ARS | Publication request: Lactation persistence is enhanced in transgenic mice overexpressing des(1-3)hIGF-I in the mammary gland

Submitted to: Journal of Animal Science Supplement
Publication Type: Abstract Only
Publication Acceptance Date: March 1, 2004
Publication Date: May 1, 2004
Citation: Hadsell, D.L., Torres, D.T., George, J., Shelton, G.S., Fiorotto, M.L. 2004. Lactation persistence is enhanced in transgenic mice overexpressing des(1-3)hIGF-I in the mammary gland [abstract]. Journal of Animal Science Supplement. 82(Suppl. 1):204.

Technical Abstract: Transgenic overexpression of IGFs within the mammary gland during lactation delays involution and inhibits apoptosis. The goals of this study were: 1) to determine if mammary apoptosis was associated with increased oxidative damage and decreased milk yield during prolonged lactation, and 2) to test the hypothesis that overexpression of des(1-3)hIGF-I within the mammary glands of transgenic mice (WAP-DES) would increase lactation persistence. Mammary morphology, apoptosis, proliferation, and protein carbonyl content were compared among normal mice (N=3-13) during early and prolonged lactation. Persistence was compared among nontransgenic (N=9) and WAP-DES (N=13) mice by measuring the weight gain of cross-fostered litters (10 pups/litter) from day 14 to 35 postpartum. Apoptosis and proliferation were measured using immunohistochemical markers. Proliferation was highest on day 2 (6.3±0.5 and 18.3±1.8 % for phospho-histone H3 and BrdU, respectively) decreased dramatically on day 3 (1.8±0.5 and 3.1±2.0 %, respectively), and remained low throughout the rest of lactation. Apoptosis was low throughout lactation (0.3±0.04 and 0.1±0.01 % for TUNEL and active-caspase 3, respectively). Protein carbonyl content, as measured by dinitrophenyl-hydrazine reactivity, peaked on day 2 postpartum (0.4±0.2 nmole/mg), decreased on day 5 (0.2±0.1 nmole/mg), and remained low through the rest of lactation. Litter gain dropped in both nontransgenic and WAP-DES mice beginning on day 21 postpartum. By day 35, litter gain was 6.6±2.6 and –2.4±2.7 gm/wk for the WAP-DES and nontransgenic mice, respectively. Mammary gland wet weight at day 35 was also greater in WAP-DES mice than their nontransgenic counterparts (448±24 and 346±25 mg, respectively). Milk composition, however, was similar among genotypes. These data support the conclusion that neither increased apoptosis nor oxidative damage is responsible for declining milk yield during prolonged lactation. The data also support the conclusion that overexpression of des(1-3)IGF-I allows for the maintenance of a greater mammary tissue mass and enhanced lactation persistence.