Epidemiological and animal studies suggest that alterations to the hormonal and metabolic environments during puberty can induce both adverse effects on lactation and mammary tumorogenesis (de Assis et al, 2006). Obese women have an increased risk of failing to initiate successful breastfeeding and can experience a premature cessation of lactation (Riva et al, 1999; Rasmussen et al, 2004). The effects of obesity on lactogenesis were highlighted during early studies in the rat, where this pathological condition was shown to reduce the chances of a successful outcome regarding pregnancy and lactation (Rolls et al, 1984). More recent studies have suggested that impaired mammary gland development and lactogenesis are possible causes of lactation failures and the high mortality observed amongst the pups of obese dams. In cattle, evidence concerning the relationship between growth rate, mammary growth and milk yield led to the conclusion that increased growth rate due to high feeding levels before the onset of puberty could reduce pubertal mammary development and milk potential (Sejrsen, et al, 1997). Moreover, high energy feeding decreases mammary epithelial cell proliferation in areas of active ductal expansion at puberty (Davis Rinker et al, 2008). We have further investigated the impact of obesity on mammary gland development. A rabbit model of diet-induced obesity was developed by feeding female rabbits with a high fat (HF) diet (+276% fat and +269% sugar when compared to the control (C) diet) from 8 weeks of age until mid-pregnancy (day 14 of pregnancy). Body weight gain between 21 weeks of age until day 14 of pregnancy was significantly higher (+10%) in HF animals, and was mainly associated with the development of more adipose tissue. By contrast, the number of fetuses did not differ between the two groups, although mean fetal weight was lower in HF rabbits than in controls. Mammary gland morphology was altered in the HF group. On day 14 of pregnancy, the mammary ducts were made up of a cell monolayer. They were dilated and filled with dense products. Alveolar structures had invaded the entire fat pad, whereas they were more clustered in the control group. Electron microscopy analysis revealed that casein micelles were present in the lumen of alveolae. Moreover, numerous microvillosities were located in the apical region of mammary epithelial cells. Immunohistochemical studies of HF mammary tissue revealed a more abundant accumulation of the major rabbit milk proteins, alphaS1-casein, kappa-casein and Whey Acidic Protein (WAP), in both the alveolar lumina and secretory ducts. As revealed by BodiPy staining, lipids had also accumulated in the lumens and ducts. Both analyses revealed an early secretory phenotype in the HF group. Milk protein synthesis in mammary tissue extracts was quantified by Western blot analyses. A clear accumulation of milk proteins was observed in HF animals but was almost undetectable in controls. These results show that diet-induced obesity, beginning before puberty, alters mammary gland development at mid-pregnancy in the rabbit. On day 14, obese mammary tissue displayed a morphological aspect and functional profile similar to those normally observed at the end of pregnancy. In rodents, similar precocious mammary development induced by WAP overexpression (Burdon et al, 1991) or the constitutive activation of PRL transduction pathways (Gourdou et al, 2004) have been associated with impaired lactation, so that lactation defects could be anticipated in HF animals. The effects on lactation of this early development are currently under study.