Reduced Ability of Rat Preantral Ovarian Follicles to Metabolize 4-Vinyl-1-cyclohexene Diepoxide in Vitro

Flaws, Jodi A.; Salyers, Kevin L.; Sipes, I. G.; Hoyer, Patricia B.

doi:10.1006/taap.1994.1118

Cited by 51 publications

(33 citation statements)

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“…Additionally, there was also no change in mRNA levels for Cu/ZnSOD or SecSOD in any tissue fraction as a result of VCD dosing. Thus, (9).…”

Section: Mitochondrial Involvementmentioning

confidence: 97%

“…Because these cells are the physiologic targets of VCD, biochemical and molecular measurem ents made from tissue preparations of whole ovaries (also containing many larger structures) would obscure speci c measurem ents in those smallest ovarian com partm ents. Therefore, a technique for isolation of highly puri ed fractions of small preantral follicles has been developed using gentle dissociation with collagenase (9). Following dissociation, intact follicles are recovered and can be hand-sorted with micropipets into 2 preantral fractions: fraction 1 (25-100 m diameter), containing primordial, primary, and early growing follicles, and fraction 2 (100 -250 m diameter), containing larger grow in g, n ontarg eted p reantral follicles.…”

Section: Follicle Isolationmentioning

confidence: 99%

“…However, no studies have been reported by others as to whether those phase II metabolic enzymes are speci cally expressed in small preantral follicles. Using isolated ovarian small preantral follicles from rats, experim ents were performed to identify the direct ability of ovarian cells to metabolize (detoxify) VCD (Figure 3) (9). Following in vitro incubation, the smallest follicles (fraction 1) displayed a lower capacity to convert VCD to the tetrol than did larger preantral follicles (fraction 2).…”

Section: Ovarian Metabolismmentioning

confidence: 99%

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Ovarian Toxicity of 4-Vinylcyclohexene Diepoxide: A Mechanistic Model

Hoyer

Devine

et al. 2001

Toxicol Pathol

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Fem ale m ammals 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 prem ature ovarian failure (early menopuas e in women). Exposure of women to know n ovotoxican ts, 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 destroye d the majority of ovarian primordial follicles. Using VCD in rats as a generalized mode l 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 ovotoxicit y) 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 understand ing 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 wom en.

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“…Additionally, there was also no change in mRNA levels for Cu/ZnSOD or SecSOD in any tissue fraction as a result of VCD dosing. Thus, (9).…”

Section: Mitochondrial Involvementmentioning

confidence: 97%

Section: Follicle Isolationmentioning

confidence: 99%

Section: Ovarian Metabolismmentioning

confidence: 99%

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Ovarian Toxicity of 4-Vinylcyclohexene Diepoxide: A Mechanistic Model

Hoyer

Devine

et al. 2001

Toxicol Pathol

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“…Additionally, VCD metabolism in the liver and hepatic tissue of rodents results in the production and excretion of the inert compound from the body, potentially reducing its effects on predators and its bioaccumulation in the environment (Flaws et al, 1994;Keating et al, 2010;Rajapaksa et al, 2007a). However, VCD does have disadvantages which make it fall short of the ideal fertility control agent.…”

Section: Ovotoxic Xenobiotics As Agents For Wildlife Fertility Controlmentioning

confidence: 99%

All Your Eggs in One Basket: Mechanisms of Xenobiotic Induced Female Reproductive Senescence

Sobinoff¹,

Bernstein²,

McLaughlin³

2012

Senescence

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“…In animal studies, 4-vinylcyclohexene diepoxide (VCD) destroys oocytes contained in small preantral follicles. There is some evidence that adult rats may be less susceptible to VCD-induced ovotoxicity than immature rats (44). Depletion of oocytes has been associated with early menopause in women, raising concern about exposures to ovotoxic chemicals, especially given contemporary secular trends toward delaying childbearing.…”

Section: Peripuberty (Late Childhood) and Puberty (Adolescence)mentioning

confidence: 99%

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

LeMasters

Perreault

Hales

et al. 2000

Environ Health Perspect

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This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.

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Reduced Ability of Rat Preantral Ovarian Follicles to Metabolize 4-Vinyl-1-cyclohexene Diepoxide in Vitro

Cited by 51 publications

References 0 publications

Ovarian Toxicity of 4-Vinylcyclohexene Diepoxide: A Mechanistic Model

Ovarian Toxicity of 4-Vinylcyclohexene Diepoxide: A Mechanistic Model

All Your Eggs in One Basket: Mechanisms of Xenobiotic Induced Female Reproductive Senescence

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

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