The adolescent female: Breast and reproductive embryology and anatomy

Abstract

Congenital breast and genital tract anomalies are seen frequently in the care of children and adolescents. Breast and internal gynecologic anomalies more often present in adolescence than in early childhood. Management is best delivered through a multidisciplinary team approach. Carefully timed surgical intervention is of importance to optimize psychological, aesthetic and functional outcomes. An understanding of the female breast and genital tract embryology and anatomy is important for a meticulous clinical examination and appropriate surgical treatment. This article will review the normal embryology and anatomy of theadolescent female breast and genital tract. Clin. Anat. 26:22–28, 2013. © 2012 Wiley Periodicals, Inc.

INTRODUCTION

Throughout life, the breast and genital tract undergo a series of changes, with the majority of growth occurring during puberty. In teenagers, normal breast and genital tract development plays a significant role in healthy psychological growth. A variety of breast and gynecological abnormalities in adolescents may require surgical interventions, which can have a profound influence on self-confidence and satisfaction with body image. An understanding of the female adolescent breast and reproductive system development and anatomy is the foundation for accurate evaluation, diagnosis, and treatment of congenital, developmental, and pathological anomalies.

BREAST

Embryology of the Breast

The breast or mammary gland is a modified type of apocrine sweat gland, which begins to develop at approximately the fifth week of fetal development. An array of local and systemic growth factors and hormones regulate this sequence of highly ordered events. The breast originates from paired linear ectodermal ridges or mammary ridges (Moore and Persaud,1998; Hunt et al.,2010), which are thickened strips of ectoderm extending bilaterally on the ventral surface of the embryo from the axillary to the inguinal regions. These epithelial cords initially appear as 15–20 buds. During the seventh week in utero, these buds undergo apoptosis in human embryos, with a single pair of solid buds persisting at the fourth or fifth intercostal space: the primary mammary buds. Incomplete involution of the linear ectodermal ridge leads to the development of ectopic breast tissue (polymastia) and/or supernumerary nipples (polythelia) along the mammary ridge, which may be found in 1–6% of individuals (Sabel,2009). The breasts subsequently begin to develop as these primary buds of ectoderm penetrate downward into the underlying mesoderm. By the 12^th week of gestation, the primary mammary buds burgeon into secondary buds, which will eventually form the mammary lobules. In the fifth month in utero, the mammary ridge penetrates the underlying mesoderm, sending 15–20 branching ingrowths radially into the developing breast (Moore and Persaud,1998). Small lumina develop within the mammary buds, forming the lactiferous ducts and their branches. The lactiferous ducts converge to open into a shallow mammary pit, which transforms into a nipple during infancy. During the second trimester, the breast development continues with the formation of sweat glands, sebaceous glands, and apocrine glands, which will eventually form the Montgomery glands. The areola also develops at approximately 5 months of gestational age. At birth, males and females have identical breasts, formed by the major lactiferous ducts. Shortly after birth, the nipple begins to protrude from the areola (Pandya and Moore,2011), encompassing 10–15 terminal duct outlets.

Normal Breast Development

At birth, the breast is composed of 15–20 radially arranged mammary lobes draining into ampullae via the main lactiferous ducts, which contain colostrum. The formation of colostrum is stimulated by placental hormones and is present in newborns between postpartum days 4 and 7. Therefore, a milky nipple discharge is normal at this age and in either sex. During the first 2 years of life, further branching and terminal lobule development continues. Between 2 years and until thelarche, breast development is suspended.

The biology of breast and pubic hair development is governed by the hypothalamic pituitary gonadal axis and hypothalamic pituitary adrenal axis, respectively (Christensen et al.,2010). Puberty in girls in North America normally begins between 8 and 12 years of age when the hypothalamus releases increasing levels of gonadotropin-releasing hormone (GnRH). (There are geographic, racial, and ethnic variations in the normal age range for puberty). Under the influence of GnRH the pituitary gland secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in the maturation of the ovarian follicles and the production of estrogens and progestins. The mammary ductal epithelium and surrounding stroma proliferate under the influence of ovarian estrogen, leading to proliferation of collecting ducts, terminal duct lobular units, and breast buds (Sabel,2009). Simultaneously, vascular and connective tissue elements proliferate, and the overall breast volume increases. In 1976, Tanner (Tanner and Whitehouse,1976) described the most commonly used system for breast and pubic hair development staging in adolescents (Table 1).

Table 1. Tanner's Breast Developmental Stages

Stage I (Preadolescent):

Papilla elevation above the level of the chest wall.

Stage II (Breast budding):

Breast and papilla elevation, along with increased areola diameter.

Stage III:

Ongoing enlargement of the breasts and areolae.

Stage IV:

Elevation of the areola and papilla above the breast mound.

Stage V (Mature breast):

Elevation of the papilla with regression of the areola.

Anatomy of the Breast and Nipple–Areolar Complex

The female breast lies on the anterior chest wall, extending from the second intercostal space superiorly to the inframammary fold at the sixth or seventh intercostal space inferiorly. On its transverse axis, the breast spans medially from the lateral border of the sternum to the midaxillary line laterally (Hunt et al.,2010). Approximately two-thirds of the deep surface of the breast overly the pectoralis major muscle fascia, with the lower lateral thirds covering the serratus anterior muscle and also the upper portion of the external oblique and rectus abdominis muscles. The axillary tail of Spence extends laterally toward the axilla. The shape, contour, volume, and density of the breasts vary significantly among individuals. The breast can be divided into quadrants: the upper inner, upper outer, lower inner, and lower outer quadrants. The upper outer quadrant tends to contain more fibroglandular tissue than the remainder of the breast. It is also the most frequent location of tumors of the breast.

The breast is composed of skin, adipose tissue, and fibroglandular breast tissue. The breast skin is usually thin and contains hair follicles, sebaceous glands as well as eccrine sweat glands. The subcutaneous tissue lies immediately under the skin. Beneath this layer lies the superficial fascia, within which is located the fibroglandular breast tissue. The deep fascia lies anterior to the pectoralis major muscle fascia. These two structures are separated by the retromammary bursa or space, mostly consisting of loose areolar tissue, which allows breast mobility on the chest wall. Fibrous bands of connective tissue (Cooper's suspensory ligaments) travel through the breast, where they connect the superficial and deep fascia and insert perpendicularly into the dermis. The fibroglandular tissue, or breast parenchyma, is composed of 15–20 lobes, each divided into 20–40 lobules, in turn consisting of 10–100 alveoli. Each breast lobe contains minor interlobular ducts, which drain into major lactiferous ducts, which dilate into subareolar lactiferous ampullae. Ten major collecting milk ducts then open at the nipple (Fig. 1).

Figure 1. Anatomy of the female breast.

In a breast without ptosis, the nipple is located at the level of the fourth intercostal space. The nipple–areolar complex is dense in basal melanin deposition and becomes darker during puberty. Multiple sensory nerve endings are located in the nipple, including Ruffini corpuscles (mechanoreceptors) and Krause end bulbs (thermoreceptors). The areola contains sebaceous glands and apocrine sweat glands. Scattered at the periphery of the areola are the Morgagni tubercles, nodular elevations formed by the openings of the Montgomery glands (Sabel,2009; Pandya and Moore,2011). Radially arranged smooth muscle fibers extend toward the dermis of the nipple and are responsible for nipple erection with stimulation.

Blood Supply

The breast receives its main blood supply from three sources: (i) medially located internal mammary perforators, which account for 60% of the blood supply to the breast; (ii) branches of the lateral thoracic artery, which supplies 30% of the vascular supply to the breast; and (iii) minor contributions from the thoracoacromial, intercostals, subscapular, and thoracodorsal arteries (Sabel,2009; Hunt et al.,2010). The breast skin is supplied by a rich subdermal plexus, which is in communication with the deeper vessels supplying the breast parenchyma. The venous drainage of the breast courses toward the axilla, following the course of the arteries. Part of the venous drainage also travels to the circulus venosus, an anastomotic circle in the subcutaneous tissue beneath the nipple-areolar complex.

Sensory Innervation

Lateral and anterior cutaneous branches of the third through sixth intercostal nerves provide the sensory innervation of the breast and the anterolateral chest wall. These branches course between slips of the serratus anterior muscle. Cutaneous branches arising from the anterior branches of the supraclavicular nerve supply the skin of the upper portion of the breast. Supplying sensation over the medial aspect of the upper arm, the intercostobrachial nerve is the lateral cutaneous branch of the second intercostal nerve. It is encountered during axillary dissection.

Lymphatic Drainage

Twenty to thirty axillary lymph nodes constitute more than 75% of the lymphatic drainage of the breast. The rest of the lymphatic drainage is derived from the medial aspect of the breast, through the internal mammary lymph nodes. Surgeons recognize six axillary lymph node groups divided into three levels. Level I lymph nodes are located lateral to the pectoralis minor muscle and include the axillary vein group, the external mammary group and the scapular group. Level II lymph nodes are located superficial and deep to the pectoralis minor muscle: the central group and the interpectoral group (Rotter's nodes). Level III lymph nodes are located medial to the pectoralis minor muscle and include the subclavicular group.

FEMALE GENITAL TRACT

Embryology

Approximately 10% of newborns present with a congenital anomaly of the genitourinary system (Vaughan and Middleton,1975). External gynecologic anomalies are most often apparent in infancy. The female genital tract is primarily derived from primitive mesoderm, while the germ cells are of endodermal origin, and the vulva and the epithelial lining of the vagina are of ectodermal origin (Robboy et al.,2002). In the early stages of development, the female and male genital systems are indistinguishable. Although genetic sex is determined at fertilization, it becomes clinically apparent at the twelfth week of embryonic life, where in the absence of fetal androgens, tissue differentiation leads to the external female phenotype.

Approximately 3 weeks after fertilization, the primordial germ cells migrate from the yolk sac to the urogenital ridges via the hindgut, at the tenth thoracic level (Robboy et al.,2002). On the medial surface of the urogenital ridge, the mesodermal epithelium begins to proliferate, resulting in the development of the epithelium of the gonad. In females, ovarian differentiation begins at approximately 8 weeks of gestational age, in the absence of testis-determining factor, which is found on the Y chromosome. The germ cells rapidly differentiate into 6–7 million oogonia by 16–20 weeks, and then they enter the first meiotic division as primary oocytes at which point they become arrested until puberty.

In 1830, Johannes Peter Muller was the first to describe the Müllerian (or paramesonephric) ducts. These paired ducts form lateral to the Wolffian (or mesonephric) ducts at approximately the sixth week of embryonic life, and grow caudally and medially, to eventually fuse in the midline in the third month of gestation. Under the influence of estrogen, the proximal portion of the Müllerian ducts differentiates into the fallopian tubes, and the distal portion forms the uterine body, cervix, and upper vagina. The fusion of the two Müllerian ducts brings together two peritoneal folds, which become the broad ligament. The Müllerian ducts eventually meet the urogenital sinus to form the sinusal tubercle. By the 20th week of fetal life, the uterine endometrium and myometrium is fully differentiated from the surrounding mesenchyme. Canalization of the paramesonephric ductal system creates the uterovaginal canal, which is complete by the 22nd week of gestation. The vaginal plate, a solid core of tissue of uncertain embryonic origin, eventually occludes the inferior portion of the uterovaginal canal. Over the subsequent 2 months, the vaginal plate gives rise to the vaginal epithelium. Estrogen also stimulates the wolffian ducts to form into the external female genitalia, including the lower vagina, labia, and clitoris.

Anatomy

Female External Genital Organs

The perineum can be conceptualized as a diamond-shaped space forming the outlet of the pelvis (Fig. 2). It is confined within the following boundaries: (1) anterolaterally, by the inferior margin of the pubic symphysis and the borders of the ischiopubic rami; (2) posterolaterally, by the coccyx and the sacrotuberous ligaments (covered by the gluteus maximus muscles); and (3) laterally, by the two ischial tuberosities. It can be subdivided into two triangles, the urogenital triangle anteriorly, and the anal triangle posteriorly. The urogenital triangle includes the external genital organs and the urethral opening, commonly referred to as the vulva.

Figure 2. Female external genitalia.

The vulva comprises the following structures:

• Mons pubis: Triangular eminence overlying the symphysis pubis, consisting of adipose and connective tissue.

• Labia majora: Located on either side of the vaginal opening, the labia majora are two fibroadipose skin folds extending from the mons pubis in a posterior direction, unite in the midline at the posterior fourchette. They include the terminal part of the round ligament and the obliterated processes vaginalis, also referred to as the canal of Nuck. They are approximately 7–8 cm in width and 1–2 cm thick. The labia majora are laterally covered by hair at and after puberty and are rich in sebaceous, apocrine, and eccrine glands. The subcutaneous tissue of the labia majora is similar in composition to the abdominal wall.

• Labia minora: Located immediately medial to the labia majora, the labia minora are two folds of hairless skin overlying a fibroelastic stroma rich in neurovascular structures, sebaceous follicles, a few sweat glands, and some smooth muscle. Anteriorly, the folds merge to form the hood of the clitoris, whereas posteriorly, they attach on the inferior surface of the clitoris to form the frenulum. The area between the posterior labia minora forms the vestibule of the vagina.

• Bartholin glands: Located on the posterolateral aspect of the vestibule, these glands measure approximately 0.5–1 cm and cannot normally be palpated. They secrete a colorless mucoid secretion between the hymen and the labia minora, mainly to maintain adequate lubrication.

• Clitoris: This erectile organ is normally 5 mm in length in prepubertal children, and 1–2 cm in length in mature females. It is the female counterpart of the penis, with a similar structure, including a glans, two crura, and two corpora cavernosa. It is located above the external urethral opening and is supported by a suspensory ligament that lies beneath the anterior labia commissure.

• Vestibule: The vestibule is bounded anteriorly by the clitoris and posteriorly by the opening of the urethra, the vagina, the ducts of Bartholin's glands, the ducts of the paraurethral (Skene's) glands and the fourchette.

• Vaginal orifice: The introitus lies posterior to the vestibule and is surrounded by the hymen, an incomplete mucous membrane which matures during puberty under the influence of estrogen, thereby becoming fuller and more elastic.

• External urethral meatus: Immediately anterior to the vaginal orifice, the urethral orifice is located about 2–3 cm posterior to the clitoris. The paraurethral (Skene's) gland ducts open on its posterior surface.

• Vestibular bulbs: These erectile bodies are highly vascular structures lying under the bulbocavernous muscle and the lining of the vestibule bilaterally. They are 3–4 cm long, 1–2 cm in wide, and 0.5–1 cm thick in mature females. They are covered by the ischiocavernosus muscle and are close to the ischiopubic rami.

• Muscles: Three muscles comprise the vulva, namely the ischiocavernosus, the bulbocavernosus, and superficial transverse perineal muscles.

Blood Supply, Innervation, and Lymphatic Drainage of the Vulva

The vascular supply to the vulva is mostly derived from the terminal branches of the internal pudendal vessels, which arises from the anterior division of the internal iliac artery. A rich anastomotic network links the internal pudendal vessels to the superficial and deep external pudendal vessels, which arise from the femoral artery.

The pudendal nerve, arising from the anterior rami of S2 to S4, provides the innervation to the lower vagina, labia, clitoris, perineal body, and their supporting structures. The ilioinguinal nerve (L1), the genital branch of the genitofemoral nerve (L1–L2), and the perineal branches of the posterior femoral cutaneous nerve (S1–S3) supply the mons pubis and upper labia.

The inguinal lymph nodes provide the primary lymphatic drainage of the vulva, urethra, and distal third of the vagina. The superficial inguinal lymph nodes, containing approximately 10 nodes, receive afferent channels from the labia and mons pubis. From there, the efferent channels drain into three to five deep inguinal lymph nodes located along the femoral vein. The most cephalad of these deep lymph nodes is referred to as Cloquet's node. Of note, only the midline vulvar components have bilateral lymphatic drainage.

Female Internal Genital Organs

• Vagina: This fibromuscular tubular structure extends from the vulvar vestibule to the uterus. It is bounded anteriorly by the bladder and urethra, and posteriorly by the rectum. The upper portion of the vagina is separated from the rectum by the cul-de-sac of Douglas (or rectouterine pouch). The vagina is oriented upward and posteriorly, forming a 60°–70° angle with the horizontal plane. The mature vagina has a diameter of 4–5 cm and a length of 8–10 cm. Its posterior wall is approximately 3 cm longer than its anterior wall. The vagina is composed of three layers: mucosa, muscularis and adventitia. The vaginal artery and branches from the uterine, middle rectal, and internal pudendal arteries provide the rich blood supply to the vagina. The uterovaginal plexus (S2–S4) innervates the upper portion of the vagina, while the terminal branches of the pudendal nerve supplies the distal vagina.

• Uterus: This fibromuscular organ can be divided into the lower cervix and upper uterine body. The uterus is composed of three layers: serous, muscular (myometrium), and mucous. The cervix is the region from the isthmus to its vaginal termination. It is divided into the portio vaginalis, which is exposed to the vagina, and the portio supravaginalis, which is immediately above. The vaginal portion (or exocervix) is convex, with a slitlike opening, the external cervical os. This opening is variable in size, depending on age and history of parturition. Proximal to the external cervical os is the endocervical canal, which terminates at the internal cervical os. The cervical mucosa is lined with stratified squamous epithelium in the exocervix, and mucin-producing columnar epithelium in the endocervical canal. The intersection where these two epithelia meet has a variable location and undergoes continuous change based on hormonal stimulation (Sokol et al.,2012).

• The uterine body varies in size and shape, under the hormonal influence and depending on childbearing status. At birth, the cervix is twice the length of the uterine body. At puberty this ratio inverses and in adult women, the uterine body is two to three times the size of the cervix. After menopause, the uterus atrophies. The isthmus, where the endocervical canal opens into the endometrial cavity, forms the uterine body along with the uterine cornu, which corresponds to the insertion of the fallopian tubes. The superior portion of the uterus is the fundus.

• Uterine Support Structures: There are three main support ligaments:

• The uterosacral and cardinal ligament complex is responsible for the normal orientation of the uterus and upper vagina and provides the major support to the uterus. It helps maintain the vaginal length and the horizontal vaginal axis in the upright position. The strong cardinal (or Mackenrodt) ligaments link the cervix and upper vagina to the side walls of the pelvis. The uterosacral ligaments are oriented posteriorly and inferiorly and attach to the ischial spine and sacrum, maintaining the uterus in anteversion.

• The round ligament originates at the uterine fundus, below the fallopian tubes. It originates from the embryonic female gubernaculum (Acien et al.,2011). It travels in the retroperitoneum through the layers of the broad ligament, enter the inguinal canal and attach to the labia majora. It provides accessory support to maintain the uterus in anteversion and anteflexion.

• The broad ligaments encompass the lateral uterine corpus and upper cervix. It encloses viscera, blood vessels and lymphatics in the retroperitoneum. They provide support to the uterus and the cervix.

• The uterine adnexa consist of the ovaries and fallopian tubes:

• Fallopian tubes: Extending bilaterally from the superior angles of the uterus, the fallopian tubes consist of the interstitial portion, the isthmus, the ampulla and the infundibulum (or fimbria), which opens into the abdominal cavity and is attached to the ovary. These paired tubular structures measure 7–12 cm in length and represent the proximal unfused ends of the Müllerian ducts. Their function includes ovum and sperm transport, as well as provision of a physical environment for conception.

• Ovaries: These paired structures are attached to the uterine cornua by the uteroovarian ligament, and to the hilum of the broad ligament by the mesovarium. Laterally, it is attached to the pelvic wall by the infudibulopelvic ligament, which protects the neurovascular bundles. The ovary varies in dimension with age, with each menstrual cycle, and under hormonal influence. Each ovary can be divided into the medulla and the cortex, and is covered by a single layer of flattened cuboidal cells on its outer surface. Follicles in various stages of development and attrition are located in the cortex. The ovarian medulla is primarily composed of fibromuscular tissue and blood vessels.

Blood Supply, Innervation and Lymphatic Drainage to the Uterus, Fallopian Tubes and Ovaries

The majority of the blood supply to the uterus, fallopian tubes, and ovaries is derived from the uterine and ovarian arteries. The retroperitoneal uterine arteries originate from the anterior division of the internal iliac arteries. The ovarian arteries arise from the abdominal aorta. Of note, the right ovarian vein empties in the inferior vena cava while the left ovarian vein returns to the left renal vein.

Only the ovaries and fallopian tubes are directly innervated by the preaortic plexus, which travels with the blood vessels. It originates in the renal plexus with fibers from the 10th thoracic level, and parasympathetic fibers from the vagus nerve (Sokol et al.,2012).

The internal genital organs receive both sympathetic and parasympathetic innervation. The sympathetic inferior hypogastric plexus consists of three areas: the vesical plexus, the uterovaginal plexus, and the middle rectal plexus. The uterovaginal plexus divides into anterior and posterior columns. The posterior column innervates the uterus, cervix, vagina, sigmoid colon and rectum. The parasympathetic input arises from S2 to S4.

The obturator, internal iliac, and external iliac lymph nodes provide the lymphatic drainage to the uterus and upper two-thirds of the vagina, and ultimately drain into the common iliac lymph nodes. The paraaortic lymph nodes receive afferent channels from the ovaries.

CONCLUSION

In-depth knowledge of normal embryology and anatomy provides the clinician with a reference point to understanding the basis of abnormal development and pathology of the breast and genital tract. A comprehensive understanding of anatomy is essential in the recognition and the multidisciplinary clinical evaluation, diagnosis, medical management, ablative surgery, and reconstruction of anomalies of the breast and female genital tract.