Organogenesis
During the fourth week of gestation, paired ectodermal thickenings, known as the mammary ridges or milk lines, form on the ventral surface of the embryo and extend in a curvilinear fashion from the axillae to the medial thigh.
In most mammals, paired breasts develop along these ridges, which extend from the base of the forelimb (future axilla) to the region of the hind limb (inguinal area). T
These ridges are not prominent in the human embryo and disappear after a short time, except for small portions that may persist in the pectoral region.
Accessory breasts (polymastia) or accessory nipples (polythelia) may occur along the milk line when normal regression fails.
These ridges eventually disappear except at the level of the fourth intercostal space on the anterior chest wall, where the mammary gland subsequently develops.
The earliest stages of embryogenesis are largely hormone independent; therefore, they occur in the same manner in both sexes.
During the fifth week of gestation, the remnant of the mammary ridge ectoderm begins to proliferate, forming the primary mammary bud. This subsequently begins growth downward as a solid diverticulum into the underlying dermis. By the 10th week, the primary bud begins to branch, yielding secondary buds by the 12th week, which eventually form the mammary lobules of the adult breast. The fatty tissues in the underlying mesoderm are considered to produce hormones and growth factors, which promote and regulate the growth of the developing mammary gland.
{Hormones and regulatory factors become important for development in the second trimester.]
During the remainder of gestation, the mammary buds continue lengthening and branching. By the 20th week, small lumina develop within the buds, which coalesce and elongate to form the lactiferous ducts. The canalization of the mammary buds is induced by progesterone, growth hormone, insulin-like growth factor, estrogen, prolactin, adrenal corticoids, and triiodothyronine. Approximately 15–20 lobes of glandular tissue are formed, each containing a lactiferous duct. The ducts drain into the retroareolar ampullae that converge into a depressed pit in the overlying skin. Stimulated by the inward growth of the ectoderm, the mesoderm surrounding this area proliferates, creating the nipple with circular and longitudinal smooth muscle fibers. The surrounding areola is formed by the ectoderm during the fifth month of gestation. The areola also contains other epidermal glands, including the glands of Montgomery (sebaceous glands that lubricate the areola).
At birth, the mammary glands have developed sufficiently in both sexes that they appear as distinct hemispheroidal elevations and are palpable as movable soft masses. This is especially prominent in postterm infants. Histologically, a number of branching channels with the layers of lining cells and plugs of basal cells at their ends (the future milk ducts and glandular lobules, respectively) can be easily recognized. In a great number of infants an everted nipple is observed, and in approximately 10% a greatly enlarged gland can be palpated. This condition has the unfortunate name of mastitis neonatorum, although no signs of inflammation exist. These early glandular structures may produce a milk-like secretion, the “witch’s milk,” starting 2 or 3 days after birth. All these neonatal phenomena in the breast are the result of the very intensive maternal estrogen-driven developmental processes in the last stages of intrauterine life. The changes subside within the first 2–3 weeks of life. It is during this period that the breast undergoes marked involutional changes leading to the quiescent stage, which is characteristic of infancy and childhood. During these periods the male and female glands consist of a few branching rudimentary ducts lined by flattened epithelium, surrounded by collagenous connective tissue.
For most girls the first sign of puberty is the appearance of breast budding. This early breast change begins at an average age of 10.8 (±1.1) years of age. At the onset of puberty and during adolescence, ovarian follicles ripen in response to follicle-stimulating hormone (FSH) of the anterior pituitary gland and estrogen output increases. In response to the latter, the mammary ducts elongate and the lining epithelium reduplicates and proliferates at the ends of the mammary tubules, forming the sprouts of the future lobules. This growth of ductal epithelium is accompanied by growth of periductal fibrous tissue, which is largely responsible for the increasing size and firmness of the adolescent female gland. During this period, the areola and nipple also grow and become more pigmented.
With the onset of maturity, that is, when ovulation occurs and the progesterone-secreting corpora lutea are formed, the second stage of mammary development occurs. It is essentially concerned with the formation of the lobules and acinar structures. While in the adult woman, progesterone always asserts its influence when estrogen is simultaneously present, overwhelming experimental evidence indicates that the initial unfolding of the lobules is a specific effect of progesterone. This gives the mammary gland the characteristic lobular structure found during the childbearing years. This differentiation into a lobular gland is finished approximately 1–1.5 years after the first menstruation, but further acinar development continues in proportion to the intensity of the hormonal stimuli during each menstrual cycle and especially during pregnancies. Fat deposition and formation of fibrous stroma contribute to the increasing size of the gland in the adolescent period.
Figure 4.1
The mammary milk line
Each breast develops when an ingrowth of ectoderm forms a primary tissue bud in the mesenchyme. The primary bud, in turn, initiates the development of 15 to 20 secondary buds. Epithelial cords develop from the secondary buds and extend into the surrounding mesenchyme. Major (lactiferous) ducts develop, which open into a shallow mammary pit. During infancy, a proliferation of mesenchyme transforms the mammary pit into a nipple. If there is failure of a pit to elevate above skin level, an inverted nipple results. This congenital malformation occurs in 4% of infants. At birth, the breasts are identical in males and females, demonstrating only the presence of major ducts. Enlargement of the breast may be evident and a secretion, historically referred to as witch’s milk, may be produced. These transitory events occur in response to maternal hormones that cross the placenta.
+++++++++++++++
[ completes its evolution during the postpartum lactation of the adult female.