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Gestational and lactational exposure to gossypol alters the testis transcriptome

ABSTRACT: Reproductive capacity can be altered by challenges experienced during critical periods of development, including fetal development and early neonatal life. Gossypol is a polyphenolic compound, commonly found in seeds of cotton plants, that impairs male reproduction. In this study, we investigated whether the exposure to gossypol in utero and during lactation alters testis development and testis gene expression in sheep.

ORGANISM(S): Ovis aries

PROVIDER: GSE133811 | GEO | 2019/07/04

REPOSITORIES: GEO

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Gestational and lactational exposure to gossypol alters the testis transcriptome

Project description:Gestational and lactational exposure to gossypol alters the testis transcriptome

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Transcriptional responses underlying the hormetic and detrimental effects of gossypol on Helicoverpa armigera

Project description:Gut and rest of body tissue from fifth instar larvae which fed for three days a diet containing different doses of gossypol. Transcriptional profiling comparing gut and rest of body samples for three gossypol concentrations (0%, 0.016%-hormetic dose & 0.16%-detrimental dose). Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds otherwise known to be detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some Malvaceae plants. We investigated the developmental effect of gossypol in the cotton bollworm, Helicoverpa armigera, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses. Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three treatments, that is 0%, 0.016% and 0.16% gossypol , were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment.

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Heliothis virescens gene expression on gossypol suppelemented diet, larval gut and rest of body

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2016-02-06 | E-GEOD-77620 | biostudies-arrayexpress

Helicoverpa armigera gene expression on gossypol suppelemented diet, larval gut and rest of body

Project description:The transcriptional response of H. armigera larvae was analyzed after feeding on gossypol supplemented diet, a toxic secondary metabolite produced in cotton plants, to detect potential detoxification enzymes possibly involved in detoxification of gossypol by H. armigera. A one-color microarray-based gene expression analysis was performed with Cy3 labeled cRNA of gut and rest of the body of H. armigera larvae that fed on 0.016%, 0.16% gossypol and control diet. For each treatment and tissue four biological replicates were used.

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Gestational and lactational exposure to gossypol alters the testis transcriptome.

Project description:BACKGROUND:Reproductive capacity can be altered by challenges experienced during critical periods of development, including fetal development and early neonatal life. Gossypol is a polyphenolic compound, commonly found in cotton seeds, that impairs male reproduction. Here, we investigated whether the exposure to gossypol in utero and during lactation alters male reproductive function in sheep. From conception until 60 days postpartum, ewes were randomly assigned to a control diet or a gossypol-rich diet based on cottonseed. Lamb testicles were removed at 60 days of age and subjected to RNA-sequencing. RESULTS:Lambs derived from the maternal cottonseed diet showed significantly lower growth and lower testis weight as a proportion of the total body weight, and reduced testosterone levels. In addition, the testis transcriptome was significantly altered by the maternal cottonseed diet. Most of the altered genes are directly implicated in testis development and sperm biology, cell communication, iron ion metabolism, calcium homeostasis and signaling, among other functions. Interestingly, network analysis revealed that exposure to gossypol significantly disturbed coexpression patterns among spermatogenesis-related genes, suggesting a disruption in coregulation mechanisms. CONCLUSIONS:Our findings provide evidence that maternal exposure to gossypol alters male reproductive function in the offspring, with potential lasting or lifelong negative consequences.

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ATO and Gossypol for GSC treatment

Project description:Glioblastoma is one of the deadliest malignancies worldwide and is virtually incurable due to its highly infiltrative growth and limited sensitivity to conventional treatment by radiochemotherapy. It is hypothesized that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. These cells are characterized by an enhanced DNA repair capacity and expression of stemness marker genes, and elimination of this population might delay or even stop tumor recurrence following radiochemotherapy. The aim of this study was to analyze whether interference with the Hedgehog signaling (Hh) pathway or combined Hh/Notch blockade can efficiently target these cancer stem cells and sensitize them to chemotherapeutic drugs. Using tumor sphere lines and primary glioma cells we demonstrate that the Hh pathway inhibitor GANT61 (GANT) and the Hh/Notch inhibitor arsenic trioxide (ATO) are capable to synergistically decrease proliferation and induce cell death in combination with the natural cotton derived anticancer agent (-)-Gossypol (Gos). In contrast to GANT in combination with Gos, the ATO/Gos combination also strongly prevented sphere formation and recovery. These synergistic effects were associated with major proteomic changes indicating decreased cell movement, distortion of cell cycle and DNA repair, as well as markedly reduced stemness. Collectively, our data show that ATO and Gos, two drugs that are safe for use in humans, represent a promising targeted therapy approach for the synergistic and specific elimination of glioma stem-like cells.

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