Dietary supplementation with lysine (protein) in late pregnancy does not enhance mammary development in multiparous sows.

This project was conducted to determine if providing standardized ileal digestible (SID) Lys at 40% above estimated requirements (NRC, 2012), with the concomitant increased protein intake, from days 90 to 110 of gestation stimulates mammary development in multiparous sows. From day 90 of gestation, Yorkshire × Landrace multiparous sows (parities 2 and 3) were fed 2.6 kg/d of either a conventional diet (CTL, control, n = 17) providing 14.8 g/d of SID Lys or a diet providing 20.8 g/d of SID Lys via additional soybean meal (HILYS, n = 16). The diets were isoenergetic. Concentrations of IGF-1, glucose, free fatty acids (FFA), urea, and amino acids (AA) were measured in jugular blood samples obtained on days 90 and 110 of gestation. Sows were necropsied on day 110 ±â€…1 of gestation to obtain mammary glands for compositional and histological analyses. Backfat or BW changes of sows during late gestation were unaffected by treatment (P > 0.10), as was the case for fetal BW (P > 0.10). None of the variables measured in mammary tissue were altered by supplementary Lys (P > 0.10). Circulating IGF-1, glucose, and FFA did not differ (P > 0.10) between HILYS and CTL sows on day 110 of gestation, whereas concentrations of urea were greater (P < 0.01) in HILYS versus CTL gilts. Concentrations of Ile and Thr in plasma were also greater (P < 0.05), and those of Glu were lower (P < 0.01) in HILYS than CTL sows. These results demonstrate that feeding Lys (via protein) above current NRC recommendations during late gestation does not improve mammary development of multiparous sows. Hence, the use of a two-phase feeding strategy to provide more Lys (protein) to multiparous sows during this period is not necessary.

Results indicate that there is no advantage in terms of mammary development to feeding late-pregnant multiparous sows with 40% more lysine (via protein) than current recommendations (NRC, 2012). From days 90 to 110 of gestation, multiparous sows (parities 2 and 3) were fed 2.6 kg/d of either a conventional diet providing 14.8 g/d of standardized ileal digestible (SID) lysine or a diet providing 20.8 g/d of SID lysine via the inclusion of additional soybean meal. Diets were isoenergetic. Feeding supplementary SID lysine had no effect on mammary development at the end of gestation. Contrary to our previous report for gilts, mammary gland development is not improved by providing more lysine to multiparous sows in late gestation. Such information is crucial for developing the best feeding strategies to maximize milk yield. The use of a two-phase feeding strategy to provide more lysine (protein) as of day 90 of gestation is not necessary in multiparous sows.

Dietary supplementation with lysine (protein) stimulates mammary development in late pregnant gilts.

The goal of this project was to determine if standardized ileal digestible (SID) lysine provided at 40% above estimated requirements, with the concomitant increase in protein intake, from days 90 to 110 of gestation would stimulate mammary development in gilts. From day 90 of gestation, Yorkshire × Landrace gilts were fed 2.65 kg of either a conventional diet (CTL, control, n = 19) providing 18.6 g/d of SID Lys or a diet providing 26.0 g/d of SID Lys via additional soybean meal (HILYS, n = 19). Both diets were isoenergetic. Jugular blood samples obtained on days 90 and 110 of gestation were used to measure concentrations of insulin-like growth factor-1 (IGF-1), metabolites, and amino acids (AA). Gilts were necropsied on day 110 ± 1 of gestation to obtain mammary glands for compositional analyses, immunohistochemistry, and analysis of mRNA abundance for AA transporters and markers of cell proliferation and differentiation. The HILYS gilts gained more body weight (P < 0.01) during the experimental period compared with CTL gilts, and had greater fetal weights (1.29 vs. 1.21 ± 0.03 kg, P < 0.05). There was no difference in circulating IGF-1, glucose, or albumin (P > 0.10) between HILYS and CTL gilts on day 110 of gestation, whereas concentrations of urea and free fatty acids were greater (P < 0.01), and those of Trp and Ala were lower (P < 0.05), in HILYS than CTL gilts. The provision of lysine at 40% above estimated requirements increased total mammary parenchymal mass by 44%, as well as total parenchymal fat, protein, DNA, and RNA (P < 0.01). The mRNA abundance of ACACA was greater (P < 0.05) in HILYS than CTL gilts, while only the AA transporter SLC6A14 tended (P < 0.10) to be greater. Results demonstrate that providing dietary Lys above current National Research Council recommendations in late gestation increases mammary development in gilts. Results also indicate that Lys may have been limiting for protein retention. These data suggest that the use of a two-phase feeding strategy during gestation, whereby dietary Lys is increased from day 90, could benefit potential sow milk yield in the subsequent lactation.

Results indicate that the current National Research Council recommendations for dietary lysine during late pregnancy in pigs, the period when most mammary gland development takes place, are underestimated. From days 90 to 110 of gestation, gilts were fed 2.65 kg of either a conventional diet providing 18.6 g/d of standardized ileal digestible (SID) lysine, or a diet providing 26.0 g/d of SID lysine via the inclusion of additional soybean meal. Diets were isoenergetic. Feeding 26.0 g/d of SID lysine increased the mass of mammary parenchymal tissue (where milk is synthesized) by 44%. Findings suggest that a greater mammary uptake of lysine in supplemented sows supported enhanced accretion of mammary parenchyma. Such information is most pertinent in the actual context where milk yield of hyperprolific sows must be maximized to sustain optimal growth of all their piglets. Furthermore, these data indicate that the use of a two-phase feeding strategy during gestation, whereby dietary lysine is increased from day 90, could benefit potential sow milk yield in the subsequent lactation.

Folate Deficiency Inhibits Development of the Mammary Gland and its Associated Lymphatics in FVB Mice.

BACKGROUND: Folate is essential for DNA synthesis, DNA repair, cell proliferation, development, and morphogenesis. Folic acid (FA) is a nutritional supplement used to fortify human diets. OBJECTIVES: We investigated the effects of dietary FA on early mammary gland (MG) development and hyperplasia. METHODS: Study 1: nulliparous female FVB wild-type (WT) mice were fed control (Con; 2 mg FA/kg), deficient (Def; 0 mg FA/kg), excess (Ex; 5 mg FA/kg), or super excess (S-Ex; 20 mg FA/kg) diets for 8 wk before mating to WT or heterozygous FVB/N-Tg[mouse mammary tumor virus long terminal repeat (MMTV)-polyomavirus middle T antigen (PyVT)]634Mul/J (MMTV-PyMT+/-) transgenic males. Dams were fed these diets until they weaned WT or MMTV-PyMT+/- pups, which were fed the dam's diet from postnatal day (PND) 21 to 42. Tissues were collected from female progeny at PNDs 1, 21, and 42. Study 2: Con or Def diets were fed to WT intact females and males from PND 21 to 56, or to ovariectomized females from PND 21 to 77; tissues were collected at PND 56 or 77. Growth of all offspring, development of MGs, MG hyperplasia, supramammary lymph nodes, thymus and spleen, cell proliferation, and expression of MG growth factors were measured. RESULTS: Study 1: Ex or S-Ex did not affect postnatal MG development or hyperplasia. The rate of isometric MG growth (PND 1-21) was reduced by 69% in Def female progeny (P < 0.0001). Similarly, hyperplastic growth in MGs of Def MMTV-PyMT+/- offspring was 18% of Con (P < 0.05). The Def diet reduced supramammary lymph node size by 20% (P < 0.0001) and increased MG insulin-like growth factor 2 mRNA by 200% (P < 0.05) and protein by 130%-150% (P < 0.05). Study 2: the Def diet did not affect MG growth, but it did reduce supramammary lymph node size (P < 0.05), spleen weight (P < 0.001), and thymic medulla area (P < 0.05). CONCLUSIONS: In utero and postnatal folate deficiency reduced the isometric development of the MGs and early MG hyperplasia. Postnatal folate deficiency reduced the development of lymphatic tissues.

Trans-Fatty Acid-Stimulated Mammary Gland Growth in Ovariectomized Mice is Fatty Acid Type and Isomer Specific.

We previously reported that the trans-18:2 fatty acid trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulates mammary gland development independent of estrogen and its receptor. Given the negative consequences of dietary trans-fatty acids on various aspects of human health, we sought to establish whether other trans-fatty acids could similarly induce ovary-independent mammary gland growth in mice. Prepubertal BALB/cJ mice were ovariectomized at 21 days of age then were fed diets enriched with cis-9, trans-11 CLA (c9,t11-CLA), or mixtures of trans-18:1 fatty acids supplied by partially hydrogenated sunflower, safflower, or linseed oil. The resultant mammary phenotype was evaluated 3 weeks later and compared to the growth response elicited by t10,c12-CLA, or the defined control diet. Whereas partially hydrogenated safflower oil increased mammary gland weight, none of the partially hydrogenated vegetable oils promoted mammary ductal growth. Similarly, the c9,t11-CLA supplemented diet was without effect on mammary development. Taken together, our data emphasize a unique effect of t10,c12-CLA in stimulating estrogen-independent mammary gland growth manifest as increased mammary ductal area and elongation that was not recapitulated by c9,t11-CLA or the partially hydrogenated vegetable oil diets.

Diet-induced metabolic change induces estrogen-independent allometric mammary growth.

Lifetime breast cancer risk reflects an unresolved combination of early life factors including diet, body mass index, metabolic syndrome, obesity, and age at first menses. In parallel, the onset of allometric growth by the mammary glands around puberty is widely held to be estrogen (E)-dependent. Here we report that several physiological changes associated with metabolic syndrome in response to a diet supplemented with the trans-10, cis-12 isomer of conjugated linoleic acid lead to ovary-independent allometric growth of the mammary ducts. The E-independence of this diet-induced growth was highlighted by the fact that it occurred both in male mice and with pharmacological inhibition of either E receptor function or E biosynthesis. Reversal of the metabolic phenotype with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone abrogated diet-induced mammary growth. A role for hyperinsulinemia and increased insulin-like growth factor-I receptor (IGF-IR) expression during mammary growth induced by the trans-10, cis-12 isomer of conjugated linoleic acid was confirmed by its reversal upon pharmacological inhibition of IGF-IR function. Diet-stimulated ductal growth also increased mammary tumorigenesis in ovariectomized polyomavirus middle T-antigen mice. Our data demonstrate that diet-induced metabolic dysregulation, independently of ovarian function, stimulates allometric growth within the mammary glands via an IGF-IR-dependent mechanism.