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Communication Dans Un Congrès Année : 2011

Long-term effects of nutrition on mammary gland development and milk composition leading to offspring predisposition to obesity

Résumé

Mammary epithelial growth and differentiation are tightly modulated by several hormonal and metabolic signals (Hennighausen and Robinson, 2005). Altered nutrition, leading to differences in the body weight, during the major developmental steps of this organ may be of critical importance (Sejrsen, 1994). In order to understand the impact of nutrition on mammary gland development and lactation, changes to the nutritional status of various animal models have been made in order to alter the metabolic environment. In cattle, an increased growth rate due to a high feeding level during puberty has been shown to reduce mammary epithelial cell proliferation in areas of active ductal expansion and thus limit mammary development and subsequent milk potential (Davis Rincker et al., 2008; Sejrsen et al., 2000). The effects of obesity on lactogenesis have also been demonstrated in the rat, where this pathology was shown to affect the chances of a successful outcome to pregnancy and lactation (Rolls et al., 1984). Similarly, in mice, diet-induced obesity resulted in lactation failure. More specifically, obese mice displayed marked abnormalities in alveolar development of the mammary gland during pregnancy, together with a marked decrease in major milk protein expression (Flint et al., 2005). Moreover, during earlier stages of development (puberty), obesity was shown to disrupt mammary ductal growth by reducing the branching frequency and width of ducts (Kamikawa et al., 2009). In humans, obesity is considered to be a major worldwide health issue and a predisposing risk for the morbidity of type 2 diabetes, hypertension and cardiovascular diseases. Obesity has also been strongly correlated with an increased risk of mammary tumorigenesis (Stoll 2000). Furthermore, in the United States, Chapman and Pérez-Escamilla noted that women who were overweight or obese at the time of childbirth were at significant risk of failing to initiate successful lactation, or were no longer breastfeeding at two days postpartum (Chapman and Perez-Escamilla, 1999). Similarly, a European study of obese women (BMI >26 kg/m2) found an association between obesity and an early cessation of breastfeeding (Riva et al., 1999) and a decrease in the normal prolactin response to suckling (Rasmussen and Kjolhede, 2004). We have further investigated the impact of obesity on mammary gland development. During this study, we used a model of rabbits receiving an obesogenic diet (OD rabbits), starting before puberty and extending until midpregnancy. At mid pregnancy we have shown that the body weight of OD animals was significantly higher than that of animals fed the control diet (C rabbits) and their mammary glands displayed a precocious and abnormal development at mid-pregnancy. These results support the critical influence of nutrition on mammary growth and differentiation, which may be deleterious to subsequent lactation. We have recently studied lactation of those animals. Milk production was equivalent between the two groups. However, lipid content of milk was 6-fold increased in OD rabbits. Moreover milk leptin concentration was significantly higher in OD animals. The growth of the offspring was not altered until weaning, but pups fed with OD milk and receiving an OD diet (OD/OD rabbits) exhibit a further increase in the body weight as compared to those fed control milk and the same OD diet (C/OD rabbits). Moreover, OD/OD females had on Day 8 of pregnancy an abnormal development of the mammary gland. Secretory tissue was scarce, embedded in adipose tissue and presented huge luminal structures filled with dense products. Lactation of these females is currently under study. Results will provide an insight on effects of maternal obesity on lactation and on growth of their offspring. They might thus lead to breastfeeding recommendations to obese women.
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Dates et versions

hal-01000196 , version 1 (04-06-2014)

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  • HAL Id : hal-01000196 , version 1
  • PRODINRA : 48717

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Emmanuelle E. Koch, Catherine Hue-Beauvais, Pascale Chavatte-Palmer, Etienne E. Aujean, Michèle Dahirel, et al.. Long-term effects of nutrition on mammary gland development and milk composition leading to offspring predisposition to obesity. 8. International Symposium on Milk Genomics & Human Health, Nov 2011, Melbourne, Australia. 1 p. ⟨hal-01000196⟩
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