Chapter 2 – Anatomy and Physiology of the Uterus




Abstract




The uterus is the primary female reproductive organ. It is situated within the pelvis and measures approximately 8 cm in length, 4 cm in width and 5 cm in depth in the normal, non-pregnant state. Though relatively quiescent in pre-pubertal and post-menopausal years, the uterus possesses a variety of functions during a woman’s reproductive years. It responds to the production of female hormones, creating changes to allow for implantation of a fertilised egg, or menstruation when pregnancy does not occur. It is also able to rapidly expand with the development of a pregnancy and has a contractile function for labour and delivery during childbirth [1].





Chapter 2 Anatomy and Physiology of the Uterus


Christopher Guyer , Sree Rajesh and Mary E. Connor



2.1 Introduction


The uterus is the primary female reproductive organ. It is situated within the pelvis and measures approximately 8 cm in length, 4 cm in width and 5 cm in depth in the normal, non-pregnant state. Though relatively quiescent in pre-pubertal and post-menopausal years, the uterus possesses a variety of functions during a woman’s reproductive years. It responds to the production of female hormones, creating changes to allow for implantation of a fertilised egg, or menstruation when pregnancy does not occur. It is also able to rapidly expand with the development of a pregnancy and has a contractile function for labour and delivery during childbirth [1].


The embryological development of the female genital tract must be understood to appreciate its very specialised function and to identify and address congenital anomalies that occasionally occur. A detailed knowledge of the structure and function of all aspects of the genital tract is also important so that abnormalities can be recognised and managed.



2.2 Uterine Anatomy



2.2.1 Embryology


Congenital uterine anomalies usually arise during organogenesis, early in the development of the genital tract in the first trimester of pregnancy, though some may occur later in fetal life. The renal and genital systems are intimately linked, having shared origins, so there may be a renal tract anomaly alongside a disorder in the genital tract. Formation of the gonads is independent of the urogenital tract, though an absence of the urogenital ridge would result in an absence of the gonad on that side [2].


Gonadal development commences during the fifth week of embryonic life, starting with primitive germ cells migrating to the mesothelium of the posterior abdominal wall and adjacent mesenchyme on the medial border of the urogenital ridge. The gonads are indifferent at this stage and remain so until the twelfth week. Development of the genital tract depends upon the sex chromosomes and associated hormonal production: with two X chromosomes, or absence of male hormone production, the female genital tract develops; with XY chromosomes and appropriate protein hormone production, a male fetus develops.


Lateral to the developing gonads, renal development commences, initially with the pronephros, then the mesonephros, followed by the metanephros, which becomes the permanent kidney [3]. Drainage ducts – the Wolffian or mesonephric ducts – originate from the mesonephros and grow to the cloaca, fusing with the urogenital sinus. Ureteral buds arise at this point and grow to the metanephros, becoming the ureters.


During the seventh to eighth week, paired Müllerian or paramesonephric ducts develop, arising from the coelomic cavity on the lateral border of the urogenital ridge. The paired Wolffian and Müllerian ducts grow caudally, and initially in parallel. The presence of the Wolffian ducts is regarded as essential for the growth of the Müllerian ducts [4]. The Müllerian ducts subsequently grow medially and ventrally to the Wolffian ducts, then meet and fuse in the midline to become the uterine primordium. The ducts cephalic to the fused portion remain separate and form the fallopian tubes, with the opening into the coelomic cavity retained. A septum within the uterine cavity may be evident up to the twentieth week of development, but then usually regresses.


It is established that the Müllerian ducts form the fallopian tubes and uterus, including the cervix. Development of the vagina, though, has been an area of controversy for over 100 years. In 1957, Bulmer [5] summarised the three theory groups as follows:




  1. a. the vagina is entirely Müllerian in origin (classic theory)



  2. b. the vaginal epithelium, in part or whole, is derived from the lower ends of the Wolffian ducts



  3. c. the urogenital sinus (sino-vaginal bulbs) contributes to the vagina to produce either:




    1. i. the lower fifth of the vagina, with the upper vagina produced from the Müllerian tubes; or



    2. ii. the entire vaginal epithelium.



More recently, some authors have considered the issue resolved, confirming the vagina as deriving from the Müllerian ducts [6] (Figure 2.1a).





Figure 2.1 Vaginal development theories [4]. (a) Classic theory: the vagina forms from the Müllerian ducts and urogenital sinus. (b) Evolution of the Wolffian and Müllerian ducts according to Acién: diverging portions of the Müllerian ducts fuse with the distal segments of the Wolffian ducts, forming the sinus bulbs; the Müllerian tubercle remains as a cluster of cells between them; the cervix derives from the diverging Müllerian ducts, and the vagina from the distal segments of the Wolffian ducts with an internal lining from the Müllerian tubercle.


Reproduced with permission from [4].

However, other authors, such as Acién and colleagues, are dissatisfied with all of the above concepts, believing that they fail to provide an understanding of certain particularly complex congenital anomalies [2, 4]. They propose that the Müllerian ducts diverge as they grow beyond the uterine primordium and fuse caudally with the distal Wolffian ducts and urogenital sinus, which they regard as also of Wolffian origin [4]. Between these elements they describe the Müllerian tubercle, a cluster of mesenchymal cells, with the urogenital sinus at its base. Acién and co-authors argue that the cervix is formed from the divergent Müllerian ducts, with the start of the divergence becoming the internal cervical os and the most distal end the external cervical os. Their interpretation of human vaginal development, from work on rat embryos, is that none of it is derived from the Müllerian ducts. Instead, they believe that the vaginal walls are from cells of the Wolffian ducts, with the epithelial lining derived from the Müllerian tubercle (Figure 2.1b).


Knowledge of the embryology of the urogenital system should help us understand congenital anomalies [2, 8] (Table 2.1).




Table 2.1 Embryological disorders and associated congenital anomalies of the female genital tract






















Embryological disorder Genital tract malformation
1. Agenesis or hypoplasia of a whole urogenital ridge Ipsilateral absence of kidney, functioning ovary, fallopian tube, hemiuterus and hemivagina (undetectable); possible vertebral and/or auditory anomaly
2. Wolffian (mesonephric) anomalies with absence of urogenital sinus and of ureteral bud sprouting


  • Renal agenesis or hyoplasia and ectopic ureter with ipsilateral blind vagina



  • Uterine anomaly due to absence of Wolffian induction of Müllerian duct, such as double uterus with or without communication:



  • A. Large haematocolpos in the blind vagina



  • B. Gartner’s pseudocyst in the anterolateral wall of the vagina



  • C. Partial reabsorption of the intervaginal septum (buttonhole) on the anterolateral wall of the vagina



  • D. Complete unilateral vaginal or cervico-vaginal agenesis




  • 3. Isolated Müllerian (paramesonephric) anomalies



  • A. Müllerian duct



  • B. Müllerian tubercle



  • C. Müllerian duct and tubercle




  • A. Uterine and/or fallopian tube anomalies, sometimes segmentary: unicornuate, bicornuate, didelphys, septate uterus



  • B. Vaginal (or cervico-vaginal) agenesis or atresia and segmentary atresias (transverse vaginal septum)



  • C. Mayer–Rokitansky–Kuster–Hauser syndrome (uni- or bilateral)

4. Anomalies of the urogenital sinus Imperforate hymen with persistent urogenital membrane, cloacal anomalies and others

Data from [2].

The American Society for Reproductive Medicine (ASRM) [9] (Figure 2.2) and, more recently, the European Society for Gynaecological Endoscopy with the European Society of Human Reproduction and Embryology (ESGE–ESHRE) [10] (Figure 2.3) have classified congenital uterine malformations to help clinically assess women diagnosed with congenital anomalies and decide on therapeutic options [11].





Figure 2.2 ASRM classification of uterine abnormalities [9].





Figure 2.3 ESGE–ESHRE classification of uterine abnormalities [10].


The newer ESGE–ESHRE classification has been designed to improve objectivity surrounding the diagnosis of uterine anomalies and is based on anatomical changes. It includes abnormalities of the cervix and vagina. However, whether this provides a clinically superior assessment to the ASRM classification remains debated [2, 12].



2.2.2 Uterine Anatomy and Function


The uterus is composed of three distinct areas – the cervix, the uterine body and the fallopian tubes – each with their own specific structure and function (Figure 2.4).





Figure 2.4 Uterus, ovaries and fallopian tubes.



Cervix

The cervix is a fibromuscular structure approximately 2 cm in length. It is composed of two distinct areas: the endocervix, which comprises the upper portion of the cervix beneath the uterus and is lined by columnar glandular epithelium, and the lower ectocervix, which is joined to the vagina and is lined by stratified squamous epithelium.


The cervix functions as a passage through which menstrual blood passes out of the uterus, and spermatozoa pass into the reproductive system for fertilisation. Mucus produced by the endocervix changes under the influence of the female hormones. For much of the time it remains thick and viscous, forming a barrier to the uterine cavity, but at the time of ovulation it becomes less viscous, aiding the transit of spermatozoa into the uterine cavity.



Uterine Body


Endometrium

The primary function of the endometrium is to receive the conceptus after fertilisation and to enable the growth of the embryo and fetus. The endometrium is primed before ovulation in the proliferative and early secretory phases; the rich uterine blood supply from the myometrium into the endometrium is essential.


The endometrium is a glandular mucous membrane and forms the inner epithelial layer of the uterine cavity. It consists of a single superficial layer of columnar epithelium containing ciliated and secretory cells, which overlies a stromal layer, of varying thickness during the menstrual cycle, containing numerous tubular endometrial glands that extend deep into the stroma, but usually no further. The blood supply to this layer is rich and consists of small basal arteries that extend upwards from the basal layer of the endometrium into the stromal layer, representing an extensive network of tightly coiled arterioles.


From the menarche to the menopause, the endometrium undergoes cyclic changes, generally monthly, in response to the ovarian hormones. The stroma increases in thickness following menstruation during the follicular or proliferative phase of the cycle, in response to oestrogen stimulation. The coiled arterioles become longer and somewhat straighter, but remain in the lower two-thirds of the endometrium. Soon after ovulation, as progesterone is released from the corpus luteum in the ovary, the endometrium progresses into the secretory or luteal phase. Further thickening of the stroma occurs due to oedema and accumulation of secretions in the uterine glands. The glands continue to grow, becoming more tortuous and with widening lumens. The coiled arterioles become more prominent as they elongate.


The menstrual phase occurs when there is no fertilisation; the corpus luteum collapses and the progesterone levels fall. In response, the coiled arterioles constrict, causing blanching of the superficial endometrium; the glands stop producing secretions and there is a loss of interstitial fluid, so the endometrium shrinks. The arterioles in the surface endometrium close off, but the vessels in the basal layer continue. Menstruation is a consequence of the constricted arteries opening briefly and the superficial vessels (arteries and veins) bursting, releasing blood into the stroma that then passes into the uterine cavity. The menstrual discharge consists of altered arterial and venous blood, stromal and epithelial cells at various stages of disintegration and secretions from the genital tract. In normal menstruation blood clots do not form, owing to the action of proteolytic enzymes within the menstrual fluid [13].


In non-ovulatory cycles the secretory phase is absent and the endometrium proliferates until menstruation occurs spontaneously, and usually in a more haphazard fashion.


Towards the end of menstruation, the endometrium is at its thinnest. The basal layer is not shed during menstruation but remains intact, and is the source of regenerative endometrium. The superficial epithelial layer is rapidly regenerated and the stroma is restored as a new follicular phase commences.


Surgical therapies for the management of heavy menstrual bleeding, such as endometrial ablation and resection, target the basal layer of the endometrium. Once destroyed, the endometrium does not regrow, so menstrual shedding is reduced or stopped.



Myometrium

While it has long been established that the myometrial smooth muscle has a contractile function in childbirth, it is now apparent that there is continuous peristaltic activity within the non-pregnant uterus [14], although it excludes the main part of the myometrium [15]. It appears from magnetic resonance imaging (MRI), video-vaginosonography and immunohistochemical studies that, in addition to serosal epithelium, the human uterus consists of three, rather than two, distinct layers during the reproductive years [15, 16], and this supports the work published over a century ago by Werth and Grusdew [15] (Figure 2.5).





Figure 2.5 Myometrial layers: the thin, innermost circular subendometrial layer may facilitate the changing vectors of ‘endometrial waves’ that might be important in common reproductive disorders; the outer layer is probably more important for intense uterine activity, including miscarriage and labour [16].


The uterine cavity lining of endometrium and the thick outer myometrial layers are easily recognised, but less obvious is an inner layer – the subendometrial myometrium or ‘junctional zone’ [16] – which is said to be structurally and functionally different from the outer myometrial layer [15]. The endometrial and junctional zone layers may derive from the Müllerian ducts and are rich in oestrogen and progesterone receptors that are regulated during the menstrual cycle [17]. By contrast, the thick outer myometrium is thought to be derived from the surrounding mesenchyme and has steroid receptor activity that is constant throughout the cycle. Junctional zone development appears to be in response to the gonadal hormones, as it is not apparent in pre-pubertal girls; it disappears with the menopause and with induced oestrogen suppression with gonatotrophin-releasing hormone (GnRH) agonists, and reappears in women taking hormone replacement therapy [15]. The junctional zone is reported to thicken in women who are subfertile or have dysmenorrhoea or menorrhagia [15].


In the non-pregnant human uterus, the junctional zone seems to be the source of contractile activity, and these contractions or ‘endometrial waves’ can be observed throughout the menstrual cycle [14, 16]. There is evidence that the endometrial waves change in direction, frequency, duration and amplitude during the menstrual cycle [16]. The contractile activity may be important for sperm transport and encourages fundal implantation of the conceptus following fertilisation [16, 18].


Abnormalities of myometrial activity are considered to underlie the development of conditions such as endometriosis and adenomyosis [15]. MRI has also provided some insight into the impact that pathological changes, such as fibroids, may have on myometrial function [15, 19]. Treatments such as uterine artery embolisation [20] or myomectomy [21] may improve peristaltic function and hence improve fertility. As a consequence, there is much interest in the development of cine-MRI to measure uterine peristalsis [19, 22].


Despite the frequency with which uterine fibroids are encountered (33% prevalence on clinical examination, 50% on ultrasound scan and 77% on histopathological examination of hysterectomy specimens [23]), their aetiology remains unknown. Risk factors include ethnic origin, with black women disproportionately affected, nulliparity, age over 30 years and obesity. Oestrogen can cause an increase in growth of fibroids and there are more oestrogen receptors in fibroid tissue than in normal myometrium; progesterone receptors are also more numerous in fibroids than in normal myometrium [23]. Fibroids, though asymptomatic in many women, are recognised as a cause of abnormal uterine bleeding [24]. There are likely to be many mechanisms for their action [25], with submucosal fibroids that distort the uterine cavity more obviously implicated in both abnormal uterine bleeding and early pregnancy loss.

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Sep 17, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on Chapter 2 – Anatomy and Physiology of the Uterus
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