Project description:Based on the developmental origin of health of disease hypothesis, we previously showed that prenatal 70% maternal food restriction (FR30) predisposes the offspring to development of pathologies in adulthood. In the present study, we focused on the hypothalamus gene expression profile of standard and high fat (HF)-fed FR30 adult offspring. Total RNA obtained from isolated hypothalami of control standard and high fat-fed adult offspring compared to prenatally undernourished (FR30) counterparts.
Project description:The present study aimed to examine the effect of high-fat diet prior to pregnancy on the liver of mouse offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy) (CTR and CTR-PP groups) or a high-fat chow (31.2% fat by energy) (HFD and HFD-PP groups) for 3−4 weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers continued on the same diet until pups reached 21 days of age (CTR and HFD), and others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to determine the effects of a high-fat diet during the pre-pregnancy period in HFD-PP/CTR and HFD/CTR-PP comparisons. RNA sample was taken from liver of 3-week-old mouse prenatally received high-fat diet prior to pregnancy, during pregnancy and lactation, or through prior to and during pregnancy and lactation, while control RNA was taken from control counterpart prenatally received normal diet alone. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.
Project description:In order to establish a rat embryonic stem cell transcriptome, mRNA from rESC cell line DAc8, the first male germline competent rat ESC line to be described and the first to be used to generate a knockout rat model was characterized using RNA sequencing (RNA-seq) analysis.
Project description:Maternal exposure to environmental contaminants during pregnancy poses a significant threat to a developing fetus, as these substances can easily cross the placenta and disrupt the neurodevelopment of offspring. Specifically, the hypothalamus is essential in the regulation of metabolism, notably during critical windows of development.An abnormal hormonal and inflammatory milieu during development can trigger persistent changes in the function of hypothalamic circuits, leading to long-lasting effects on the body’s energy homeostasis and metabolism. We recently demonstrated that gestational exposure to clinically relevant levels of benzene induces severe metabolic dysregulation in the offspring. Given the central role of the hypothalamus in metabolic control, we hypothesized that prenatal exposure to benzene impacts hypothalamic development, contributing to the adverse metabolic effects in the offspring. C57BL/6JB dams were exposed to benzene at 50 ppm in the inhalation chambers exclusively during pregnancy (from E0.5 to E19). Transcriptomic analysis of the exposed offspring at postnatal day 21 (P21) revealed hypothalamic changes in genes related to metabolic regulation, inflammation, and neurodevelopment exclusively in males. Moreover, the hypothalamus of prenatally benzene-exposed male offspring displayed alterations in orexigenic and anorexigenic projections, impairments in leptin signaling, and increased microgliosis. Additional exposure to benzene during lactation did not promote further microgliosis or astrogliosis in the offspring, while the high-fat diet (HFD) challenge in adulthood exacerbated glucose metabolism and hypothalamic inflammation in benzene-exposed offspring of both sexes. These findings reveal the persistent adverse effects of prenatal benzene exposure on hypothalamic circuits and neuroinflammation, predisposing the offspring to long-lasting metabolic health conditions.
Project description:A series of two color gene expression profiles obtained using Agilent 44K expression microarrays was used to examine sex-dependent and growth hormone-dependent differences in gene expression in rat liver. This series is comprised of pools of RNA prepared from untreated male and female rat liver, hypophysectomized (‘Hypox’) male and female rat liver, and from livers of Hypox male rats treated with either a single injection of growth hormone and then killed 30, 60, or 90 min later, or from livers of Hypox male rats treated with two growth hormone injections spaced 3 or 4 hr apart and killed 30 min after the second injection. The pools were paired to generate the following 6 direct microarray comparisons: 1) untreated male liver vs. untreated female liver; 2) Hypox male liver vs. untreated male liver; 3) Hypox female liver vs. untreated female liver; 4) Hypox male liver vs. Hypox female liver; 5) Hypox male liver + 1 growth hormone injection vs. Hypox male liver; and 6) Hypox male liver + 2 growth hormone injections vs. Hypox male liver. A comparison of untreated male liver and untreated female liver liver gene expression profiles showed that of the genes that showed significant expression differences in at least one of the 6 data sets, 25% were sex-specific. Moreover, sex specificity was lost for 88% of the male-specific genes and 94% of the female-specific genes following hypophysectomy. 25-31% of the sex-specific genes whose expression is altered by hypophysectomy responded to short-term growth hormone treatment in hypox male liver. 18-19% of the sex-specific genes whose expression decreased following hypophysectomy were up-regulated after either one or two growth hormone injections. Finally, growth hormone suppressed 24-36% of the sex-specific genes whose expression was up-regulated following hypophysectomy, indicating that growth hormone acts via both positive and negative regulatory mechanisms to establish and maintain the sex specificity of liver gene expression. For full details, see V. Wauthier and D.J. Waxman, Molecular Endocrinology (2008)