Exposure to di(2-ethyl-hexyl) phthalate (DEHP) in utero and during lactation causes long-term pituitary-gonadal axis disruption in male and female mouse offspring

The present study examined the effects in mice of exposure to di(2-ethyl-hexyl) phthalate (DEHP) throughout pregnancy and lactation on the development and function of the pituitary-gonadal axis in male and female offspring once they have attained adulthood. Groups of two to three dams were exposed with the diet from gestational d 0.5 until the end of lactation, at 0, 0.05, 5, and 500 mg DEHP/kg \ub7 d. The experiment was repeated three times (total: seven to 10 dams per treatment). The 500-mg dose caused complete pregnancy failure, whereas exposure to doses of 0.05 and 5 mg did not affect pregnancy and litter size. In total, about 30 male and 30 female offspring per group were analyzed. Offspring of the DEHP-treated groups, compared with controls, at sexual maturity showed: 1) lower body weight (decrease 20-25%, P < 0.001); 2) altered gonad weight (testes were 3c13% lighter and ovaries 3c40% heavier; P < 0.001); 3) poor germ cell quality (semen was 3c50% less concentrated and 20% less viable, and 3c10% fewer oocytes reached MII stage, P < 0.001); 4) significant lower expression of steroidogenesis and gonadotropin-receptor genes in the gonads; and 5) up-regulated gonadotropin subunit gene expression in the pituitary. In conclusion, our findings suggest that, in maternally exposed male and female mice, DEHP acts on multiple pathways involved in maintaining steroid homeostasis. Specifically, in utero and lactational DEHP exposure may alter estrogen synthesis in both sexes. This, in turn, induces dysregulation of pituitary-gonadal feedback and alters the reproductive performance of exposed animals

Effects of polychlorinated biphenyls in Cd-1 mice : reproductive toxicity and intergenerational transmission

Several studies indicate that in-utero and peri-natal exposure to polychlorinated biphenyls (PCBs) induces adverse reproductive effects but it remains unclear whether such effects may be transmitted to subsequent generations. We therefore investigated the association between maternal exposure to PCBs and reproductive health in male and female offspring over three generations.Mouse dams were fed 0, 1, 10, 100 \u3bcg/kg/day of a PCB mixture (101+118) during pregnancy and lactation. PCB levels were measured in the tissues of both dams and offspring.PCB concentrations at all doses investigated were greater in the offspring than in the dams (P 640.0001) confirming that the progeny were exposed as a result of maternal exposure. In F1 offspring, exposure to PCBs resulted in reductions in: i) testis weight (P 640.05) and seminiferous tubule diameter (P 640.05); ii) sperm viability (P 640.0001) and developmental capacity (P 640.05); iii) ovary weight (P 640.05); iv) oocyte developmental capacity (P 640.05), and in v) increased follicular atresia (P 640.0001).In females, adverse effects were observed only in the F1 animals. In contrast, male offspring exhibited reduced sperm viability and altered seminiferous tubule distribution up to the third generation, showing intergenerational transmission.In summary, our data indicate that exposure to PCBs at the time of gonadal sex determination perturbed, significantly, the reproductive physiology of male and female offspring in adulthood. Furthermore, male reproductive deficiencies may be observed in at least two further generations. These findings have significant implications for reproductive health and fertility of animals and humans

Di(2-ethylhexyl) Phthalate (DEHP) Impairs Female Fertility and Promotes Adipogenesis in C3H/N Mice

Background: Di(2-ethylhexyl) phthalate (DEHP) and its metabolites are known to affect lipid metabolism and adipogenesis, mainly by activation of PPARs. Exposure to DEHP has been linked with testicular impairment and male subfertility. However, the effects of DEHP on female reproductive health and metabolism remain to be studied in detail. Objectives: Analysis of dietary DEHP exposure on metabolism and fertility in female mice. Methods: In two independent approaches, female C3H/N mice were exposed via their diet to DEHP [0.05, 5, 500 mg/kg bw/day] for 8 weeks. Food intake, weight gain and litter size were recorded. After exposure, liver, visceral fat, and plasma were analyzed by qRTPCR and ELISA in F0 females (Study I) and F0 dams and their F1 offspring (Study II). Results: In Study I, F0 females had a significant increase in body weight, food intake, and visceral adipose tissue in all exposure groups compared with controls. In liver tissue, PPAR\u3b1 and PPAR\u3b3 transcripts were significantly changed in the 500mg group. In the same group, PPAR\u3b3 mRNA was significantly reduced in liver but not in fat tissue. Leptin and FABP4 mRNA were increased in adipose tissue, while adiponectin was decreased. In Study II, we detected a 100% abortion rate in F0 dams in the 500mg group. F1 offspring exposed in utero and during lactation had an increase in visceral fat tissue and body weight. Conclusion: DEHP impaired fertility in high concentrations and increased body weight and visceral fat depots in female C3H/N mice in environmentally relevant dosages. Although DEHP exposure was only in utero and during lactation, metabolic changes induced by DEHP did also occur in the offspring of diet-exposed females

Maternal exposure to a mixture of di(2-ethylhexyl) phthalate (DEHP) and polychlorinated biphenyls (PCBs) causes reproductive dysfunction in adult male mouse offspring

We investigated the effects of maternal exposure to the plasticizer di(2-ethylhexyl) phthalate (DEHP) and the organic industrial compounds polychlorinated biphenyls (PCBs), singly and combined, on the reproductive function of male mouse offspring. Mice dams were exposed throughout pregnancy and lactation to 1 mu g PCBs (101 +118)/kg/day, 50 mu g DEHP/kg/day, or the DEHP/PCB mixture in the diet. The mixture induced permanent alterations in adult F1 males' reproductive health in a way, differently from the single compounds. Depending on the endpoint, we observed: (1) synergy in altering the gross and histological morphology of the testis; (2) antagonism on the expression levels of genes involved in pituitary-gonadal cross-talk; (3) non-interactions on sperm parameters and testosterone production. This study illustrates the complex action of a DEHP/PCB mixture, leading to a unique panel of effects on the male reproductive system, indicating the need for research on the reproductive hazards of combined endocrine disruptors

Erzeugung und Erprobung von sauerstoffhaltigen Kraftstoffzusaetzen fuer die Herstellung von unverbleiten hochoktanigen Otto-Kraftstoffen

With 12 refs., 10 tabs., 19 figs.Available from TIB Hannover: FR 6594 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Erzeugung von oktanzahlsteigernden hoeheren Ethern und ihre anwendungstechnische Erprobung unter praxisnahen Bedingungen Schlussbericht

With 102 tabs., 130 figs.SIGLEAvailable from TIB Hannover: FR 6593 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Laser wave undulators and high gain X-ray free electron lasers

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal