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Patricia B. Hoyer - One of the best experts on this subject based on the ideXlab platform.
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2015Co-Authors: Ellen A. Cannady, Cheryl A. Dyer, Patricia B. Hoyer, Glenn I Sipes, Patricia J ChristianAbstract:D ow nloaded from 2Abstract: 4-Vinylcyclohexene (VCH), an occupational chemical, causes destruction of small pre-antral follicles (F1) in mice. Previous studies suggested that VCH is bioactivated via cytochromes P450 (Cyp 450) to the ovotoxic, diepoxide metabolite, VCD. Whereas hepatic Cyp 450 isoforms 2E1, 2A, and 2B can metabolize VCH, the role of ovarian metabolism is unknown. This study investigated expression of these isoforms in isolated ovarian fractions (F1, 25-100 µm; F2, 100-250 µm; F3,>250 µm; interstitial cells; Int) from B6C3F1 mice dosed daily (15 d; ip) with vehicle, VCH (7.4 mmol/kg/d) or VCD (0.57 mmol/kg/d). Ovaries were removed and either isolated into specific ovarian compartments for mRNA analysis, fixed for immunohistochemistry, or prepared for enzymatic assays. mRNA and protein for all isoforms were expressed/distributed in all ovarian fractions from vehicle-treated mice. In the targeted F1 follicles, VCH or VCD dosing increased (p<0.05) mRNA encoding Cyp 2E1 (645±14 % VCH
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Expression and activity of microsomal epoxide hydrolase in follicles isolated from mouse ovaries
2013Co-Authors: Ellen A. Cannady, Cheryl A. Dyer, Glenn I Sipes, Patricia J Christian, Patricia B. HoyerAbstract:Microsomal epoxide hydrolase (mEH) is involved in the detoxification of xenobiotics that are or can form epoxide metabolites, including the ovotoxicant, 4-Vinylcyclohexene (VCH). This industrial chemical is bioactivated by hepatic CYP450 to the diepoxide metabolite, VCD, which destroys mouse small preantral follicles (F1). Since ovarian mEH may play a role in VCD detoxification, these studies investigated the expression and activity of mEH in isolated ovarian fractions. Mice were given 1 or 15 daily doses (ip) of VCH (7.4 mmol/kg/day) or VCD (0.57 mmol/kg/day); 4 h following the final dose, ovaries were removed, distinct populations of intact follicles (F1, 25–100 �m; F2, 100–250 �m; F3,> 250 �m) and interstitial cells (Int) were isolated, and total RNA and protein were extracted. Real-time polymerase chain reaction and the substrate cis-stilbene oxide (CSO; 12.5 �M) were used to evaluate expression and specific activity of mEH, respectively
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ovarian expressed microsomal epoxide hydrolase role in detoxification of 4 vinylcyclohexene diepoxide and regulation by phosphatidylinositol 3 kinase signaling
Toxicology and Applied Pharmacology, 2012Co-Authors: Poulomi Bhattacharya, Patricia B. Hoyer, Nivedita Sen, Aileen F KeatingAbstract:4-Vinylcyclohexene diepoxide (VCD) is a metabolite of 4-Vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH.
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The follicle-deplete mouse ovary produces androgen
2010Co-Authors: Loretta P. Mayer, Cheryl A. Dyer, Patrick J. Devine, Patricia B. HoyerAbstract:The follicle-depleted postmenopausal ovary is enriched in in-terstitial cells that produce androgens. This study was designed to cause follicle depletion in mice using the industrial chemical, 4-Vinylcyclohexene diepoxide (VCD), and characterize the ster-oidogenic capacity of cells in the residual ovarian tissue. From a dose-finding study, the optimal daily concentration of VCD was determined to be 160 mg/kg. Female B6C3F1 immature mice were treated daily with vehicle control or VCD (160 mg kg21 day21, 15 days, i.p.). Ovaries were removed and processed for histological evaluation. On Day 15 following onset of treat-ment, primordial follicles were depleted and primary follicles were reduced to about 10 % of controls. On Day 46, primary follicles were depleted and secondary and antral follicles were reduced to 0.7 % and 2.6 % of control, respectively. Seventy-fiv
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doi:10.4061/2010/145170 Research Article A Longitudinal Study of the Effect of Genistein on Bone in Two Different Murine Models of Diminished Estrogen-Producing Capacity
2009Co-Authors: Susan Reinwald, Loretta P. Mayer, Patricia B. Hoyer, Charles H. Turner, Stephen Barnes, Connie M. WeaverAbstract:License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This experiment was designed to assess the capacity of dietary genistein (GEN), to attenuate bone loss in ovariectomized (OVX) and ovary-intact VCD-treated mice. Pretreatment of mice with 4-Vinylcyclohexene diepoxide (VCD) gradually and selectively destroys ovarian follicles whilst leaving ovarian androgen-producing cells largely intact. VCD induces a perimenopause-like condition prior to the onset of reproductive acyclicity. Sixteen-week-old C57BL/6J mice were randomized to five treatment groups: sham(SHM),OVX,SHM+VCD,OVX+GEN,andSHM+VCD+GEN.Invivo,bloodsamplesweredrawnforhormone and isoflavone analyses, estrous cycles were monitored, and X-ray imaging was performed to assess changes in bone parameters. Following sacrifice, ovaries were assessed histologically, bone microarchitecture was evaluated via microcomputed tomography, and bone mechanical properties were measured. Some effects of GEN were observed in OVX mice, but GEN effects were not abl
Glenn I Sipes - One of the best experts on this subject based on the ideXlab platform.
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Reprint requests:
2015Co-Authors: Ellen A. Cannady, Cheryl A. Dyer, Patricia B. Hoyer, Glenn I Sipes, Patricia J ChristianAbstract:D ow nloaded from 2Abstract: 4-Vinylcyclohexene (VCH), an occupational chemical, causes destruction of small pre-antral follicles (F1) in mice. Previous studies suggested that VCH is bioactivated via cytochromes P450 (Cyp 450) to the ovotoxic, diepoxide metabolite, VCD. Whereas hepatic Cyp 450 isoforms 2E1, 2A, and 2B can metabolize VCH, the role of ovarian metabolism is unknown. This study investigated expression of these isoforms in isolated ovarian fractions (F1, 25-100 µm; F2, 100-250 µm; F3,>250 µm; interstitial cells; Int) from B6C3F1 mice dosed daily (15 d; ip) with vehicle, VCH (7.4 mmol/kg/d) or VCD (0.57 mmol/kg/d). Ovaries were removed and either isolated into specific ovarian compartments for mRNA analysis, fixed for immunohistochemistry, or prepared for enzymatic assays. mRNA and protein for all isoforms were expressed/distributed in all ovarian fractions from vehicle-treated mice. In the targeted F1 follicles, VCH or VCD dosing increased (p<0.05) mRNA encoding Cyp 2E1 (645±14 % VCH
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Expression and activity of microsomal epoxide hydrolase in follicles isolated from mouse ovaries
2013Co-Authors: Ellen A. Cannady, Cheryl A. Dyer, Glenn I Sipes, Patricia J Christian, Patricia B. HoyerAbstract:Microsomal epoxide hydrolase (mEH) is involved in the detoxification of xenobiotics that are or can form epoxide metabolites, including the ovotoxicant, 4-Vinylcyclohexene (VCH). This industrial chemical is bioactivated by hepatic CYP450 to the diepoxide metabolite, VCD, which destroys mouse small preantral follicles (F1). Since ovarian mEH may play a role in VCD detoxification, these studies investigated the expression and activity of mEH in isolated ovarian fractions. Mice were given 1 or 15 daily doses (ip) of VCH (7.4 mmol/kg/day) or VCD (0.57 mmol/kg/day); 4 h following the final dose, ovaries were removed, distinct populations of intact follicles (F1, 25–100 �m; F2, 100–250 �m; F3,> 250 �m) and interstitial cells (Int) were isolated, and total RNA and protein were extracted. Real-time polymerase chain reaction and the substrate cis-stilbene oxide (CSO; 12.5 �M) were used to evaluate expression and specific activity of mEH, respectively
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effect of cyp2e1 gene deletion in mice on expression of microsomal epoxide hydrolase in response to vcd exposure
Toxicological Sciences, 2008Co-Authors: Aileen F Keating, Glenn I Sipes, Kathila S. Rajapaksa, Patricia B. HoyerAbstract:Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-Vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-Vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E1+/+ and −/− mice (129S1/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VCD exposure caused follicle loss (p < 0.05) in ovaries from both genotypes; however, after 15 days, this loss was greater (p < 0.05) in CYP2E1+/+ ovaries. In a time course (2–15 days), relative to control, VCD (5μM) caused an increase (p < 0.05) in mEH mRNA by 0.5-fold (day 10) and 1.84-fold (day 15) in CYP2E1−/− but not +/+ ovaries. 7,12-Dimethylbenz[a]anthracene (DMBA) also destroys ovarian follicles but, unlike VCD, is bioactivated by mEH to an ovotoxic 3,4-diol-1,2-epoxide metabolite. Incubation of ovaries in increasing concentrations of DMBA (0.5–1μM, 15 days) resulted in greater (p < 0.05) follicle loss in CYP2E1−/−, relative to +/+ ovaries. With greater mEH (CYP2E1−/−), increased follicle loss with DMBA (bioactivation) and decreased follicle loss with VCD (detoxification) support that ovarian expression of CYP2E1 and mEH may be linked.
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expression of ovarian microsomal epoxide hydrolase and glutathione s transferase during onset of vcd induced ovotoxicity in b6c3f1 mice
Toxicology and Applied Pharmacology, 2008Co-Authors: Aileen F Keating, Glenn I Sipes, Patricia B. HoyerAbstract:Abstract 4-Vinylcyclohexene diepoxide (VCD) specifically destroys small pre-antral follicles in the rodent ovary. VCD can be detoxified to an inactive tetrol by microsomal epoxide hydrolase (mEH), or by conjugation to glutathione (GSH) by glutathione S-transferase (GST). Formation of VCD-GSH adducts in the mouse ovary 4 h after VCD exposure (0.57 mmol/kg/day) has been demonstrated. Because the mouse ovary expresses both mEH and GST, expression of mEH and GST pi and mu during a time-course of VCD-induced ovotoxicity was evaluated in a neonatal mouse ovarian culture system. Ovaries from postnatal day 4 (PND4) B6C3F1 mice were incubated with VCD (15 μM) for 2, 4, 6, 8, 10, 12, or 15 days. Following incubation, ovaries were histologically evaluated, or assessed for mRNA or protein expression. VCD did not cause follicle loss (p > 0.05) on days 2, 4, or 6 of culture. At days 8, 10, 12, and 15, VCD reduced (p
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Effect of CYP2E1 Gene Deletion in Mice on Expression of Microsomal Epoxide Hydrolase in Response to VCD Exposure
2008Co-Authors: Aileen F Keating, Glenn I Sipes, Kathila S. Rajapaksa, Patricia B. HoyerAbstract:Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-Vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-Vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E11/1 and 2/2 mice (129S1/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VC
Aileen F Keating - One of the best experts on this subject based on the ideXlab platform.
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impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity
Toxicology and Applied Pharmacology, 2012Co-Authors: Poulomi Bhattacharya, Aileen F KeatingAbstract:The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-Vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants.
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ovarian expressed microsomal epoxide hydrolase role in detoxification of 4 vinylcyclohexene diepoxide and regulation by phosphatidylinositol 3 kinase signaling
Toxicology and Applied Pharmacology, 2012Co-Authors: Poulomi Bhattacharya, Patricia B. Hoyer, Nivedita Sen, Aileen F KeatingAbstract:4-Vinylcyclohexene diepoxide (VCD) is a metabolite of 4-Vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH.
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effect of cyp2e1 gene deletion in mice on expression of microsomal epoxide hydrolase in response to vcd exposure
Toxicological Sciences, 2008Co-Authors: Aileen F Keating, Glenn I Sipes, Kathila S. Rajapaksa, Patricia B. HoyerAbstract:Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-Vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-Vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E1+/+ and −/− mice (129S1/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VCD exposure caused follicle loss (p < 0.05) in ovaries from both genotypes; however, after 15 days, this loss was greater (p < 0.05) in CYP2E1+/+ ovaries. In a time course (2–15 days), relative to control, VCD (5μM) caused an increase (p < 0.05) in mEH mRNA by 0.5-fold (day 10) and 1.84-fold (day 15) in CYP2E1−/− but not +/+ ovaries. 7,12-Dimethylbenz[a]anthracene (DMBA) also destroys ovarian follicles but, unlike VCD, is bioactivated by mEH to an ovotoxic 3,4-diol-1,2-epoxide metabolite. Incubation of ovaries in increasing concentrations of DMBA (0.5–1μM, 15 days) resulted in greater (p < 0.05) follicle loss in CYP2E1−/−, relative to +/+ ovaries. With greater mEH (CYP2E1−/−), increased follicle loss with DMBA (bioactivation) and decreased follicle loss with VCD (detoxification) support that ovarian expression of CYP2E1 and mEH may be linked.
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expression of ovarian microsomal epoxide hydrolase and glutathione s transferase during onset of vcd induced ovotoxicity in b6c3f1 mice
Toxicology and Applied Pharmacology, 2008Co-Authors: Aileen F Keating, Glenn I Sipes, Patricia B. HoyerAbstract:Abstract 4-Vinylcyclohexene diepoxide (VCD) specifically destroys small pre-antral follicles in the rodent ovary. VCD can be detoxified to an inactive tetrol by microsomal epoxide hydrolase (mEH), or by conjugation to glutathione (GSH) by glutathione S-transferase (GST). Formation of VCD-GSH adducts in the mouse ovary 4 h after VCD exposure (0.57 mmol/kg/day) has been demonstrated. Because the mouse ovary expresses both mEH and GST, expression of mEH and GST pi and mu during a time-course of VCD-induced ovotoxicity was evaluated in a neonatal mouse ovarian culture system. Ovaries from postnatal day 4 (PND4) B6C3F1 mice were incubated with VCD (15 μM) for 2, 4, 6, 8, 10, 12, or 15 days. Following incubation, ovaries were histologically evaluated, or assessed for mRNA or protein expression. VCD did not cause follicle loss (p > 0.05) on days 2, 4, or 6 of culture. At days 8, 10, 12, and 15, VCD reduced (p
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Effect of CYP2E1 Gene Deletion in Mice on Expression of Microsomal Epoxide Hydrolase in Response to VCD Exposure
2008Co-Authors: Aileen F Keating, Glenn I Sipes, Kathila S. Rajapaksa, Patricia B. HoyerAbstract:Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-Vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-Vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E11/1 and 2/2 mice (129S1/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VC
Kary E Thompson - One of the best experts on this subject based on the ideXlab platform.
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differences between rats and mice in the involvement of the aryl hydrocarbon receptor in 4 vinylcyclohexene diepoxide induced ovarian follicle loss
Toxicology and Applied Pharmacology, 2005Co-Authors: Kary E Thompson, Glenn I Sipes, Shannon M Bourguet, Patricia J Christian, Jamie C Benedict, Jodi A Flaws, Patricia B. HoyerAbstract:Abstract Repeated dosing with the occupational chemical 4-Vinylcyclohexene diepoxide (VCD) selectively depletes small pre-antral follicles in the ovaries of rats and mice via apoptosis. The aryl hydrocarbon receptor (AhR) plays a role in mediating the effects of several xenobiotics. Therefore, this study was designed to investigate a potential role of the AhR in VCD-induced ovotoxicity. Female F344 rats, C57BL/6 mice, or AhR-deficient (−/−, AhRKO) mice were dosed daily (15 days) with vehicle, VCD (80 mg/kg, i.p.) and/or the AhR antagonist, alpha-naphthoflavone (ANF; 80 mg/kg, i.p.). Compared with controls, VCD caused a 60% reduction (P
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apoptosis induced in rats by 4 vinylcyclohexene diepoxide is associated with activation of the caspase cascades
Biology of Reproduction, 2001Co-Authors: Xiaoming Hu, Glenn I Sipes, Kary E Thompson, Patricia J Christian, Patricia B. HoyerAbstract:Previous studies have shown that ovotoxicity induced in rats by dosing with 4-Vinylcyclohexene diepoxide (VCD) is likely via acceleration of the normal rate of atresia (apoptosis). The present study was designed to investigate the apoptosis-related caspase cascades as a component of this phenomenon in isolated ovarian small follicles. Female F344 rats were given a single dose of VCD (80 mg/kg, i.p., on Day 1; a time when ovotoxicity has not been initiated), or dosed daily for 15 days (80 mg/kg, i.p., on Day 15; a time when significant ovotoxicity is underway). Ovaries were collected after the final dose. Small preantral follicles (25‐100 mm in diameter) were isolated, cellular fractions were prepared, and cleavage activity or protein expression levels of caspases-3, -8, and -9 were measured. Cytosolic caspase-3 activity was increased in small follicles (P , 0.01) by VCD treatment (Day 1, 2.86 6 0.23; Day 15, 3.25 6 0.64, VCD/control, n 5 3). This activation was not seen in large or antral follicles (not targeted by VCD). Procaspase-3 protein was increased (P , 0.05) by VCD treatment 212% over controls in small ovarian follicles in Day 15, but not Day 1-dosed rats. Immunofluorescence staining intensity was evaluated by confocal microscopy. Caspase-3 protein, located in the cytosolic compartment of oocytes and granulosa cells of preantral follicles in various stages of development, was selectively increased (P , 0.05) in primordial and small primary follicles from Day 15 VCD-dosed rats. Caspase-8 activity was increased in small follicles in Day 15, but not in Day 1-treated rats; whereas caspase-9 activity was increased by VCD on Day 1 in the mitochondrial fraction. Thus, these data provide evidence that accelerated atresia induced in small ovarian follicles in rats by VCD is associated with activation of a caspase-mediated cascade. apoptosis, follicle, ovary, signal transduction
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Ovarian toxicity of 4-Vinylcyclohexene diepoxide: A mechanistic model
2001Co-Authors: Patricia B. Hoyer, Glenn I Sipes, Kary E Thompson, Patrick J. Devine, Ovarian ToxicityAbstract:Female mammals are born with a nite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, is associated with early menopause. Thus, the potential risks posed by ovotoxic chemicals is of concern. Our studies have focused on the environmental chemical 4-Vinylcyclohexene (VCH), which is produced during the manufacture of rubber tires, ame retardants, insecticides, plasticizers, and antioxidants. Dosing of female rats and mice with the ovotoxic diepoxide metabolite of VCH, 4-Vinylcyclohexene diepoxide (VCD), for 30 days destroyed the majority of ovarian primordial follicles. Using VCD in rats as a generalized model for ovotoxicity, we determined that 1) repeated daily dosing is required, 2) cell death is via apoptosis, and 3) altered expression of speci c genes is involved. An integrated approach at the morphologic, biochemical, and molecular level was used to support these conclusions. Studies in isolated rat small preantral follicles (targeted for VCD-induced ovotoxicity) focused on the role of cell death genes, mitochondrion-associated events, and VCD metabolism. We also evaluated how this information relates to human risk for early menopause. These animal research results provide a better understanding of the potential risk of human exposure to environmental ovarian toxicants and greater insight as to the impact of these toxicants on reproductive health in women
Paolo P. Pescarmona - One of the best experts on this subject based on the ideXlab platform.
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New iron pyridylamino-bis(Phenolate) catalyst for converting CO2 into cyclic carbonates and cross-linked polycarbonates
ChemSusChem, 2015Co-Authors: Masoumeh Taherimehr, João Paulo Cardoso Costa Sertã, Christopher J. Whiteoak, Arjan W. Kleij, Paolo P. PescarmonaAbstract:The atom-efficient reaction of CO2 with a variety of epoxides has been efficiently achieved employing iron pyridylamino-bis(phenolate) complexes as bifunctional catalysts. The addition of a Lewis base co-catalyst allowed significant reduction in the amount of iron complex needed to achieve high epoxide conversions. The possibility of controlling the selectivity of the reaction towards either cyclic carbonate or polycarbonate was evaluated. An efficient switch in selectivity could be achieved when cyclic epoxides such as cyclohexene oxide and the seldom explored 1,2-epoxy-4-vinylcyclohexane were used as substrates. The obtained poly(vinylcyclohexene carbonate) presents pending vinyl groups, which allowed post-synthetic cross-linking by reaction with 1,3-propanedithiol. The cross-linked polycarbonate displayed a substantial increase in the glass transition temperature and chemical resistance, thus opening new opportunities for the application of these green polymers.
