The Mechanisms of Action of Reproductive Toxins

Mattison, Donald R.

doi:10.1002/ajim.1983.4.1-2.65

Cited by 49 publications

(9 citation statements)

References 110 publications

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“…Previous experiments have demonstrated that PAHs, such as BP, are indirect-acting reproductive toxins (Mattison, 1983) capable of producing dominant lethal mutations (Santodonato et al, 19821, causing teratogenesis (Santodonato et al, 1982), altering fertility (Mattison et al, 1980;MacKenzie and Angevine, 1981), and destroying oocytes in mice (Mattison et al, 1983a,b). Although BP is capable of destroying resting oocytes, the mechanism and site of adverse effect of BP which are responsible for impairment of fertility have not yet been indentified.…”

Section: Discussionmentioning

confidence: 99%

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice

Swartz

Mattison

1985

Anat. Rec.

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Successful female reproductive function requires follicle growth, ovulation, and formation of the corpus luteum. Treatment of C57BL/6N mice with a single intraperitoneal injection of benzo(a)pyrene in doses ranging from 1 to 500 mg/kg produced a dose- and time-dependent decrease in the number of corpora lutea. This effect on the number of corpora lutea is most pronounced at 1 week after treatment, with a threshold of about 1 mg/kg, and an ED50 of 1.6 mg/kg. By 2 weeks after treatment partial recovery of follicle growth and ovulation occurred, as indicated by an increase in the ED50 to 20 mg/kg. Complete recovery of normal corpora lutea number occurs in mice treated with less than 100 mg/kg by 3 weeks after treatment, with little change in the ED50 noted between 3 and 4 weeks post-treatment, 78 mg/kg at both times. Mice treated with 100 or 500 mg/kg did not recover normal corpora lutea number over the course of this experiment. These data indicate that acute exposure to benzo(a)pyrene, and perhaps other polycyclic aromatic hydrocarbons, may have a transient adverse effect on follicle growth, ovulation, or formation of corpora lutea. A consequence of this effect, transient infertility, has been observed previously when exploring the effect of polycyclic aromatic hydrocarbons on murine reproduction.

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Section: Discussionmentioning

confidence: 99%

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice

Swartz

Mattison

1985

Anat. Rec.

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“…The polycyclic aromatic hydrocarbon (PAH), 7,12-dimethylbenz[a]anthracene (DMBA) is generated through burning of organic matter, thus, cigarette smoke and car exhaust fumes are sources of DMBA exposure (Gelboin, 1980). Women who are cigarette smokers typically suffer infertility and undergo earlier onset of menopause compared to non-smokers (Jick and Porter, 1977; Mattison, 1983; Harlow and Signorello, 2000). Low level exposures to DMBA in rats resulted in equal or greater amounts of follicle loss compared to single high dose exposures (Borman et al ., 2000).…”

Section: Introductionmentioning

confidence: 99%

Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

Bhattacharya

Keating

2012

Toxicology and Applied Pharmacology

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7,12-dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression.

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“…Similarly a low spraying velocity (t< [1][2][3][4][5] hectares/h) resulted in a fecundability ratio of 0-47 (95% CI 0.29-0.76) and is associated with the use of older spraying techniques and tractors without a cabin. These factors were assumed to cause high exposure, which was confirmed by exposure measurements in the field.…”

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confidence: 99%

Time to pregnancy and occupational exposure to pesticides in fruit growers in The Netherlands.

et al. 1994

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Objectives-Although pesticides are regularly used in agriculture, relatively little is known about possible adverse health effects, especially reproductive effects, due to occupational exposure. This explorative study investigates the relation between exposure of the fruit grower to pesticides and fecundability (probability of pregnancy) in a population of fruit growers. Methods-The analysis is based on self reported data and includes 91 pregnancies during [1978][1979][1980][1981][1982][1983][1984][1985][1986][1987][1988][1989][1990] of 43 couples. Cox' proportional hazards model was used to analyse time to pregnancy after correction for gravidity and consultation with a physician for fertility problems.Results and conclusions-Application of pesticides solely by the owner was associated with a long time to pregnancy, resulting in a fecundability ratio of 0X46 (95% confidence interval (95% CI) 0.28-0.77). Similarly a low spraying velocity (t< 1-5 hectares/h) resulted in a fecundability ratio of 0-47 (95% CI 0.29-0.76) and is associated with the use of older spraying techniques and tractors without a cabin. These factors were assumed to cause high exposure, which was confirmed by exposure measurements in the field. The effect of high exposure was mainly apparent if the couple had intended to become pregnant in the period from March-November (fecundability ratio 0-42, 95% CI 0-20-0.92). This is the period in which pesticides are applied. Out of the spraying season the effect of a high exposure was absent (fecundability ratio 0'82, 95% CI 0.33-2-02). In the high exposure group 28% of the pregnancies had been preceded by consulting a physician because of fertility problems, compared with 8% in the low exposure group. These findings indicate that an adverse effect of exposure to pesticides on fecundability is likely. (Occup Environ Med 1994;51:693-699)

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The Mechanisms of Action of Reproductive Toxins

Cited by 49 publications

References 110 publications

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice

Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

Time to pregnancy and occupational exposure to pesticides in fruit growers in The Netherlands.

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