Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin

Saad, H. El Sheikh; Méduri, G.; Phrakonkham, Pham; Berges, Raymond; Vacher, Sophie; Djallali, M.; Auger, Jacques; Canivenc-Lavier, Marie-Chantal; Perrot‐Applanat, Martine

doi:10.1016/j.reprotox.2011.03.001

Cited by 30 publications

(41 citation statements)

References 51 publications

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“…Increases in epithelial branching and focal branching defects were observed at puberty (PND35) in the V-exposed group. We also reported that mammary glands from rats exposed to GV or G displayed higher levels of epithelial branching and proliferation, larger TEBs, and ductal hyperplasia than untreated rats (El Sheikh Saad et al 2011). In animals with an established estrus cycle (PND50), exposure to GV and to a lesser extent V induces the formation of abnormal hyperplasic alveolar structures.…”

Section: Introductionmentioning

confidence: 66%

“…G with a purity of 99% was synthesized (LCOO, Université Bordeaux 1, Talence, France), as previously reported (El Sheikh Saad et al 2011). V was extracted from the commercial Ronilan (BASF, Levallois-Perret, France) by JP Cravedi's Laboratory (INRA, Toulouse, France) and the final preparation was O95% pure, as described previously (Bursztyka et al 2008).…”

Section: Chemicalsmentioning

confidence: 99%

“…Procedures for handling and experimentation followed by ethical guidelines have been described elsewhere (El Sheikh Saad et al 2011). At arrival, the rats were allowed to acclimatize to the animal facility for 4 weeks before mating under conditions of 22 8C, 55% humidity, and a 12 h light:12 h darkness cycle.…”

Section: Animals and Treatmentmentioning

confidence: 99%

“…Gestational dietary exposure to low-dose V and G has also been shown to have antagonistic effects on rat fertility and on fetal germ cell development (Eustache et al 2009, Lehraiki et al 2011. We recently reported that exposure to V alters the peripubertal development of the female rat mammary gland (El Sheikh Saad et al 2011). Increases in epithelial branching and focal branching defects were observed at puberty (PND35) in the V-exposed group.…”

Section: Introductionmentioning

confidence: 95%

“…In animals with an established estrus cycle (PND50), exposure to GV and to a lesser extent V induces the formation of abnormal hyperplasic alveolar structures. We therefore hypothesized that V interferes with endocrine signaling during mammary gland development (El Sheikh Saad et al 2011). If this proves to be the case, it will be important to identify the role of this compound in hormonal signaling pathways during development.…”

Section: Introductionmentioning

confidence: 99%

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In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

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Section: Introductionmentioning

confidence: 66%

Section: Chemicalsmentioning

confidence: 99%

Section: Animals and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

et al. 2020

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Isoflavones are a class of flavonoids present in legumes and are called phytoestrogens because of their estrogen‐like activity. Endogenous estrogen is well known to regulate mammary gland morphogenesis during pregnancy. Each isoflavone also has different physiological activities. However, it is difficult to investigate the direct effect of each isoflavone in mammary morphogenesis in vivo because isoflavones are metabolized into different isoflavones by enteric bacteria. In this study, investigated are the direct influences of coumestrol, daidzein, and genistein on mammary structure development and future milk production ability of mammary epithelial cells (MECs) using in vitro culture models. Mouse MECs are cultured in Matrigel with basic fibroblast growth factor and epidermal growth factor to induce ductal branching and alveolar formation, respectively. Coumestrol and genistein inhibit ductal branching and alveolar formation by affecting the proliferation and migration of MECs with the induction of apoptosis. Daidzein hardly influences mammary structure development. Furthermore, pretreatment with coumestrol adversely affects the induction of milk production ability of MECs. These results suggest that each isoflavone differentially influences mammary morphogenesis and future milk production by affecting MEC behaviors. These results also suggest that the culture models are effective to study mammary epithelial morphogenesis in vitro.

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Dose‐dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: Studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation

Blei

Soukup

Schmalbach

et al. 2014

Molecular Nutrition Food Res

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Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin

Cited by 30 publications

References 51 publications

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

Dose‐dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: Studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation

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