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Mammary Gland Development
Prepubertal Period

Mammary Gland
Development During the
Prepubertal Period

Cross section of a 12 week old lamb's udder.

Acknowledgments: Paola Piantoni (Masters of Science, University of Illinois) contributed to the content of this page.

Birth to Puberty

[Also see: Sinha, Y.N. and H.A. Tucker. 1969.]

Mammary growth in the bovine is isometric (grows at the same rate as general body growth) for the first 2-3 mos. after birth. The duct system enlarges a little. The increase in udder size results from the continued increases in fat pad and connective tissue. At 30 d age, only a small portion of parenchyma (ca. 150 mg in the total gland), which is very difficult to dissect from the stroma, can be seen in the udder compartment. When the animal is 75 d age, the mass of parenchymal tissue becomes evident at palpation and at 90 d age, total parenchyma could weigh 10 g. No development of secretory alveoli occurs at this time.

At about 2 - 3 months after birth, allometric growth begins (growth rate faster than the rest of the body). In the calf, this includes extensive growth and development of the duct network which invades the surrounding adipose tissue (fat pad). No alveoli are formed. During pregnancy, the ducts will differentiate into milk secretory cells. Therefore, the formation of a duct network that occurs until puberty will determine the extent of lobulo-alveolar development during gestation. The allometric growth phase lasts until about 1 year of age, when the mammary growth rate returns to isometric growth. At this point, the mammary gland usually weights 2 to 3 kg, of which 0.5 to 1 kg is parenchymal tissue. The onset of puberty in heifers of large dairy breeds usually occurs at 9 to 11 mo age in animals weighing 250 to 280 kg on average, so this allometric growth phase continues for a short time beyond puberty. The allometric growth will not occur in the absence of the fat pad. There apparently are local interactions between the fat pad and the growing duct system, through the presence of cytokines and growth factors, but these interactions are not fully understood yet (see Autocrine and Paracrine Control of Mammary Growth).

The major portion of the mammary mass during the prepubertal period is the fat pad. Palpation of the gland from birth to 6 months of age is a poor predictor of the potential for future milk production in the mature animal. Other available methods to measure mammary gland growth include: tissue weight, tissue area, DNA content (indicative of cell numbers), incorporation of [3H] thymidine into DNA (indicative of cell division), RNA content (indicative of protein synthetic capacity), hydroxyproline (as a way of measuring connective tissue content), and total lipid content. Subsequent milk production could be related to these measurements. For example in heifers, the correlation between mammary DNA or RNA and subsequent milk production is low (~0.25). In rats, the correlation between mammary DNA and RNA at puberty and subsequent litter weight gains are 0.34 and 0.57, respectively.

This image is the cross-section of the udder of a 12 week old ewe lamb. The parenchmal tissue has been circled in red. The white areas are the fat pad. Note at the upper edge just left of the center of the gland is a dark area that is the supramammary lymph node. In studies of mammary growth of prepubertal ruminant species, usually it is the total mass of the parenchymal tissue that is measured. Cross-section of the udder of a 12 week old ewe lamb.

Effects of nutrition on mammary development

Milk production is a function of the amount produced by each secretory cell and the number of secretory cells in the mammary gland. Therefore, factors that determine the size of the epithelial cell population have an impact on milk production. Mammary growth is a complex process that can be affected by external influences such as nutrition and local influences such as hormones, growth factors, and cytokines.

Pre-weaning period (first 2-3 mo age; isometric growth)

Nutrition can stimulate greater rates of lean gain during the pre-weaning period, presumably without impairing future mammary development. Greater energy and protein intake to promote average daily gain of 0.66 kg/d during this period has the potential to increase mammary parenchymal mass, DNA and RNA amount, DNA concentration, and epithelial cell proliferation. This increase in energy and protein intake results in greater mammary development of 2-to-8 wk-old Holstein heifer calves, but does not stimulate additional growth of mammary parenchymal tissue in 8-to-14 wk-old calves (Brown et al., 2005a). In these older animals it only stimulates extra-parenchymal fat deposition. This shows that the preweaning period offers a window of opportunity to increase body growth rates through increased energy and protein intake without causing excess fattening.

Regarding future milk production in relation to different pre-weaning feeding programs, calves allowed to suckle a dam 3 ◊ day vs. calves fed a conventional milk replacer not only have greater ADG and wither height at the end of the feeding period (42 d), but also have earlier calving ages and a tendency for greater milk production at first lactation (Bar-Peled et al., 1997). Milk-fed calves (28.7% crude fat, 27% crude protein, two 30 min meals per day) reach puberty earlier, and produce more fat-corrected milk at first lactation when compared with milk replacer-fed calves (12% crude fat, 23% crude protein, fed at 450 g/d) (Shamay et al., 2005).

Commercial feeding programs with greater nutrient density are currently being used to obtain similar results in performance. Examples of these are the currently available intensified milk replacers. Intensified (28% crude protein, 20% fat; 2.0-2.5% BW adjusted weekly) vs. conventional (20% crude protein, 20% fat; 1.25% initial body weight) milk replacer programs have been related to greater milk production at first lactation (Drackley et al., 2008). Calves in this type of program, with increased feeding rate and protein to energy ratio, have greater growth rates and deposition of structural and lean tissues without additional fat deposition (Blome et al. 2003). Greater rates of lean gain during the pre-weaning period presumably will not impair mammary gland development (Brown et al., 2005a; Meyer et al., 2006a).

Pre-pubertal period (2-3 mo age to puberty; allometric growth)

Reduced performance during first lactation in heifers under a restricted or enhanced dietary program was observed as early as 50 years ago (Herman and Ragsdale, 1946; Swanson, 1960; see Johnson, in Feedstuffs, Oct. 20, 1986, for general review). This reduction was associated with impaired mammary development and excess fat deposition in the mammary gland compartment. Underfeeding during the prepubertal period also will decrease subsequent milk yield. But, the effect of overfeeding during the prepubertal period seems to be permanent. Heifers raised at a rapid growth rate prior to breeding have lowered percent of total mammary parenchymal tissue compared to those raised at a more modest rate of growth (see Harrison et al., 1983).

Nevertheless, increased body fatness rather than ADG is being considered a better predictor of impaired mammary development (Silva et al., 2002). This increased body fatness could result in more adipose deposition in the mammary gland, less mammary parenchymal tissue, and sometimes, lower milk production. It also has been suggested that if reduced mammary development is responsible for the reduction in milk yield, it is because the heifers under the high-plane of nutrition have a shorter allometric mammary growth period because they reached puberty earlier (Van Amburgh et al., 1998). Variation in parenchymal development is more related to age at harvest than to level of nutrient intake (Meyer et al., 2006a). This could be another way to understand why mammary development is impaired by high-feeding level in prepubertal heifers.

To evaluate the effect of nutrition on mammary development at this stage, Sejrsen et al. (1982) evaluated the mammary gland of pre-pubertal and postpubertal heifers that were fed 60:40 concentrate:roughage, either ad libitum or restricted to 60% of ad lib.. Feed restricted heifers average daily gain was 613 g vs. 1218 g for ad lib. Animals were slaughtered at 320 kg for the prepubertal group and 440 kg for the postpubertal group (prepub. heifers were actually slaughtered after puberty). Results were:

- Ad libitum feeding in the prepubertal group decreases mammary parenchymal tissue weight by 23% and decreases mammary DNA by 32% compared with the feed restricted group. Feeding level has no effect on postpubertal heifers. Composition of mammary parenchyma is not affected by plane of nutrition.

- Serum concentrations of prolactin, insulin and glucocorticoids are higher in the ad libitum heifers for both the pre- and postpubertal heifers (Sejrsen et al., 1983). However, growth hormone is increased in the prepubertal heifers on the restricted feed compared with the ad lib. group, but there is no difference in GH levels in the postpubertal groups. Mammary parenchymal tissue is positively correlated with GH levels. Mammary parenchymal tissue is negatively correlated with mammary adipose tissue.

Manipulation of heifer growth rates at optimal times by nutrition and or administration of somatotropin can enhance mammary development and lactation (see Park et al. 1987; Carstens et al. 1997). The effects of nutrition and BST do not seem to be additive.

Overfeeding beef heifers also can reduce subsequent milk production (Buskirk et al, 1996). Administration of bovine somatotropin to prepubertal beef heifers does not overcome the deleterious effects of high dietary energy on mammary development.

In prepubertal lambs (McFadden et al., 1990) plane of nutrition does not affect mammary parenchymal development; however, supplemental dietary lipid (polyunsaturated fat) increases mammary development. Both the size of the fat pad and the lipid composition of the fat pad may be influencing the extent of mammary development during the prepubertal period, however, dietary fatty acid composition is considered to have little or no effect on mammary development in cattle.

Influence of growth hormone and leptin on mammary development.

Daily injection of somatotropin (growth hormone) to heifers from 8 to 15.6 months of age resulted in increased mammary parenchyma and decreased extraparenchymal tissue compared to controls (see Sejrsen et al., 1986). Growth hormone stimulates mammary growth through increasing the hepatic synthesis of insulin-like growth factor-1 (IGF-1), which is a potent mitogen for mammary cells. Therefore, growth hormone may be a major factor in the control of mammary development during the prepartum period. However, growth hormone administration during the prepubertal period does NOT seem to increase milk yield during the first lactation (see Grings et al. 1990; Murphy et al. 1991 J. Dairy Sci. 74:2165).

Another protein that influences mammary development indirectly and that could explain how excessive fattening could cause mammary impairment is leptin, which is produced by adipocytes and decreases IGF-1-induced bovine mammary cell proliferation in vitro (Silva et al., 2002). In vitro studies suggest that leptin could not mediate the effects of a high-plane of nutrition by acting directly on mammary epithelial cells in prepubertal heifers due to almost non-existent leptin receptor expression in those cells (Thorn et al., 2006). However, in vivo studies demonstrate the above-mentioned effect of leptin on mammary cell proliferation (Silva et al., 2008). Leptinís influence on mammogenesis also could be mediated by inhibition of the IGF-1 signaling through stimulation of other cells found in the mammary gland, such as macrophages. For example, upon stimulation and in the presence of leptin, macrophages will increase their phagocytic activity and production of cytokines such as TNF? and IL-6 (Loffreda et al., 1998; Matarese et al., 2005), which have been associated with inhibition of IGF-1-induced proliferation in other cell types (Shen et al., 2004).

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