condition which seems to precede cornification. Even in those blocks that show the divi-
324
BERTRSM G. SMITH
sion into zones at its best, the condition is not uniform. I n
two of these blocks entirely converted into sections, more
than 200 from each block, all show a n cpithelium differentiatcd into three zones, but the degree of differentiation varies
widely. The zone of cornification is usually best developed
in the regions overlying the larger papillae (figs. 4, 9, and
14). I n a given section thc zone of cornification is often
interrupted a t intervals by a zone of slightly expanded cells
xvliich appear pale even by comparison with the peripheral
layw (figs. 4 and 9). I n places where the zone of cornifieation is well developed, a narrow pale zone sometimes underlies it (figs. 1 and 14). The cells uiiclergoiiig coriiificatioii ;LIT
greatly flattened and have pycnotic nuclei. Intermediate conditions a r e represented by slightly flattened cells ; their nuclei
stain deeply with haematoxylin.
The tunica propria is unusually rich in dilated capillaries
and the venules of the submucosa are moderately distended,
indicating a moderate hyperaemia. Otherwise there is
nothing to suggest a pathological condition. Very little
lymphoid tissue occurs in the tunica propria, and no leucocytes were found invading the epithelium.
Uterus. Transverse sections through the uterine mucosa
and including a portion of the mpometrium were cut from
several different blocks taken from the fundus of the uterus.
The general appearance of the uterine mucosa is shown in
figures 17 and 18.
The stage of the menstrual cycle represented by this uterus
was determined by comparison with the figures and descriptions of Eden and Lockyer ('28) and O'Leary ( '29). The
uterine glands were found to be in a condition characteristic
of the beginning of the premenstrual stage, reckoned as
twenty days after the beginning of the preceding menstruation, or eight days before the beginning of the next menstrual
flow. The lumina of the tubular glands are slightly enlarged
and the outlines of these glands a r e slightly sinuons-the
beginning of the sacculation characteristic of the menstrual
stage. The nuclei of the glandnlar cells have migrated
EPITHELIUM O F THE HUMAN VBGINA
325
slightly from their original positions at the basal ends of
the cells to positions that are nearly central but still slightly
nearer the basement membrane. There is some evidence of
secretory activity in the distal portions of the cytosomes of
these cells. There is a slight enlargement of the connectivetissue cells of the distal third of the tunica propria; this is
the beginning of the process of differentiation leading to the
distinction between peripheral compact a i d basal spongy
layers of the later premenstrual stages. There is considerable desquamation of the superficial epithelium and some
slight fragmentation of adjoining portions of the tunica
propria. The liaemorrhage is more profuse than would be
expected t o occur in an early premenstrual stage, but this
may represent a toxic pseudomeiistruatioii brought about
suddenly by the same agents that caused death. The larger
blood vessels of the eiidometrium are not enlarged and congested t o the extent one would expect in actual menstruation
or in a severe case of toxic pseudomenstruation such as is
described by Dierks ( '27).
Probably the best criteria of the stage of the menstrual
cycle represented by this uterus are furiiished by the condition of the glands and the connective-tissue cells of the tunica
propria. Distention of the capillaries, producing haemorrhage, is a change that might be brought about suddenly by
toxic influences ; but acceleration of the normal histological
and cytological changes in the glands and connective-tissue
cells would hardly be expected t o occur so readily in rcspoase to these influences. Judging from the coiidition of
the glands and the connective-tissue cells, this uterus is in
a very early premenstrual stage.
Gtcriizr t d i c s . From one of the uterine tubes transverse
sections were cut at various levels. A few observations on
some sections taken in the region of transition between the
inf unclihulum and the ampulla will suffice.
Venules and capillaries are well distended, indicating a
moderate hyperaemia. The lumen of the tube contains many
blood cells, presumably derived from the ovary; also very
326
REILTlL4M G. SMITH
iiiimcroiis smaller hornogeneous spherulcs of prohlcmatical
origin. The epithelium conforms very nearly to the figure
and description in Xcliaf€er (’20, fig. 532 and p. 439). It is
nsnally simple low columnar, hut in places it is two-rowed
psendostratified and more rarely it appears two-layered, due
to tlie extrusion of some of the cells from contact with tlie
1)asemeiit memhrane. Thus in its entirety the epithelium
does not conform to any single molyliological type. F o r an
epitheliiim that is always low, the diversity in the characteristics of the cells is indeed rerriarkahle. The basal cells are
of Tarions sizes and a r e usually ratlier pale, with vesicular
iinch~i. ‘Plie columiiar cells vary from large pale cuhoidal
colls with vesicular nuclei to slender deeply staining column a r cells ~ ~ i t pycnotic
li
nuclei. Somewhat rarely, wedgeshaped cells with pycnotic nuclei and scanty cytoplasm are
apparently being extritdcd from the epithelium into the lumen
of the tube, a s tlescribcd aiicl figured by Xobottn (’20, ])I. 41,
fig. 4 and Iegciid). Ciliated columiiar cells occui- singly and
in patches between wliich a r e considerable areas in xvliicli
cilia are absent. The cilia of individual cells are sometimes
clumped. The large pale cu1)oidal cells a r e usually ciliated.
Some of llie mocleratcly slender colnmnar cells are perhaps
secretory, since their distal w-alls bulge outmard am1 sphrrixles
similar to those foiintl free in the lumen of the tube appear
011 their exposed surfaces.
The cytoplasm of the coliimiiar
cells is stained in varyiiig degrees, but I have bcen uiiahle
to find secmtorp granules. Tf a n y of the cells of this region
arc secretory, there is n o sharp distinction between tlicm
and the ciliated cells, since some of the latter cells stain
tlceply and exhibit the same evidences of secretion found in
lion-ciliated cells.
0 varies. Each o r a r y was cut into thick transverse slices
p i ~ p a r a t o r yto embedding. All tlie sections were cut in a
~ ~ l a l transverse
ic
to the long axis of the ovary.
A l p records state that one of the ovaries gave superficial
indications of a recent ovulation. This probably refers to
tlie follicle contained i n two l~lockslabeled ‘early corpus
327
EPITIIELIUM O F THE HUMAN T‘AGIXA
luteum. ’ A representative section through this very early
corpus luteum is portrayed in figure 2. The lutein cells, best
developed on the side of the follicle shown in the lower part
of the figure, appear to be developed entirely from cells of
the tunica interna of the theca folliculi.
Another block was labelccl simply ‘corpus 1uteiim.’ This
block was completely sectioned and a corpus luteam foiind in
an advanced stage of development ; its corpus 1iaemorr.liagicum is almost entirely resorbed. Several other blocks lalwled
simply ‘ovary’ were sectioned and revealed nothing of particular intcrcst in this connection ; they contained the usual
assortment of follicles in various st ages of developmcnt,
Fig. 2 Photograph of a transverse section of the ornrv of
gear-old nullipaia, showing a very early corpus lutcuni. x fi.
R
twenty-tlirce-
atretic follicles, and corpora albicantia. The general appearance is that characteristic of a liealtliy ovary of a young
woman. Although the veiiis of tliesc ovaries are distended
with blood, this condition is probably iiormal for the stage
immediately following ovulation.
Case 2
Vagiiza o d y . This vagina is from a woman aged thirty
years, nulliparous. Tlic material consisted of four different
pieces of the vaginal wall embedded in parafin; it is not
known from what p a r t of the organ these pieces were obtained. Portions of each l)locl; were sectioned.
328
UERTGAM G. SNITH
I n most of tliis material the epithelium is cast into strong
folds or ridges, such as occur normally on the inner slurface
of the vagina. I n the more exposed situations the epithelium
ih
deeply eroded or desquamated. n’herever infoldiiig
omirs, the epithelium sliows as its typical condition a thick
hasal zone surmounted hy n very thin peripheral zone of
cornified cvAls wliicli appear t o be undergoing desqnamatioii.
-It tlie f ree snrface of‘ the epitlielinm a €el\- erytlirocytes were
found. The cells of the basal zone immediately iiiiclerlying
the coriiified cells are pale arid swollen. T n some few localities all tliwe zones are present. J n such places the cells of
the snperficial zone are r c r y larqc and swollen, with pyciiotic
~iuclciancl vacuolatetl cytoplasm ; these cells appear t o he
undergoing- degeneration a i d desqnamalioii. R? examining
regions wlierc the two-zoned axid three-zoned coiiditioiis exist
side by side, the zone of coriiified cells is found to he continuous. Thus the three-layered conditioii indicates a delayed
clesquamation. None of the stages described by Dierlrs presents precisely this condition of the epithelium, bnt it fits
readily into his series as a very late premenstrual stage.
A striking peculiarity of this vagina is tlie marlred distentioil of the veiiules of the submucosa ; evidently, tliere is
a pr*onou~iccdIi?per;mnia. As compared with case 1 there
is also a marlrecl inci.easc iii the number of leucocptes in tlie
t iinica propria, and there are iiumerous leiicocytes scattered
tlirougli the pcriplicral portions of tlic suhmucosa. I11 Imth
1 a y x s the distribution of leucocytes is irregular, with an
almost complete absence in many localities. Leucoc;r-tes are
most abunclanl in the tunica propria of tlie papillae. In
manly places, particularly above the papillae, tliere is a slight
iiifiltratiori of leucocptes into tlie deeper layers of the epit helium, arid occasionally leucocytes reach the free surf ace.
There is 110 evidence of pathological conditions in this vagina,
unless the ahundance of leucocytes be regarded as patho1ogical .
EPITHELIUM O F T H E HUMAX VAGINA
329
DTSCUSSlOR
The demonstration of histological and cytological changes,
correlated with the menstrual cycle, in the epithelium of the
human vagina is not surprising, in view of the results previously obtained through the study of the oestroiis cycle in
other animals. I n the mouse Morau ('89) found that on the
fifteenth day postpartum a layer of cornified cells was beginning to form under the superficial layer of the stratified
vaginal mucosa. I n non-pregnant guinea-pigs Retterer ( '92)
observed that regular changes, involving the formation of a
layer of cornified cells, occurred in the vaginal epithelium.
For the study of the oestrous cycle in animals, a new techdevised by
nique-the
method of vaginal smears-was
Stockard and Papanicolaou ( '17). I n their researches on
the guinea-pig, the cellular content of the vaginal fluid was
used as an indicator of the phase of the oestrous cycle. I n
this connection the histological strncture of the wall of the
vagina was examined, and a peculiar stratification, f ollomed
by extensive desquamation, was found to occur a t certain
phases of the cycle. Farther ohservatioiis on the histological
changes in the vaginal mucosa have been made in the guineapig (Selle, '22), the mouse (Allen, '22), rat (Long and Evans,
'22), the opossnm (Hartman, ' 2 3 ) , and the sow (Wilson, '26).
I n all these animals there are cyclical changes in the vaginal
epithelium comparable to those that occur in the human
vagina. I n the guinea-pig, mouse, and rat the intra-epithelial
zone of cornification is sharply differentiated a t a certain
stage of the oestrons cycle.
I n the guinea-pig, mouse, rat, etc., following the stage of
desquamatioii, vast numbers of leucocytes infiltrate through
the epithelium into the lumen of the vagina. This migration
of leucocytes appears to be a reaction to the presence of the
desquamated cells, and the function of these leucoeytes is the
digestion of these superfluous cells. A similar course of
events in the human vagina is probable, but published observations of a conclusive nature are lacking. The infiltration
of leucocytes into the epithelium of the vagina described in
T H E ANATOMICAI. IIECORD,
VOL. 43, NO. 4
330
B E R T R A M G. SMITH
this paper uiidcr case 2 is suggestive, but in the absence of
a clinical history one caniiot he sure that the coriditioii is not
patliological.
Aside from tlie confirmatioil of results previously obtained
‘by others, the ontstanding feature of the present paper is the
domonstratioii of great variatioii in the condition of tlic epitliclhim i n differeiit parts of the all of the human vagina
(luring tlie early premenstrual stage, which, according to
Ilierks, is the time when difiertliitiation of tlie epithelium
reaches its height. This variation may indicate one of two
things: a ) tliat some portions of the vaginal epithelium d o
riot undergo the cyclical changes that a r e so proiiounced in
other portions, or, I?) that tlie clianges proceed at different
rates in different parts of the vagina. h search of the literature docs not help 11s mixcli in answering Chis question. Dierlrs
(’27) does not tell from what portion or portions of the
hnman vagina liis material x7as obtained. Adler (’38) states
that his material was obtained from one locality only: the
dorsal wall I)ctmeen the anterior and middle thirds. h i the
guinea-pig Selle ( ’22) states that tlie coriiifying process
Iwgins rather suddenly and continues at a rapid rate simult a i i e o i ~ l ythrongliout the eiitirc vagina, and Kelly ( ’39) asserts that “tlio structure was almost uniformly the same
from one end of the organ to the other.”
In the present state of our linowledge of tlie hnman
nt criiic tubes, the o(wriwice of histological and cytological
changes in tlicir epithelium, correlated with the menstrual
cycalc, is problematical. In the mouse, according to Allen
( ‘ti), the oviducts exhibit definite cpcilical changes. I n tlic
ciliated portions of the ovidnct, near tlie periovariaii sac,
some of llie nuclei of epithelial cells are extruded during the
metoestrum aiicl come to lie on tlie free surface of the epithelium. The process is of degeiicmtive significance. In the
humaii uterine tubes clescribed in the present paper, I have
iioted entire cells apparently i i i process of being estrutled
f r o m the cpitliclium into the lunieil of the tube. Tliis occurred during an e a d y premenstrual stage, hiit in the al~scnce
EPITHELIUM O F T H E HUMAN VAGINA
331
of timed material f o r comparison no coiiclusion can be drawn
from this observation.
SUMMARY
1. All the internal genital organs of a twenty-three-yearold nullipara (case 1) were obtained and preserved one hour
after death which followed a very brief illness.
2. The stage of the menstrual cycle was determined by the
study of sections of the uterine mucosa. The stage indicated
is a very early premenstrual stage. Confirmatory evidence
is afforded by the presence of a corpus lnteum in a very
early stage of development.
3. Practically all parts of the wall of the vagina were
studied in transverse sections. The condition of the epithelium varies from ordinary stratified squamous epithelium to
an epithelium differentiated into t h e e zones or layers, the
middle zoiic consisting of cells undergoing cornificat’1011.
4. L4notlier vagina (case 2 ) showed a similar condition of
the epithelium, save that the outer layers were in process of
desquamation, aiid infiltration of leucocytes had occurred.
5. Comparison is made with the cyclical changes known to
occur in the vagiiial epithelium of certain animals, eg., the
guinea-pig, mousc, rat, ctc.
6. The condition of the epithelium of the uterine tubes in
case 1 is described and the possibility of cyclical changes in
this region discussed.
BIBLIOGRAPHY
ADLER, KARL 1828 Die Verandriungen des Rclieidciiepitliels wahrend dcs
Menstruntionsqklus und dei Gcstntionsperiodc. Arcliiv fur Gynakologie, Bd. 134, 8. 504-518.
ALLEN, EDGAR1822 The oestrous cyclc in the mouse. Am. Jour. Anat., vol. 30,
pp. 297-371.
DIERKS,KLAAS 1927 Der norniale meiisuelle Zyklus drr menscliliclren Vagimlschleimhaut. A4rchi~r.f u r GjnEkologie, Bd. 130, S. 46-59.
EDEN,TIIOMASW A w s , AND LOCKYER,
CUTHRERT 1928 Gjnaecology, 3rd ed.
London: The Maemillan Co.
HARTXIAX,
C ~ R LG. 1923 The oestrous cycle in t h e opossum. Am. J o u r . Anat.,
vol. 32, pp. 333-421.
332
BERTRAM G. SMITH
Iir I.I,Y, G. 1,. 1939 The histological transformations in the vaginal epithelium
of the guinea pig. Am. J o u i . Anat., 1701. 43, pp. 247-287.
H. M. 1922 Tiir oestrous cycle in the r a t and its
LONG,I. A., AND EVANS,
associated phenomena. Memoirs of the University of California, no. 6.
31 OILAU, €I. 1889 Des trmsformations CpithCliales de kt niiiqueuse du vagin
d e qiielques longenis. Join-. de 1’Anat. et de la Ph>siol., pp. 273-287.
0 ’ L E ~ YJMES
,
LEF 1039 F o r m clianges in the human utermc glands during
the menstrual cycle a n d in early pregnancy. Am. Jour. Anat.,
VOI. 43, pp. 589-346.
I’AI’.1NICOLAOU, Gro. N.
1924 ‘rhe diagnosis of early human prc’gnanr?- by the
vaginal smear method. I’roc. Soc. Exp. Biol. and hfcd., 101. 22,
pp. 4 3 6 4 3 7 .
XmmcnEK, E. 1892 E\olution de 1’6pitli6lium ilu vagin.
(DeuxiBme note.)
Memoires Comptes Reridus Sociktt? de Biologic, Paris, T. 44, pp. 566568.
SCIIAFPEK,
JOSEF 1930 Vorlrsungen ubcr Histologic und IIistogenese. L e i p i g :
Wilhelni Engclmaun.
SLLLE,RAYMOND 51. 7922 Changes in the vagjnal epithelium of the guinea-pig
during the oestious c y l e . Am. Jour. Anat., vol. 30, pp. 4 2 0 4 4 9 .
SOBOTTA,
J. 1920 Atlas und Lelirbuch tier IIistologie und mikroskopisehe
Anatomie ties Mensellen. Dritte unveriinderte Anflage. Munclirm :
J. F. I~cliniann.
STOCKARD,
CHARLESR., A N D PAPANICOLAOU,
GEORGEN. 1917 The rxistence of
a typical oestrous cyclc in the guinea-pig, with a description of its
liistological and physiological cbangcs. Am. Joni. Anat.,
22,
11p. 225-283.
S z ~ ~ r o ~ o rz,n i L.
t
1921 Lt~lirlJucli der Histologie und der mikroskopische
Anatomie. Lcipzig: Curt Kabitzsch.
WILSON,K ~ R MILLER
L
1926 Ilistologicnl changcs in the vaginal ~niicosaof the
sow in relation t o the oestrous cyclc. ilni. Jour. h a t . , vol. 37,
pp. 417431.
1701.
PLATES
333
PLATE 1
BXPLANSTlOX O F FIGURLS
911 tlir figures are pliotogra~ilis of tranxversc sections througli tlie
miicnsa of 3 twenty tlirec )cnr-old niillipara. x 80.
T
:iginal
3 The intun-cpitlielinl zone of roinificntion is j u s t heginning to d l f l e i ~ i i t i : i t e
:11~1vethe larger papillae :mil is elsewlieie represented 1,s a 7 0 1 1 ~nf 1:rige 1mle
roJls.
4 The intr:~-epitlielial zonr of cornificntion is well deTeloptd above t h e
p:cpill:re and is clsrwlir~reniinglcd with a zone of large pale cells.
3 T h e intra-rpithelial zone of cornific:ition is well d r eloped
~
xnrl fornis n
continuous 1a)er. There is a n :ilmost entire absence of 1 : q c pale cells; tliis
(ondition is of c~xccptioii:rl ocrurrriire a n d is limited t o regions where pnpillac
:iir eithcr absent or a r c p w l y dc-c.rlopc~L
6 T’lie intra epithelial miic of rornific?tion is strongly developed, but contains
x fcn h r g e pale cells.
334
EPITHELIUM O F THE IIGMAN VAGINA
PLATE 1
BERTRAM G . SMITH
335
PLATE 2
EXPLANATION OF FIGURES
All the figures a r e photographs of trans7 erse sections through the vaginal
niucosa of a t~,enty-tliree-year-olanullipara. x SO.
7 and 8 The intra-epithelial zone of cornification is just beginning to form
arid is mingled with, or overlies, a narrow zone of large pale cells.
9 The intm-epithelial zone of cornifieation is strongly differentiated above
the large papilla and is elsewhere interrupted at intervals b y large pale cells.
1 0 The intra-epithelial zone of eornification is strongly differentiated, a n d in
one place, near tho left end of the figure, it is split in a plane parallel t o the
surface of the epithelium. A few large pale cells a r e present at intervals
throughout most of the zone of c,ornification.
336
PLATE 2
EPITHELIUM O F THE HUMAN VAGINA
BERTRAM 0. SMITH
337
PLATE 3
E W L 4NATlON OF FIGUEES
A l l tlie figiiws arc p1iotogr;iplis of tr:iiis\crse scetioiis through thc vaginal
niuiwsa of a twenty-tlirce-vear-old 1iullipar:i. x 200.
0rthn:ir;v OT unniodified stratified sciunmous epitlielium.
epithelium is of rather exceptional occurrence.
12 This figure coiiesponds to a portion of figurc 8.
13 This figure coiirsponds t o a portion of figure 7.
71
hucli
338
I n this laginn
PLATE 3
EPITHELIUM OF THE HTTNAN VAGINA
BERTR.431 (1.
SMITH
339
PLATE 4
EXPLANATION OF FIGURES
All the figures a r e photographs of transverse sections through the vaginal
mueosa of a twentv-thrce-4.e:ir-old nullipara. X 200.
14 This figure corresponds to a portion of figure 9.
15 and 16 The intra-epithelial zone of cornification is strongly differentiated.
A few large pale cells occur, either mingled with the zone of coruification or
situated along its borders.
340
EPITHELIUM OF THE HUMAN VAGINA
BEBTBAX a. SXITIE
PLATE 4
341
PLATE 5
EXPLANATIOZT OF FIGURES
1 7 arid 1s Photographs of transverse scctioiis through tlir uteriiic niueosa of
a twentv-tIirc,e-~exrold nullipam. x 80. This uterus a n d t h e vagina I rprcsented
in p1:ites 1 to 4 arc from t h e same individual
342
PLATE 5
EPITHELIUM O F TIIE HGMAN VAGINA
BERTRAM G . SMITH
343
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