lecture 4

• growth is the increase in size/mass
• growth can be described by 2 terms: hyperplasia and hypertrophy
• hyperplasia is an increase in cell number
• hypertrophy is the increase in cell size
• development describes less specialized structures becoming more specialized for a specific function (like the mouse paw losing cells to become a more developed foot)
• isometric growth describes an organ or tissue growing at the same rate as the rest of the body
• allometric growth describes the disproportionate growth of organs (faster) compared to the rest of the body
• mammogenesis is the formation/growth/development of mammary tissues/glands
• mammary growth and development first begins in an embryo
• embryonic and fetal growth and development occurs in utero
• pre-weaning, pre-pubertal, pubertal, and pregnancy growth and development occurs post-natal
• the ectoderm gives rise to mammary epithelium (parenchyma); nerves
• the mesoderm gives rise to mammary stromal tissues; includes fibrous and elastic connective tissues, adipose tissue, blood and lymph vessels, and the fat pad
• the endoderm does not contribute to mammary tissues
• the 6 stages of embryonic mammary development: band, streak, line, crest, hillock, and bud
• in embryonic mammary development, accumulation of proliferating cells occurs and form a thick band that slowly gets more concentrated; eventually the distal ends are lost and the cells form a hillock shape; hyperplasia concentrates the cells in a specific region until a bud is formed
• there is one mammary bud per gland/teat
• the crown-rump length of fetus directly correlates to the days of gestation
• most mammary formation concludes at 180 days gestation; after this continued growth occurs
• 6 stages of fetal development: 1. early teat formation (from bud), 2. primary sprout, 3. secondary sprout, 4. canalization of primary sprout, 5. development of gland and teat cistern, 6. development of median suspensory ligament
• the fat pad originates from the mesoderm
• competition for space causes pressure on the bud leading to extrusion to form a papilla or primitive teat
• canalization is the opening of the primary sprout by controlled cell death (apoptosis) and cell migration
• keratin keeps the teat closed for awhile since it does not need to be fully developed during canalization of the primary sprout
• after development of key structures, the mammary gland only grows; growth is slowed as key structures exist and are relatively established; the fat pad enlarges, parenchyma (sprouts) may increase in size, support structures become more competent; all relatively slow
• at birth, the teat, teat cistern, streak canal, gland cistern, primary and secondary sprouts, median suspensory ligament, and mammary fat pad are present
• at birth, the mammary structures have no secretory epithelium and is not organized
• the parenchyma grows at a faster rate than the fat pad
• at pregnancy, the alveoli begin to develop and are not fully developed until the end of pregnancy; in response to hormonal stimuli (estrogen, progesterone, and somatotropin)
• parenchyma expands dorsally into the fat pad
• the terminal ductal unit is where growth/development occurs in the parenchyma
• pre-weaned mammary growth (months 1-3): mass of parenchyma accrues above teat; grows 20x its size, growth responds to nutrition, can have long term effects on future milk yield
• mammary growth mostly stops at puberty
• pre-pubertal mammary growth: no complex organization, ducts are simply lengthening (branching and expanding into the fat pad); lack of complex development because needs to prepare/be ready for future lactation
• the mammary gland's purpose is to nourish the neonate; pregnancy is the main driver
• pubertal mammary growth (months 9-12): ovaries become active, estrus cycle begins, mammary growth and development becomes hormone driven (estradiol and progesterone)
• estradiol and progesterone concentrations are inversely related; rapid mammary growth is only promoted when they are both equal/high during luteolysis
• estradiol and progesterone stimulates epithelial cell proliferation and development of alveoli
• estradiol/paracrine signaling: estradiol is a steroid hormone, that can enter a cell to bind to a receptor to produce EGF, amphiregulin, and IGF-1, which are all protein hormones that bind to extracellular receptors on neighboring cells to cause proliferation
• progesterone signaling: progesterone is also a steroid hormone that can enter a cell to bind to a receptor, which then creates Wnt-4, which is a protein hormones that can bind to neighboring cells to cause proliferation and branching