Effects of in utero exposure to dietary conjugated linoleic acid on mammary gland development in Balb/cJ mice

Conjugated linoleic acids (CLA) are isomers of octadecadienoic acid (18:2 n6) found in ruminant-derived food products, predominantly as cis-9, trans-11 CLA (9,11 CLA). Spreadable animal fat substitutes and weight loss supplements are generally mixtures of 9,11 CLA and trans-10, cis-12 CLA (10,12 CLA). These isomers have markedly different biological effects. Notably, 10,12 CLA intake reduces adiposity while inducing hepatic steatosis and insulin resistance. Both 9,11 CLA and 10,12 CLA have been proposed to afford anti-cancer properties given their ability to inhibit the growth of experimental cancers in vitro and in vivo. However, 10,12 CLA also enhanced mammary tumorigenesis in mice over-expressing the ErbB2 oncogene and mixed isomer supplementation increased tumor burden in mice that express polyoma virus middle-T antigen. These findings demonstrate the importance of resolving the effects of dietary CLAs on mammary gland (MG) development, particularly given their effects on metabolism. We therefore examined the effect of maternal intake of CLAs by studying the MG of female pups born to dams fed CLA during gestation. In one study, females were fed 1% 9,11 CLA or 1% 10,12 CLA throughout pregnancy. A subset of females was fed 10,12 CLA only during the first or second half of gestation. At birth, female pups born to these dams were cross-fostered onto dams fed the control diet during gestation. The MG of females exposed to CLA isomers in utero were analyzed at 21d, 35d, and 55d of age. Females exposed to 10,12 CLA in utero showed decreased (P<0.05) MG mass compared to control animals at 21d whereas there were no differences between progeny at 35d or 55d of age. Mass of the liver and uterus did not differ between treatment progeny at any time point. We subsequently investigated the effects of CLA exposure in utero on MG responsiveness to estrogen (E) and progesterone (P) either alone or in combination. Dams were fed either a control diet or that supplemented with 1% 9,11 or 1% 10,12 CLA during some or all of gestation, and female pups born to these dams were cross-fostered at birth onto foster dams fed the control diet. Pups were ovariectomized at 21d prior to the onset of puberty, and one week post-ovariectomy were treated with E, P, or E+P for 5 days. Mice were euthanized and their MG collected at 33d of age. Of the various maternal treatments, only female progeny exposed to 10,12 CLA demonstrated an increase (P<0.05) in MG mass following treatment with E. Results from these studies are significant in that they highlight how maternal intake of animal products such as dairy foods and weight loss supplements during pregnancy may impact postnatal development and hormone responses.

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