Chronic Dietary Exposure to a Low-Dose Mixture of Genistein and Vinclozolin Modifies the Reproductive Axis, Testis Transcriptome, and Fertility

Background: The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood.[br/] Objective: We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility.[br/] Methods: Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays.[br/] Results: The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the “neuroactive ligand-receptor interactions” family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production.[br/] Conclusions: Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose—albeit not environmental—of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors

Tran generational effects of xeno-hormones mixtures on development and behaviour in rats

International audienc

Effect of a diet supplemented with fat from pressed-cooked cheese, butter or palm oil on blood lipids, faecal fat excretion and body composition of rats

Projet AbsoFrom.International audienceThe study was designed to compare the effect of diets of equal calcium and fat content from pressed-cooked cheese, butter, palm oil or a chow diet, on blood lipids, faecal fat excretion and body composition in rats. Palm oil intake resulted in higher faecal saturated fatty acid (SFAs) excretion compared with pressed-cooked cheese or butter, showing the importance of the positional distribution of SFAs in triacylglycerol. However, compared with butter, cheese fat intake resulted in higher faecal fat excretion, confirming the importance of the dairy-matrix effect in the excretion of fat. Despite a high consumption of fat, animals of pressed-cooked cheese group did not gain weight (no differences in any groups) and did not accumulate fat compared with the control group, contrary to the situation with rats fed with the same amount of fat provided by vegetable oil and extracted from butter that gained fat mass compared with controls

Differential effects of perinatal, prepubertal or conception to adulthood exposures to a low dose mixture of genistein and vinclozolin on the genital tract and fertility of male rats and their unexposed progeny

Differential effects of perinatal, prepubertal or conception to adulthood exposures to a low dose mixture of genistein and vinclozolin on the genital tract and fertility of male rats and their unexposed progeny. Colloque PNR-PE <National endocrine disruptor research program

Modification des préférences gustatives et de la plasticité structurale des glandes salivaires par une exposition chronique au bisphenol A chez le rat male adulte

Modification des préférences gustatives et de la plasticité structurale des glandes salivaires par une exposition chronique au bisphenol A chez le rat male adulte. colloque de la SFOR

Submandibular salivary glands as an endocrine disruptor target: impact of the period of gensitein/vinclozolin exposure in the Rat

Submandibular salivary glands as an endocrine disruptor target: impact of the period of gensitein/vinclozolin exposure in the Rat. Colloque PNR-PE <National endocrine disruptor research program

Low doses in vivo studies of dietary endocrine disruptor mixtures: Sexual dimorphism relevance of biological target for a trans-generational study in a rodent model

Low doses in vivo studies of dietary endocrine disruptor mixtures: Sexual dimorphism relevance of biological target for a trans-generational study in a rodent model. 1. international toxicology of mixtures conferenc

Bisphenol A, genistein and vinclozolin: three endocrine disruptors which differentially affect the mammary gland development in rats

Bisphenol A, genistein and vinclozolin: three endocrine disruptors which differentially affect the mammary gland development in rats. 7. Copenhaguen workshop on endocrine disruptors (human environment, lifestyle, and genes in endocrine disruptors

Auger et al F2 2D4D vs AGD input file

2D to 4D digit ratio measured by semi-automatic image analysis vs relative anogenital distance (AGD) measured by a standardized method according to exposure conditions in the F2 unexposed generation sired by exposed fathers and unexposed mother