Mons pubis

The mons pubis is the rounded hair-bearing area of skin over the pubic symphysis and adjacent pubic bone. It is formed by a mass of subcutaneous adipose connective tissue. Before puberty, the mons pubis is relatively flat and the labia minora are poorly formed. During adolescence, coarse hair forms over the mons and labia majora and the labia minora become more prominent and flap like. In adults, the mons is covered by coarse hair that is usually limited above by a horizontal boundary; in males there is a continuation of pubic hair to the umbilicus. After the menopause, pubic hair thins and labial tissue atrophies slightly.

Labia majora

The labia majora are two prominent, longitudinal folds of skin that extend back from the mons pubis to the perineum (Fig. 77.1B). They form the lateral boundaries of the vulva. Each labium has an external, pigmented surface covered with hairs and a smooth, pink internal surface with large sebaceous follicles. Between these surfaces there is loose connective and adipose tissue, intermixed with smooth muscle (resembling the scrotal dartos muscle), vessels, nerves and glands. The uterine round ligament may end in the adipose tissue and skin in the anterior part of the labium. A persistent processus vaginalis and congenital inguinal hernia may also reach a labium. The labia are thicker anteriorly, where they join to form the anterior commissure. Posteriorly they do not join, but instead merge into neighbouring skin, ending near and almost parallel to each other. The connecting skin between them posteriorly forms a ridge, the posterior commissure, that overlies the perineal body and is the posterior limit of the vulva. The distance between this and the anus is 2.5–3 cm thick and is termed the ‘gynaecological’ perineum.

Labia minora

The labia minora are two small cutaneous folds, devoid of fat, that lie between the labia majora. They extend from the clitoris obliquely down, laterally and back, flanking the vaginal orifice. Anteriorly, each labium minus bifurcates. The upper layer of each side passes above the clitoris to form a fold, the hood or prepuce, which overhangs the glans of the clitoris. The lower layer of each side passes below the clitoris to form the frenulum of the clitoris (Fig. 77.1A,C). Sebaceous follicles are numerous on the apposed labial surfaces. Sometimes an extra labial fold (labium tertium) is found on one or both sides between the labia minora and majora.

Vestibule

The vestibule is the cavity that lies between the labia minora. It contains the vaginal and external urethral orifices and the openings of the two greater vestibular (Bartholin’s) glands and of numerous mucous, lesser vestibular glands. There is a shallow vestibular fossa between the vaginal orifice and the frenulum of the labia minora.

Bulbs of the vestibule

The bulbs of the vestibule lie on each side of the vestibule. They are two elongated masses of erectile tissue, 3 cm long, which flank the vaginal orifice and unite anterior to it by a narrow commissura bulborum (pars intermedia). Their posterior ends are expanded and are in contact with the greater vestibular glands. Their anterior ends taper and are joined by a commissure and also to the clitoris by two slender bands of erectile tissue. Their deep surfaces contact the inferior aspect of the urogenital diaphragm, and superficially each is covered by bulbospongiosus posteriorly (Fig. 77.2A–C).

Fig. 77.2 A, Muscles of the vestibule and clitoris. B, Erectile tissues of the clitoris. C, Erectile tissues of clitoris, vestibule and greater vestibular gland with a surface anatomy overlay.

(A, B adapted from Drake, Vogl and Mitchell 2005. C from Drake, Vogl and Mitchell 2005.)

Clitoris

The clitoris is an erectile structure partially enclosed by the anterior bifurcated ends of the labia minora. It has a root, a body, and a glans. The body can be palpated through the skin. It contains two corpora cavernosa, composed of erectile tissue and enclosed in dense fibrous tissue, and separated medially by an incomplete fibrous pectiniform septum. The fibrous tissue forms a suspensory ligament that is attached superiorly to the pubic symphysis. Each corpus cavernosum is attached to its ischiopubic ramus by a crus that extends from the root of the clitoris. The glans clitoris is a small round tubercle of spongy erectile tissue at the end of the body and connected to the bulbs of the vestibule by thin bands of erectile tissue. It is exposed between the anterior ends of the labia minora. Its epithelium has high cutaneous sensitivity, important in sexual responses (Fig. 77.2).

Vascular supply and lymphatic drainage of the vulva

Arteries

The arterial blood supply of the female external genitalia is derived from the superficial and deep external pudendal branches of the femoral artery and the internal pudendal artery on each side (Fig. 77.3A).

Fig. 77.3 Vessels (A), nerves and lymphatics (B) of the female pelvis. Sagittal view.

(From Sobotta 2006.)

Innervation

The innervation to the lower genital tract is shown in Fig. 77.5 and Table 77.1.

Fig. 77.5 Innervation of the female reproductive system.

(From Sobotta 2006.)

The sensory innervation of the anterior and posterior parts of the labium majus differ. The anterior third of the labium majus is supplied by the ilioinguinal nerve (L1), the posterior two-thirds are supplied by the labial branches of the perineal nerve (S3), and the lateral aspect is also innervated by the perineal branch of the posterior cutaneous nerve of the thigh (S2).

Vascular supply and lymphatic drainage

Innervation

The lower vagina is supplied by the pudendal nerve (S2, S3 and S4). The upper vagina is supplied by the splanchnic nerves (S2, S3 and sometimes S4).

Microstructure

The vagina has an inner mucosal and an external muscular layer. The mucosa adheres firmly to the muscular layer. There are two median longitudinal ridges on its epithelial surface, one anterior and the other posterior. Numerous transverse bilateral rugae extend from these vaginal columns. They are divided by sulci of variable depth, giving an appearance of conical papillae, which are most numerous on the posterior wall and near the orifice, and which are especially well developed before parturition. The epithelium is non-keratinized, stratified, squamous similar to, and continuous with, that of the ectocervix. After puberty it thickens and its superficial cells accumulate glycogen, which gives them a clear appearance in histological preparations.

Fig. 77.4 Muscles, vessels and nerves of the female perineum. Inferior view.

(From Sobotta 2006.)

The vaginal epithelium does not change markedly during the menstrual cycle, but its glycogen content increases after ovulation and then diminishes towards the end of the cycle. Natural vaginal bacteria, particularly Lactobacillus acidophilus, break down glycogen in the desquamated cellular debris to lactic acid. This produces a highly acidic (pH 3) environment, which inhibits the growth of most other microorganisms. The amount of glycogen is less before puberty and after the menopause, when vaginal infections are more common. There are no mucous glands, but a fluid transudate from the lamina propria and mucus from the cervical glands lubricate the vagina (Fig. 77.8). The muscular layers are composed of smooth muscle and consist of a thick outer longitudinal and an inner circular layer. The two layers are not distinct but connected by oblique interlacing fibres. Longitudinal fibres are continuous with the superficial muscle fibres of the uterus. Half way along the vagina is a U-shaped muscular sling, called the pubo-vaginalis. The lower vagina is also surrounded by the skeletal muscle fibres of bulbospongiosus. A layer of loose connective tissue, containing extensive vascular plexuses, surrounds the muscle layers.

Fig. 77.8 Stratified squamous non-keratinizing epithelium (E) covering the ectocervix and vagina. The cells of the middle and upper layers appear clear due to their content of glycogen.

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

Body

The body of the uterus is pear shaped and extends from the fundus superiorly to the cervix inferiorly. Near its upper end, the uterine tubes enter the uterus on both sides at the uterine cornua. Inferoanterior to each cornu is the round ligament and inferoposterior is the ovarian ligament. The dome-like fundus is superior to the entry points of the uterine tubes and covered by peritoneum which is continuous with that of neighbouring surfaces. The fundus is in contact with coils of small intestine and occasionally by distended sigmoid colon. The lateral margins of the body are convex, and on each side their peritoneum is reflected laterally to form the broad ligament, which extends as a flat sheet to the pelvic wall (Fig. 77.13). The anterior surface of the uterine body is covered by peritoneum which is reflected onto the bladder at the uterovesical fold (Fig. 77.14). This normally occurs at the level of the internal os, the most inferior margin of the body of the uterus. The vesico-uterine pouch between the bladder and uterus is obliterated when the bladder is distended, but may be occupied by small intestine when the bladder is empty. The posterior surface of the uterus is convex transversely. Its peritoneal covering continues down to the cervix and upper vagina and is then reflected back to the rectum along the surface of the recto-uterine pouch (of Douglas), which lies posterior to the uterus (Fig. 77.15). The sigmoid colon and occasionally the terminal ileum lie posterior to the uterus.

Fig. 77.13 Laparoscopic view of the broad ligament.

Fig. 77.14 Laparoscopic view of the anterior part of the pelvis showing uterovesical fold anterior to the uterus.

Fig. 77.15 Laparoscopic view of the posterior pelvis showing the pouch of Douglas (recto-uterine pouch) with the sigmoid colon descending towards the rectum.

The cavity of the uterine body usually measures 6 cm from the external os of the cervix to the wall of the fundus and is flat in its anteroposterior plane. In coronal section, it is triangular, broad above where the two uterine tubes join the uterus, and narrow below at the internal os of the cervix (Fig. 77.16).

Fig. 77.16 Hysteroscopic view of the endometrial cavity of the uterus.

There may be failure in fusion of the paramesonephric (Müllerian) ducts, which results in a uterus that is not pear shaped. There may just be a septum (septate uterus) or partial clefting of the uterus (bicornuate uterus); the most extreme example is a septate vagina, two cervices, and two discrete uteri, each with one uterine tube (uterus didelphys).

Cervix

The adult, non-pregnant cervix is narrower and more cylindrical than the body of the uterus and is typically 2.5 cm long. The upper end communicates with the uterine body via the internal os and the lower end opens into the vagina at the external os. In nulliparous women, the external os is usually a circular aperture, whereas after childbirth it is a transverse slit. Two longitudinal ridges, one each on its anterior and posterior walls, give off small oblique palmate folds that ascend laterally like the branches of a tree (arbor vitae uteri): the folds on opposing walls interdigitate to close the canal. The narrower isthmus forms the upper third of the cervix. Although unaffected in the first month of pregnancy, it is gradually taken up into the uterine body during the second month to form the ‘lower uterine segment’ (see below). In non-pregnant women the isthmus undergoes menstrual changes, although these are less pronounced than those occurring in the uterine body. The external end of the cervix enters the upper end of the vagina, thereby dividing the cervix into supravaginal and vaginal parts. The supravaginal part is separated anteriorly from the bladder by cellular connective tissue, the parametrium, which also passes to the sides of the cervix and laterally between the two layers of the broad ligaments.

Pelvic ligaments and peritoneal folds

The uterus is connected to a number of ‘ligaments’. Some are true ligaments in that they have a fibrous composition and provide support to the uterus, some provide no support to the uterus, and others are simply folds of peritoneum.

Peritoneal folds

The parietal peritoneum is reflected over the upper genital tract to produce anterior (uterovesical), posterior (rectovaginal) and lateral peritoneal folds. The lateral folds are commonly called the broad ligaments.

Uterovesical and rectovaginal folds

The anterior or uterovesical fold consists of peritoneum reflected onto the bladder from the uterus at the junction of its cervix and body. The posterior or rectovaginal fold consists of peritoneum reflected from the posterior vaginal fornix on to the front of the rectum, thereby create the deep recto-uterine pouch of Douglas. The pouch of Douglas is bounded anteriorly by the uterus, supravaginal cervix and posterior vaginal fornix, posteriorly by the rectum and laterally by the uterosacral ligaments.

Broad ligament

The lateral folds or broad ligaments extend on each side from the uterus to the lateral pelvic walls, where they become continuous with the peritoneum covering those walls (Figs 77.17, 77.18). The upper border is free and the lower border is continuous with the peritoneum over the bladder, rectum and pelvic side-wall. The borders are continuous with each other at the free edge via the uterine fundus and diverge below near the superior surfaces of levatores ani. A uterine tube lies in the upper free border on either side. The broad ligament is divided into an upper mesosalpinx, a posterior mesovarium and an inferior mesometrium.

Fig. 77.17 Pelvic peritoneal reflections, demonstrating the broad ligament and its contents.

(From Drake, Vogl and Mitchell 2005.)

Fig. 77.18 Ovaries and broad ligament, superior view with the uterus lifted away from the bladder.

(From Sobotta 2006.)

Mesosalpinx

The mesosalpinx is attached above to the uterine tube and posteroinferiorly to the mesovarium. Superior and laterally it is attached to the suspensory ligament of the ovary and medially it is attached to the ovarian ligament. The fimbria of the tubal infundibulum projects from its free lateral end. Between the ovary and uterine tube the mesosalpinx contains vascular anastomoses between the uterine and ovarian vessels, the epoophoron, and the paroophoron (Fig. 77.19). The mesovarium projects from the posterior aspect of the broad ligament, of which it is the smaller part. It is attached to the hilum of the ovary and carries vessels and nerves to the ovary.

Fig. 77.19 Broad ligament (left) and blood supply to the uterus and ovaries (right).

(From Drake, Vogl, Mitchell, Tibbitts and Richardson 2008.)

Mesometrium

The mesometrium is the largest part of the broad ligament, and extends from the pelvic floor to the ovarian ligament and uterine body. The uterine artery passes between its two peritoneal layers typically 1.5 cm lateral to the cervix: it crosses the ureter shortly after its origin from the internal iliac artery and gives off a branch that passes superiorly to the uterine tube, where it anastomoses with the ovarian artery (Fig. 77.19). Between the pyramid formed by the infundibulum of the tube, the upper pole of the ovary, and the lateral pelvic wall, the mesometrium contains the ovarian vessels and nerves lying within the fibrous suspensory ligament of the ovary (infundibulopelvic ligament). This ligament continues laterally over the external iliac vessels as a distinct fold. The mesometrium also encloses the proximal part of the round ligament of the uterus, as well as smooth muscle and loose connective tissue.

Ligaments of the pelvis

The ligaments of the pelvis consist of the round, uterosacral, transverse cervical and pubocervical ligaments.

Uterosacral, transverse cervical and pubocervical ligaments

The uterosacral ligaments are recto-uterine folds and contain fibrous tissue and smooth muscle (Fig. 77.18). They pass back from the cervix and uterine body on both sides of the rectum, and they are attached to the front of the sacrum. The ligaments can be palpated laterally on rectal examination. On vaginal examination they can be felt as thick bands of tissue passing downwards on both sides of the posterior fornix. The transverse cervical ligaments (cardinal ligaments, ligaments of Mackenrodt) (Fig. 77.20) extend from the side of the cervix and lateral fornix of the vagina to attach extensively on the pelvic wall. At the level of the cervix, some fibres interdigitate with fibres of the uterosacral ligaments. They are continuous with the fibrous tissue around the lower parts of the ureters and pelvic blood vessels. Fibres of the pubocervical ligament pass forward from the anterior aspect of the cervix and upper vagina to diverge around the urethra (Fig. 77.20). These fibres attach to the posterior aspect of the pubic bones.

Fig. 77.20 Supporting ligaments of the pelvis showing the transverse cervical ligaments.

(From Sobotta 2006.)

While the uterosacral and transverse cervical ligaments may act in varying measure as mechanical supports of the uterus, levatores ani and coccygei, the urogenital diaphragm and the perineal body appear at least as important in this respect. There has been renewed interest in the supporting structures of the pelvis, and the subject has been reviewed in detail by Delancey (2000).

Vascular supply and lymphatic drainage

Arteries

The arterial supply to the uterus comes from the uterine artery (Fig. 77.21). This arises as a branch of the anterior division of the internal iliac artery. From its origin, the uterine artery crosses the ureter anteriorly in the broad ligament before branching as it reaches the uterus at the level of the cervico-uterine junction. One major branch ascends the uterus tortuously within the broad ligament until it reaches the region of the ovarian hilum, where it anastomoses with branches of the ovarian artery. Another branch descends to supply the cervix and anastomoses with branches of the vaginal artery to form two median longitudinal vessels, the azygos arteries of the vagina, which descend anterior and posterior to the vagina. Although there are anastomoses with the ovarian and vaginal arteries, the dominance of the uterine artery is indicated by its marked hypertrophy during pregnancy.

Fig. 77.21 A, Normal arterial supply to uterus, uterine tubes and ovaries. B–F, Variant arterial supply.

(From Sobotta 2006.)

The tortuosity of the vessels as they ascend in the broad ligaments is repeated in their branches within the uterine wall. Each uterine artery gives off numerous branches. These enter the uterine wall, divide and run circumferentially as groups of anterior and posterior arcuate arteries. They ramify and narrow as they approach the anterior and posterior midline so that no large vessels are present in these regions. However, the left and right arterial trees anastomose across the midline and unilateral ligation can be performed without serious effects. Terminal branches in the uterine muscle are tortuous and are called helical arterioles. They provide a series of dense capillary plexuses in the myometrium and endometrium. From the arcuate arteries many helical arteriolar rami pass into the endometrium. Their detailed appearance changes during the menstrual cycle. In the proliferative phase helical arterioles are less prominent, whereas they grow in length and calibre, becoming even more tortuous in the secretory phase.

Veins

The uterine veins extend laterally in the broad ligaments, running adjacent to the arteries and passing over the ureters. They drain into the internal iliac veins (see Fig. 77.30). The uterine venous plexus anastomoses with the vaginal and ovarian venous plexuses.

Fig. 77.30 Broad ligament dissected and pelvic lymph nodes removed to reveal structures of the right-hand pelvic sidewall.

Innervation

The nerve supply to the uterus is predominantly from the inferior hypogastric plexus. Some branches ascend with, or near, the uterine arteries in the broad ligament. They supply the uterine body and tubes, and connect with tubal nerves from the inferior hypogastric plexus and with the ovarian plexus. The uterine nerves terminate in the myometrium and endometrium, and usually accompany the vessels. Nerves to the cervix form a plexus that contains small paracervical ganglia. Sometimes one ganglion is larger and is termed the uterine cervical ganglion. Branches may pass directly to the cervix uteri or may be distributed along the vaginal arteries.

Efferent preganglionic sympathetic fibres are derived from neurones in the last thoracic and first lumbar spinal segments; the sites where they synapse on their postganglionic neurones are unknown. Preganglionic parasympathetic fibres arise from neurones in the second to fourth sacral spinal segments and relay in the paracervical ganglia. Sympathetic activity may produce uterine contraction and vasoconstriction and parasympathetic activity may produce uterine inhibition and vasodilatation, but these activities are complicated by hormonal control of uterine functions.

Microstructure

Body of the uterus

The uterus is composed of three main layers. From its lumen outwards these are the endometrium (mucosa), myometrium (smooth muscle layer) and serosa (or adventitia) (Fig. 77.22).

Fig. 77.22 The uterus, uterine tubes and ovaries.

(From Sobotta 2006.)

Endometrium

The endometrium is formed by a layer of connective tissue, the endometrial stroma, which supports a single-layered columnar epithelium. Before puberty, the epithelium is ciliated and cuboidal. It contains glands which are composed largely of columnar cells secreting glycoproteins and glycogen. After puberty, the structure of the endometrium varies with the stage of the menstrual cycle (see below). The glands are tubular, run perpendicular to the luminal surface and penetrate up to the myometrial layer. The stroma consists of a highly cellular connective tissue between the endometrial glands, and contains blood and lymphatic vessels.

Myometrium

The myometrium is composed of smooth muscle and loose connective tissue and contains blood vessels, lymphatic vessels and nerves. It is dense and thick at the uterine midlevel and fundus but thin at the tubal orifices. The body of the uterus has four muscular layers. The submucosal (innermost) layer is composed of longitudinal and some oblique smooth muscle fibres. Where the lumen of the uterine tube passes through the uterine wall, this layer forms a circular muscle coat. The vascular layer is external to the submucosal layer and is rich in blood vessels as well as longitudinal muscle, it is succeeded by a layer of predominantly circular muscle, the supravascular layer. The outer, thin, longitudinal muscle layer, the subserosal layer, lies adjacent to the serosa.

The muscular fibres of the outer two layers converge at the lateral angles of the uterus, and continue into the uterine tubes. Some fibres enter the broad ligaments as the round and ovarian ligaments; others turn back into the uterosacral ligaments. At the junction between the body and the cervix, the smooth muscle merges with dense irregular connective tissue containing both collagen and elastin, and forms the majority of the cervical wall. Bilateral longitudinal fibres extend in the lateral submucosal layer from the fundal angle to the cervix. Their muscle fibres differ structurally from those of typical myometrium, and they may provide fast conducting pathways which coordinate the contractile activities of the uterine wall.

Serosa

The serosa is composed of peritoneum (mesothelium overlying a thin connective tissue lamina propria), which covers the uterine body. Posteriorly it continues downwards to cover the supravaginal cervix.

Cervix uteri

The cervix (Figs 77.23, 77.24) consists of fibroelastic connective tissue and contains relatively little smooth muscle. The elastin component of the cervical stroma is essential to the stretching capacity of the cervix during childbirth. The cervical canal is lined by a deeply folded mucosa with a surface epithelium of columnar mucous cells. There are branched tubular glands present amongst the mucosa, which are lined by a similar secretory epithelium. The glands extend obliquely upwards and outwards from the canal. They secrete clear, alkaline mucus, which is relatively viscous except at the midpoint of the menstrual cycle, when it becomes more copious and less viscous to encourage the passage of sperm. At the vaginal end of the cervix, the aperture of a gland may block and it then fills with mucus to form a Nabothian follicle (or cyst). None of the mucosa is shed during menstruation and so, unlike the body of the uterus, it is not divided into functional and basal layers and lacks spiral arteries. The surface of the intravaginal part of the cervix (ectocervix) is covered by non-keratinizing stratified squamous epithelium, which contains glycogen.

Fig. 77.23 Transformation zone of the uterine cervix. The single layered columnar epithelium lining the endocervical canal (EC) and its endocervical glands (EG) changes abruptly (arrow) to the stratified squamous non-keratinizing epithelium of the external os and ectocervix (below arrow).

Fig. 77.24 Endocervical glands are deep infoldings of the lining of the endocervical canal (EC). The epithelium (E) is simple columnar and mucus-secreting. The underlying lamina propria (LP) is richly supplied with blood vessels (BV) and lymphatics (L).

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

The squamocolumnar junction, where the columnar secretory epithelium of the endocervical canal meets the stratified squamous covering of the ectocervix, is located at the external os before puberty. As oestrogen levels rise during puberty, the cervical os opens, exposing the endocervical columnar epithelium onto the ectocervix. This area of columnar cells on the ectocervix forms an area that is red and raw in appearance called an ectropion (cervical erosion). It is then exposed to the acidic environment of the vagina and through a process of squamous metaplasia transforms into stratified squamous epithelium. This area is thus known as the ‘transformation zone’. Other hyperoestrogenic states such as pregnancy and the use of oral contraceptive pills can also result in an ectropion. This area is the most usual site of cervical intraepithelial neoplasia (CIN) that may progress to malignancy. In postmenopausal women, the squamo-columnar junction recedes into the endocervical canal (Fig. 77.23).

Magnetic resonance imaging of the uterus

On T2-weighted magnetic resonance imaging (MRI), the uterus (Fig. 77.25A,B) displays a zonal anatomy, with three distinct zones: the endometrium; junctional zone; and myometrium. The endometrium and uterine cavity appear as a high-signal stripe; the thickness varies with the stage of the menstrual cycle. In the early proliferative phase it measures up to 5 mm, and widens to up to 1 cm in the mid-secretory phase. A band of low signal, the junctional zone, borders the endometrium. It represents the inner myometrium, which blends with the low-signal band of fibrous cervical stroma at the level of the internal os. The junctional zone appears low signal because the cells of the myometrium have low water content when compared to those of the outer myometrium. The junctional zone is of constant thickness and signal throughout the menstrual cycle, and usually measures 5 mm. The outer myometrium is of medium signal intensity in the proliferative phase, and of high signal intensity in the mid-secretory phase as a result of the increased vascularity and prominence of the arcuate vessels.

Fig. 77.25 T2-weighted MRI scans of the uterus and ovaries. A, Coronal T2-weighted MRI through a female pelvis showing the uterus and both ovaries with the high signal central stroma and lower signal outer stroma. B, Sagittal T2-weighted MRI through a female pelvis showing the zonal anatomy of the uterus.

In prepubertal females, the uterus is smaller (only 4 cm in length) and on T2-weighted images the endometrium is minimal or absent, and the junctional zone is indistinct. In postmenopausal women, the corpus decreases in size and the zonal anatomy is indistinct.

On T2-weighted MRI the cervix has an inner low-signal stroma continuous with the junctional zone of the uterus. Often this is surrounded by an outer zone of intermediate signal intensity, which is continuous with the outer myometrium. The appearances do not change with the menstrual cycle or oral contraceptive pill use. The central stripe is very high signal and is a consequence of the secretions produced by the endocervical glands.

Vascular supply and lymphatic drainage

Innervation

The uterine tube is innervated by autonomic fibres that are distributed mainly with the ovarian and uterine arteries. Most of the tube has a dual sympathetic and parasympathetic supply. Preganglionic parasympathetic fibres are derived from the vagus for the lateral half of the tube, and pelvic splanchnic nerves for the medial half. Sympathetic supply is derived from neurones in the tenth thoracic to the second lumbar spinal segments. Visceral afferent fibres travel with the sympathetic nerves, and enter the cord through corresponding dorsal roots: they may also travel with parasympathetic fibres. The ampullary submucosa contains modified Pacinian corpuscles.

Microstructure

The walls of the uterine tubes show typical visceral mucosal, muscular and serosal layers (Fig. 77.28). The mucosa is thrown into longitudinal folds, which are most pronounced distally at the infundibulum and decrease to shallow bulges in the intrauterine (intramural) portion. The mucosa is lined by a single-layered, tall, columnar epithelium, which contains mainly ciliated cells and secretory (peg) cells (so-called because they project into the lumen further than their ciliated neighbours), and occasional intraepithelial lymphocytes. In the tube, ciliated cells predominate distally and secretory cells proximally. Their activities vary with the stage in the menstrual cycle and with age. Secretory cells are most active around the time of ovulation. Their secretions include nutrients for the gametes and aid capacitation of the spermatozoa. Ciliated cells increase in height and develop more cilia in the oestrogenic first half of the menstrual cycle. Their cilia waft the oocyte from the open-ended infundibulum towards the uterus in fluids secreted by the peg cells. The epithelium regresses in height towards the end of the cycle and postmenopausally, when ciliated cells are reduced in number.

Fig. 77.28 Uterine tube (ampulla) with the mucosal lining thrown into extensive folds that fill the lumen. The superficial epithelium includes both secretory and ciliated cells, covering a lamina propria (LP). Smooth muscle (SM) occupies the wall of the tube.

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

The lamina propria provides vascular connective tissue support and abundant lymphatic drainage vessels. The smooth muscle of the muscularis is arranged as an inner circular, or spiral, layer and an outer, thinner, longitudinal layer. Together, their contractile activity produces peristaltic movements of the tube, which assist propulsion of the gametes and the fertilized ovum. The uterine tubes are covered externally by a highly vascular serosa.

Peritoneal and ligamentous supports of the ovary

The peritoneal and ligamentous supports of the ovary consist of the infundibulopelvic, ovarian, and mesovarian ligaments.

Vascular supply and lymphatic drainage

Innervation

The ovarian innervation is derived from autonomic plexuses. The upper part of the ovarian plexus is formed from branches of the renal and aortic plexuses, and the lower part is reinforced from the superior and inferior hypogastric plexuses. These plexuses consist of postganglionic sympathetic, parasympathetic and visceral afferent fibres. The efferent sympathetic fibres are derived from the 10th and 11th thoracic spinal segments and are probably vasoconstrictor, whereas the parasympathetic fibres, from the inferior hypogastric plexuses, are probably vasodilator.

Microstructure

In young females the surface of the ovary is covered by a single layer of cuboidal epithelium, which contains some flatter cells. It appears dull white, in contrast to the shiny smooth peritoneal mesothelial covering of the mesovarium, with which it is continuous. A white line around the anterior mesovarian border usually marks the transition between peritoneum and ovarian epithelium. The surface epithelium is also termed the germinal epithelium, but this is a misnomer, because it is not the source of germ cells. Immediately beneath the epithelium there is a tough collagenous coat, the tunica albuginea. The ovarian tissue it surrounds is divisible into a cortex, which contains the ovarian follicles, and a medulla, which receives the ovarian vessels and nerves at the hilum.

Ovarian cortex

Before puberty, the cortex forms 35%, the medulla 20%, and interstitial cells up to 45%, of the volume of the ovary. After puberty the cortex forms the major part of the ovary, and encloses the medulla except at the hilum. It contains the ovarian follicles at various stages of development, and corpora lutea and their degenerative remnants, depending on age or stage of the menstrual cycle. The follicles and structures derived from them are embedded in a dense stroma composed of a meshwork of thin collagen fibres and fusiform fibroblast-like cells arranged in characteristic whorls. Stromal cells differ from fibroblasts in general connective tissue in that they contain lipid droplets, which accumulate in pregnancy. Stromal cells give rise to the thecal layers of maturing ovarian follicles. The theca interna becomes steroid-secreting in the corpus luteum.

Ovarian follicles

Primordial follicles

The development of ovarian follicles can be divided into different stages (Fig. 77.31). At birth, the ovarian cortex contains a superficial zone of primordial follicles. These consist of primary oocytes 25 μm in diameter, each surrounded by a single layer of flat follicular cells. The oocyte nuclei are slightly eccentric and have a characteristically prominent nucleolus. They contain the diploid number of chromosomes (duplicated as sister chromatids), arrested at the diplotene stage of meiotic prophase since before birth (Fig. 77.32). Many follicles degenerate either during prepubertal (including prenatal) life, or through atresia at some stage after beginning the process of cyclical maturation during the child-bearing period. Their remnants are visible as atretic follicles, the remains of which accumulate throughout the period of reproductive life. After puberty, cohorts of up to 20 primordial follicles become activated in each menstrual cycle (fewer are activated with advancing age). Their development takes a number of cycles. Of the follicles activated in each cohort, usually only one follicle from one or other ovary becomes dominant, reaches maturity and releases its oocyte at ovulation.

Fig. 77.31 The microstructure of the ovary and follicles at various stages in their cyclical development and the formation of corpora lutea and albicantes. Note that in the human ovary, developing follicles are rarely seen.

Fig. 77.32 High power ovarian cortex with primordial (p) and early primary (P) follicles within the stroma (S); stimulated primary follicles have cuboidal cells forming their wall. A large oocyte nucleus is visible in the plane of section of most of the follicles (arrow).

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

Primary follicles

Primary follicles develop from primordial follicles. The first sign is a change in the follicle cells from flattened to cuboidal. This is followed by their proliferation to give rise to a multilayered follicle consisting of granulosa cells surrounded by a thick basal lamina (Fig. 77.33). Stromal cells immediately surrounding the follicle begin to differentiate into spindle-shaped cells, which constitute the theca folliculi which will become the theca interna. They are later surrounded by a more fibrous layer called the theca externa. At the same time the oocyte increases in size and secretes a thick layer of extracellular proteoglycan-rich material, the zona pellucida, between its plasma membrane and the surrounding granulosa cells of the early follicle. This is important for the process of fertilization. The granulosa cells in contact with the zona pellucida send cytoplasmic processes radially inwards and these contact oocyte microvilli at gap junctions, indicating communication between them (see Motta et al 2003). The follicular cells, in particular the granulosa cells, which are in functional contact with each other through gap junctions, continue to proliferate and so the thickness of the late primary follicle wall increases.

Fig. 77.33 High magnification micrograph of a primary follicle in a human ovarian cortex. The pale oocyte, with its eccentric nucleus (N) is separated from the follicle (F) by the zona pellucida (arrow). Cells of the follicle wall are in the early stages of proliferation to form a multilayered, late primary follicle.

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

Secondary (antral) follicles

Secondary (antral) follicles develop from primary follicles. The number of granulosa cells continues to increase. Cavities begin to form between them filled with a clear fluid (liquor folliculi) containing hyaluronate, growth factors, and steroid hormones secreted by the granulosa cells. The follicle is now about 200 μm in diameter and usually lies deep in the cortex. These cavities coalesce to form one large fluid-filled space, the antrum. This is surrounded by a thin, uniform layer of granulosa cells, except at one pole of the follicle where a thickened granulosa layer envelops the eccentrically placed oocyte, to form the cumulus oophorus. The oocyte has now reached its maximum size of about 80 μm and the inner and outer thecae are clearly differentiated (Fig. 77.34). As follicles mature, the theca interna becomes more prominent and its cells more rounded and typical of steroid-secreting endocrine cells. These cells produce androstenedione from which the granulosa cells synthesize oestrogens (primarily oestradiol). Follicular development is stimulated by follicle-stimulating hormone (FSH).

Fig. 77.34 Antral (secondary) follicle, showing the layers of the developing follicle wall. Granulosa cells (GC) enclose the antrum (A) filled with liquor folliculi and surround the oocyte (not seen in the plane of section) within an eccentric cellular mass (right). The outer theca interna (TI) is a highly vascular layer which develops steriod secretory activity and is enclosed by the outermost theca externa (TE).

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

Tertiary (Graafian) follicle

Although a number of follicles may progress to the secondary stage by about the first week of a menstrual cycle, usually only one tertiary follicle develops. The remainder become atretic. The surviving follicle increases considerably in size as the antrum takes up fluid from the surrounding tissues and expands to a diameter of 2 cm. The term Graafian follicle is often used to describe this mature follicular stage (Fig. 77.34). The oocyte and a surrounding ring of tightly adherent cells, the corona radiata, breaks away from the follicle wall and floats freely in the follicular fluid. The primary oocyte, which has remained in the first meiotic prophase since fetal life, completes its first meiotic division to produce the almost equally large secondary oocyte and a small first polar body with very little cytoplasm. The secondary haploid oocyte immediately begins its second meiotic division, but when it reaches metaphase, the process is arrested until fertilization has occurred. The follicle moves to the superficial cortex, causing the surface of the ovary to bulge. The tissues at the point of contact (the stigma) with the tough tunica albuginea and ovarian surface epithelium are eroded until the follicle ruptures and its contents are released into the peritoneal cavity for capture by the fimbria of the uterine tube. The oocyte at ovulation is still surrounded by its zona pellucida and corona radiata of granulosa cells. If fertilization does not occur, it begins to degenerate after 24 to 48 hours.

Corpus luteum

After ovulation, the remainder of the follicle becomes the corpus luteum (Fig. 77.35). The walls of the empty follicle collapse and fold. The granulosa cells increase in size and synthesize a cytoplasmic carotenoid pigment (lutein) giving them a yellowish colour (hence corpus luteum). These large (30–50 μm) granulosa lutein cells form most of the corpus luteum. The basal lamina surrounding the follicle breaks down, and numerous smaller theca lutein cells infiltrate the folds of the cellular mass, accompanied by capillaries and connective tissue. Extravasated blood from thecal capillaries accumulates in the centre as a small clot, but this rapidly resolves and is replaced by connective tissue. All lutein cells have a cytoplasm filled with abundant smooth endoplasmic reticulum, characteristic of steroid synthesizing endocrine cells. Granulosa lutein cells secrete progesterone and oestradiol (from aromatization of androstenedione, which is synthesized by theca lutein cells). The two cell types also respond differently to circulating gonadotropins. Theca lutein cells express receptors for human chorionic gonadotrophin (hCG). If the oocyte is not fertilized, the corpus luteum (of menstruation) functions for 12 to 14 days after ovulation, then atrophies. The lutein cells undergo fatty degeneration, autolysis, removal by macrophages and gradual replacement with fibrous tissue. Eventually, after 2 months, a small, whitish scar-like corpus albicans is all that remains.

Fig. 77.35 Low power view of a section of a human ovary, containing a corpus luteum (C).

(By courtesy of Mr Peter Helliwell and Dr Joseph Mathew, Department of Histopathology, Royal Cornwall Hospitals Trust, UK.)

If fertilization does occur, implantation of the blastocyst into the uterine endometrium usually begins seven days later and the embryonic trophoblast then starts to produce hCG. The chorionic gonadotrophin stimulates the corpus luteum of menstruation to grow, and it becomes a corpus luteum of pregnancy. It normally increases in size from 10 mm in diameter to 25 mm at 8 weeks of gestation and can be seen clearly on ultrasound. It secretes progesterone, oestrogen and relaxin, and functions throughout pregnancy, although it gradually regresses as its endocrine functions are largely replaced by the placenta after 8 weeks gestation. Its diameter is reduced by the end of pregnancy to 1 cm. In the next few months it degenerates, like the corpus luteum of menstruation, to form a corpus albicans.

Growth of the uterus in pregnancy

Anatomical surface landmarks can be used to estimate uterine size and therefore gestational age. The uterus is usually palpable just above the pubic symphysis by the 12th week; if is retroverted it may not be palpable in the abdomen until a little later. By the 20th week of pregnancy the uterine fundus is at the level of the umbilicus, and by 36 weeks the fundus has reached the xiphisternum. In practice the gestational age is now calculated by ultrasound measurement of the fetal crown–rump length in the first trimester (Fig. 77.39). For women presenting after the first trimester, dating is less accurate and is based on measurement of the head circumference. Subsequent assessment of fetal size up to 24 weeks relies on abdominal palpation and correlating gestational age with anatomical landmarks. From 24 weeks of gestation serial measurement of the distance between the pubic symphysis and the uterine fundus is used. The symphysis–fundal height (SFH) measurement acts primarily as a screening method, and if there is a concern that the SFH is either above or below the normal range a more accurate assessment of fetal size and amniotic fluid volume is made using ultrasound. Dating of pregnancy based on fetal biometry rather than menstrual history has significantly reduced the number of pregnancies requiring induction of labour for post-term.

Fig. 77.39 Transabdominal ultrasound at 12 weeks showing measurement of the crown rump length to calculate the gestational age.

Doppler can be used to assess the placental and fetal circulations. Doppler assessment of the uterine arteries can play an important role in screening for impaired placentation and its complications of pre-eclampsia, intrauterine growth restriction and perinatal death, and assessment of the fetal circulation (e.g. umbilical artery, middle cerebral artery) can aid clinical management, such as timing of delivery in a growth restricted baby (Fig. 77.40A,B).

Fig. 77.40 Doppler examination of the maternal and fetal circulation in pregnancy. A, Pulsed Doppler showing a normal uterine artery waveform at 24 weeks. B, Pulsed Doppler showing normal waveforms in the middle cerebral artery at 32 weeks.

Cervix and pregnancy

The uterine cervix is required to serve two functions in relation to pregnancy and parturition. During pregnancy it is a relatively rigid fibromuscular structure which retains the developing fetus within the uterus. During active labour the cervix dilates to allow the fetus to descend through the birth canal. Considerable softening and shortening of the cervix occurs in the weeks before the onset of labour; a corresponding increase in uterine activity is usually apparent during this pre-labour period. The rigidity of the cervix appears to be related to the orientation of its collagen fibres within a regular connective tissue matrix. The exact processes that allow softening, effacement and dilatation of the cervix are unclear, but are believed to include remodeling of the connective tissue matrix, probably mediated by an increase in the activity of enzymes such as matrix metalloproteinase 1, a reduction in collagen concentration, a significant increase in the water content in the cervix, an infiltration of macrophages and neutrophils, and an increased level of apoptosis.

The cervix can be viewed during pregnancy by transvaginal ultrasound examination. The cervical length, dilatation of the internal os and bulging of the membranes into the canal can be assessed (Fig. 77.41A,B). Measurement of cervical length on ultrasound appears to be a strong predictor of preterm labour: the shorter the cervix, the greater the risk of premature delivery. In clinical practice cervical length has been used to screen women at high risk of preterm labour or to screen symptomatic women in threatened preterm labour in order to plan appropriate management.

Fig. 77.41 Transvaginal ultrasound at 36 weeks showing (A) measurement of cervical length and (B) posterior placenta praevia 18.5 mm from the internal os.

Relations of the uterus in pregnancy

With uterine expansion, the ovaries and uterine tubes are displaced upwards and laterally. The round ligaments become hypertrophied and their course from the cornual regions of the uterus down to the internal inguinal ring becomes more vertical. The broad ligament tends to open out to accommodate the massive increase in the sizes of the uterine and ovarian vessels. The uterine veins in particular can reach about 1 cm in diameter and they appear to act as a significant reservoir for blood during uterine contractions. Lymphatics and nerves expand their territories (the significance of this increased innervation is not clear, because paraplegic women are able to labour normally, albeit painlessly). Later in pregnancy the increase in intra-abdominal pressure produced by the gravid uterus may produce eversion of the umbilicus. On the skin over the abdomen, a combination of stretching and hormonal changes may produce stretch marks (striae gravidarum). In multiparous patients, separation (diverification) of right and left rectus abdominis may occur allowing the uterine fundus to fall forwards to some extent. In the supine position, the pregnant woman in late pregnancy is vulnerable to aorto-caval compression, as the gravid uterus presses on, and reduces blood flow in, the great vessels. Aorto-caval compression can cause symptoms of nausea and faintness; these symptoms are minimized if the woman lies on her left side thereby reducing compression of the inferior vena cava.

The jejunum, ileum and transverse colon tend to be displaced upwards by the enlarging uterus, whereas the caecum and appendix are displaced to the right, and the sigmoid colon posteriorly and to the left. Upward and lateral displacement of the appendix in later pregnancy can cause difficulties in the diagnosis of appendicitis. The ureters are pushed laterally by the enlarging uterus and in late pregnancy can be compressed at the level of the pelvic brim, resulting in hydronephrosis and loin pain. However, mild ureteric dilatation is normal in pregnancy, and is caused by progesterone-induced relaxation of smooth muscle in the ureteric walls. The axis of the uterus is shifted or dextrorotated by the presence of the sigmoid colon which may lead to inadvertent incision into large uterine vessels at the time of lower segment caesarean section unless the operator is aware of any such rotation.

The placenta after delivery

Separation of the placenta from the uterine wall takes place along the plane of the stratum spongiosum. It extends beyond the placental area, detaching the villous placenta, with associated fibrinoid matrix and small amounts of decidua basale, the chorio-amnion, together with a superficial layer of the fused decidua capsularis, and the decidua parietalis. When the placenta and membranes have been expelled, a thin layer of stratum spongiosum is left as a lining for the uterus: it soon degenerates and is cast off in the early part of the puerperium. A new epithelial lining for the uterus is regenerated from the remaining stratum basale. The expelled placenta is a flattened discoid mass with an approximately circular or oval outline (Fig. 77.45). It has an average volume of 500 ml (range 200–950 ml), a weight of 470 g (range 200–800 g), a diameter of 185 mm (range 150–200 mm), a thickness of 23 mm (range 10–40 mm), and a surface area of approximately 30,000 mm². It is thickest at its centre (the original embryonic pole), and rapidly thins towards its periphery where it continues as the chorion laeve.

Fig. 77.45 The fetal surface of a recently delivered placenta. The spiral umbilical vessels in the umbilical cord and their radiating branches shine through the transparent amnion. The maternal surface is exposed in the lower and right corner of the figure. Note the fringes of amnion and chorion, the majority of which have been cut away near the placental margin.

Macroscopically, the fetal or inner surface, covered by amnion, is smooth, shiny and transparent, so that the mottled appearance of the subjacent chorion, to which it is closely applied, can be seen. The umbilical cord is usually attached near the centre of the fetal surface, and branches of the umbilical vessels radiate out under the amnion from this point; the veins are deeper and larger than the arteries. The maternal surface of the placenta is finely granular and mapped into some 15–30 lobes by a series of fissures or grooves. The placental lobes, which are often somewhat loosely termed cotyledons, correspond in large measure to the major branches of the umbilical vessels. The grooves correspond to the bases of incomplete placental septa, which become increasingly prominent from the third month onwards. They extend from the maternal aspect of the intervillous space (the basal plate) towards, but do not quite reach, the chorionic plate. The septa are complex structures composed of components of the cytotrophoblastic shell and residual syncytium, together with maternally derived material including decidual cells, occasional blood vessels and gland remnants, collagenous and fibrinoid extracellular matrix and, in the later months of pregnancy, foci of degeneration.

In multiple pregnancies the number of placentas is determined by the zygosity. Dizygotic pregnancies will always have two placentas (dichorionic); monozygotic pregnancies usually have a single placenta (monochorionic) but 33% will have two placentas. The number of placentas in monozygotic pregnancies is determined by the timing of splitting of the embryonic mass. If the single embryonic mass splits into two within 3 days of fertilization, each fetus will have its own placenta and amniotic sac (dichorionic diamniotic); splitting after the 3rd day following fertilization results in a monochorionic diamniotic (two amniotic sacs) pregnancy and vascular communication within the two placental circulations (Fig. 77.46); splitting after the 9th day results in a single placenta and single amniotic sac (monochorionic monoamniotic); and splitting after the 12th day results in conjoined twins.

Fig. 77.46 Vascular cast from a monochorionic diamniotic twin pregnancy showing vascular communications between both placentas.

(By courtesy of Dr Ling Wee, University College London Hospital.)

Placental variations

The umbilical cord is usually attached near the centre of the placenta. It may insert at any point between its centre and margin, a condition known as a battledore placenta (Fig. 77.47). Occasionally the cord fails to reach the placenta itself and ends in the membranes as a velamentous insertion. When insertion of the cord is velamentous, the larger branches of the umbilical vessels traverse the membranes before they reach and ramify on the placenta (Fig. 77.48). They travel unprotected through the membranes to the placenta, which puts the fetus at risk because compression or tearing of the vessels can disrupt blood flow to and from the fetus. This can be particularly problematic when the vessels present themselves across the cervical os, a condition called vaso previa. A small accessory (succenturiate) placental lobe is occasionally present, connected to the main organ by membranes and blood vessels. It may be retained in utero after delivery of the main placental mass and cause postpartum haemorrhage. Other variations include placenta membranacea, in which villous stems and their branches persist over the whole chorion; and placenta circumvallate, where the placental margin is undercut by a deep groove (Fig. 77.49A,B).

Fig. 77.47 A battledore placenta showing marginal insertion of the umbilical cord into the placenta.

(By courtesy of Dr Michael Ashworth, Consultant Histopathologist, Great Ormond Street Hospital for Children, London.)

Fig. 77.48 Velamentous insertion of the umbilical cord showing the cord inserting into the chorioamniotic membranes rather than the placental disk.

(By courtesy of Dr Michael Ashworth, Consultant Histopathologist, Great Ormond Street Hospital for Children, London.)

Fig. 77.49 Placenta circumvallata. A, showing the fetal surface and a thick ring of membranes on the fetal surface of the placenta. B, A section through the placenta showing that the membranes insert central to the edge of the placental disk.

(By courtesy of Dr Michael Ashworth, Consultant Histopathologist, Great Ormond Street Hospital for Children, London.)