Developmental and Nutritional Regulation of the Prepubertal Bovine Mammary Gland: II. Epithelial Cell Proliferation, Parenchymal Accretion Rate, and Allometric Growth

Abstract

It is well documented that elevated nutrient intake prior to puberty reduces prepubertal mammary development in the bovine. The companion paper demonstrated that age at harvest is a primary determinant of parenchymal (PAR) mass and that any effects of elevated energy intake on mechanisms regulating mammary development are dwarfed by this effect of time. Therefore, it is hypothesized that while causing a decrease in prepubertal PAR mass, elevated nutrient intake will have no effect on growth characteristics of the mammary gland. The objectives of this experiment were to evaluate the effects of increased nutrient intake from early in life on 1) mammary epithelial cell proliferation, 2) mammary PAR DNA accretion rates, and 3) the dynamics of prepubertal allometric PAR growth. Holstein heifers (n = 78) were fed from 45 kg of body weight either elevated (E) or restricted (R) levels of nutrients to support 950 (E) or 650 (R) g/d of body weight gain. Six heifers per treatment were harvested at 50-kg increments from 100 to 350 kg of body weight. Heifers on the E plane of nutrition had higher plasma leptin and less PAR DNA than their body weight-matched R-intake cohorts. Despite this reduction in PAR DNA, treatment did not negatively influence mammary epithelial cell proliferation or the PAR DNA accretion rate. Dynamics of allometric and isometric mammary growth were also unaffected by the level of nutrient intake, as was exit from allometric growth. This work represents the first demonstrating that the level of nutrient intake and the concomitant increase in plasma leptin have no measurable influence on 1) the rate of PAR DNA accretion, 2) mammary epithelial cell proliferation, or 3) total PAR mass and, by default, the local or systemic controls that coordinate these processes.

The effect of calf nutrition on the performance of dairy herd replacements

“…However, Meyer et al (2006a) having examined heifers at up to 350 kg found no effect of increased nutrient intake on mammary parenchyma DNA content concluding that age at which mammary samples are taken, and not level of nutrient intake, was the main determinant of pre-pubertal mammary development. Subsequent follow-up studies found minimal effects of elevated levels of nutrition on the expression of a number of genes (Meyer et al, 2007), mammary epithelial cell proliferation or the rate of parenchyma DNA accretion (Meyer et al (2006b). Shamay et al (2005), Bar-Peled et al (1997) and Drackley et al (2007) are the only studies to find a significant positive relationship between level of pre-weaning nutrition and subsequent milk production.…”

Bovine mammary stem cells: cell biology meets production agriculture

“…Proliferation of EC occurs throughout the TDU, with the greatest rates of growth at the periphery of the TDU and periphery of the gland (Capuco et al, 2002a). Pre-and post-pubertally, there is a progressive increase in the ductal structures upon which alveoli develop during pregnancy (Sinha and Tucker, 1969;Sejrsen et al, 1982;Meyer et al, 2006a). The ability to regulate MaSC, and in turn mammary epithelial growth, may promote increased mammary development during the prepubertal period or may provide a means to reduce or eliminate possible negative impacts of increased nutrition prepubertally.…”

“…Reasons for selection of this physiological state are several-fold: (1) The rate of proliferation in the prepubertal mammary gland is impressive. The epithelial 5-bromo-2 0 -deoxyuridine (BrdU)-labeling index (fraction of EC labeled following a pulse labeling period with BrdU) within the peripheral TDU was found to be approximately 10% (Capuco et al, 2002a), declining as the heifer nears puberty (Meyer et al, 2006a). (2) It was reasoned that at this early stage of mammary development, MaSC and progenitor cells would be relatively abundant and active (Capuco et al, 2002a) considering the need for both symmetric and asymmetric divisions to provide for duct elongation and lineage differentiation (Ellis and Capuco, 2002;Meyer et al, 2006a).…”

“…The epithelial 5-bromo-2 0 -deoxyuridine (BrdU)-labeling index (fraction of EC labeled following a pulse labeling period with BrdU) within the peripheral TDU was found to be approximately 10% (Capuco et al, 2002a), declining as the heifer nears puberty (Meyer et al, 2006a). (2) It was reasoned that at this early stage of mammary development, MaSC and progenitor cells would be relatively abundant and active (Capuco et al, 2002a) considering the need for both symmetric and asymmetric divisions to provide for duct elongation and lineage differentiation (Ellis and Capuco, 2002;Meyer et al, 2006a). (3) The prepubertal mammary gland is very sensitive to the important mammary mitogen, estrogen (Capuco et al, 2002a;Berry et al, 2003;Connor et al, 2007), and it is important to understand the relationship between estrogenic stimuli and MaSC/progenitor cell proliferation (Sleeman et al, 2007).…”

“…However, increased level of nutrition before weaning may be positively correlated with mammary growth and milk production (Bar-Peled et al, 1997;Brown et al, 2005;Meyer et al, 2006a and2006b) or at least without negative impact (Daniels et al, 2009). Much of the epithelial growth during this stage involves penetration of the mammary fat pad by the mammary ducts.…”