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Biomedical subjects

D R Mattison

Publications and source records attributed to D R Mattison.

At least 91 records · Page 5Linked to original sources
PubMed1984

The effect of intraovarian injection of benzo(a)pyrene on primordial oocyte number and ovarian aryl hydrocarbon [benzo(a)pyrene] hydroxylase activity.

The effect of intraovarian (io) injection of benzo(a)pyrene (BP) on primordial oocyte number, ovarian aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.1) activity, and hepatic AHH activity and P-450 content was investigated in C57BL/6N (B6) and DBA/2N (D2) mice. Ovaries were exteriorized through dorsolumbar incisions under ether anesthesia, and 1.0 microliters of corn oil or corn oil containing BP was injected directly into the ovary. Bilateral io injection of BP was ovotoxic in a time and dose dependent manner. Primordial oocyte destruction was maximal 8 days after injection in both B6 and D2 mice. Unilateral io injection of BP destroyed oocytes only in the treated ovary. The threshold dose for primordial oocyte destruction was similar in both strains, approximately 50 ng/ovary. However, ED50's were different; 1.1 micrograms/ovary in B6 and 8.9 micrograms/ovary in D2 mice. Intraperitoneal treatment with alpha-naphthoflavone (80 mg/kg) inhibited the oocyte destruction by io treatment with BP (10 micrograms/ovary) in both B6 and D2 mice. In B6 mice, ovarian AHH activity was induced by BP in the treated ovary after either bilateral, or unilateral io treatment. However, io BP treatment did not change ovarian AHH activity in D2 mice. Hepatic AHH activity and P-450 content was not altered by io BP treatment in either mouse strain. These results strengthen the hypothesis that the ovary has the capability of metabolizing BP to ovotoxic products.

Animals↗
PubMed1984

Resistance of the male gonad to a high galactose diet.

Rats were fed a 50% galactose diet during pregnancy and nursing, and the testes were later examined and hormone levels determined in male offspring. Exposure to galactose for various periods during pregnancy, throughout the entire gestation, or postnatally to nursing mother until pups were 5 wk of age produced no significant differences from control testicular weight, seminiferous tubular diameter, or microscopic appearance of the testis when the offspring became adult (66 or 127 d). Serum luteinizing hormone, follicle stimulating hormone, and testosterone levels were determined 127 d postnatally and no significant differences from controls were observed in any of the treatment groups. Blood galactose-1-phosphate levels in animals receiving the 50% galactose diet were comparable to levels observed in human galactosemia. The resistance of the rat testis to a high galactose diet is consistent with the infrequency of testicular insufficiency in human galactosemia, and contrasts with the prenatal female gonadal sensitivity to galactose previously demonstrated in the rat and the high frequency of ovarian failure in human galactosemia.

Animals↗
PubMed1984

Murine strain differences in ovotoxicity following intraovarian injection with benzo(a)pyrene, (+)-(7R,8S)-oxide, (-)-(7R,8R)-dihydrodiol, or (+)-(7R,8S)-diol-(9S,10R)-epoxide-2.

Murine ovarian tumors produced by polycyclic aromatic hydrocarbons like benzo(a)pyrene (BP) require small oocyte destruction. Small oocyte destruction was evaluated in C57BL/6N (B6), DBA/2N (D2), and C57BL/6J X DBA/ 2JF1 (B6D2F1) mice following intraovarian injection with BP, (+)-( 7R ,8S)-oxide, (-)-( 7R , 8R )-dihydrodiol [(-)-DHD], or (+)-( 7R ,8S)-diol-(9S, 10R )-epoxide-2 [(+)- DE2 ] at doses ranging from 0.01 to 30 micrograms/ovary. BP, (-)-DHD, and (+)- DE2 produced small oocyte destruction in a dose-dependent fashion. The (+)-( 7R ,8S)-oxide did not destroy small oocytes at the highest dose tested (10 micrograms/ovary). The rank orders of the calculated doses which resulted in the destruction of 50% of the small oocytes (ED50S) for small oocyte destruction were BP approximately equal to (-)-DHD greater than (+)- DE2 in all three groups of mice. However, the ED50S for BP and (-)-DHD differed considerably among B6, D2, B6D2F1 mice; ED50S were smallest in B6 mice and largest in D2 mice. The ED50S for oocyte destruction in B6D2F1 mice were intermediate or similar to ED50S for B6 mice, depending on the method used for calculation. In spite of large strain differences in ED50S for BP and (-)-DHD, the ED50S for (+)- DE2 were similar in B6, D2, and B6D2F1 mice. The similar ED50 for (+)- DE2 suggests that it is an ultimate ovotoxin and ovarian carcinogen and that the target molecule(s) and mechanism(s) of detoxification are similar in B6, D2, and B6D2F1 mice.

Animals↗
PubMed1984

Familial premature ovarian failure.

Premature menopause, ovarian failure younger than 40 years of age, is relatively rare but may preclude childbearing for some women who delay attempts at fertility. We present five kindreds in which a genetic association for premature ovarian failure is strongly suggested. Transmission is either autosomal or (less likely) X-linked dominant in these examples. Chromosomal abnormalities, history of diseases, and toxic chemical or viral exposures previously associated with premature ovarian failure could not be demonstrated in these women. This suggests that these kindreds all represent familial idiopathic premature ovarian failure. These data support the need for menopausal histories on both sides of the family for women seeking to postpone reproduction, as well as for patients with ovarian failure.

Adult↗
PubMed1984

Effect of cyclophosphamide on oocyte and follicle number in Sprague-Dawley rats, C57BL/6N and DBA/2N mice.

Oocyte and follicle destruction produced by cyclophosphamide was investigated in Sprague-Dawley (SD) rats, and inbred C57BL/6N (B6) and DBA/2N (D2) mice. Primordial oocytes were the most sensitive to destruction after intraperitoneal treatment with cyclophosphamide. A delayed decrease in the number of medium-sized follicles occurred between 1 and 2 weeks after treatment. No reduction in the number of large follicles was observed over the 3-week period of this experiment. Primordial oocyte destruction produced by cyclophosphamide occurred in a time-, dose-, strain-, and species-dependent fashion. The threshold for primordial oocyte/follicle destruction in B6 and D2 mice, and SD rats was less than 10, 40, and greater than 500 mg/kg, respectively. ED50S for primordial oocyte/follicle destruction were 49 and 137 mg/kg in B6 and D2 mice, respectively. The ED50 for oocyte destruction was greater than 500 mg/kg in SD rats. Primordial oocyte destruction occurred rapidly and was completed between 48 and 72 hours after treatment with cyclophosphamide in both murine strains. Oocyte destruction and premature ovarian failure is a significant side effect in women treated with alkylating agents. The rodent ovotoxicity model used in these experiments may be useful in elucidating mechanisms of ovotoxicity and evaluating treatment protocols designed to protect the ovary.

Animals↗
PubMed1983

Effects of toxic substances on female reproduction.

Successful reproduction requires a complex series of interdependent physiological, cellular and molecular events. In the female many of these interdependent events are vulnerable to interruption by xenobiotic compounds. The physiological steps in the female reproductive cycle are reviewed. Selected xenobiotics which interrupt this cycle are presented and their mechanisms and site of adverse effects are discussed. Finally, a more detailed discussion of chemically induced ovarian failure in the human and an experimental animal model system is presented.

Animals↗
PubMed1983

Development of a nonhuman primate model for fetoscopy.

Twenty-four fetoscopy procedures were performed on 22 monkeys (19 Macaca mulatta, one M. fascicularis, two Erythrocebus patas) with gestational ages ranging from 66 to 145 days. Insertion of the fetoscope without ultrasound guidance was easy in 14 and difficult in ten procedures. Amniotic fluid exchange with normal saline, to improve visualization, was successful in eight of 13 procedures. Fetal blood sampling was successful in four of nine attempts. Nine monkeys aborted within 17 days of the fetoscopy, the remaining 13 went to term or were used in other research protocols. Major complications included maternal hemorrhage into the amniotic fluid, inability to enter the amniotic cavity, and abortion. Maternal serum alpha-fetoprotein following fetoscopy was not a useful indicator of subsequent abortion.

Abortion, Spontaneous↗
PubMed1983

Oocyte destruction by polycyclic aromatic hydrocarbons.

Certain polycyclic aromatic hydrocarbons, ubiquitous environmental pollutants, destroy oocytes. Oocyte destruction by polycyclic hydrocarbons requires distribution of the parent hydrocarbon to the ovary where ovarian enzymes metabolize the compound to reactive intermediates responsible for ovotoxicity. Descriptive assays of polycyclic hydrocarbon metabolic activation such as the aryl hydrocarbon (benzo(a)pyrene) hydroxylase assay (AHH) are not good predictors of strain or species differences in sensitivity to polycyclic hydrocarbon ovotoxicity. Using benzo(a)pyrene as a probe of ovarian metabolic processing suggests that the rate of formation of metabolites along the metabolic pathway to the 7,8-dihydrodiol-9,10-epoxide may be the appropriate measure of the role of metabolic activation in strain or species differences in sensitivity to oocyte destruction. The multistep metabolic pathway involved in ovarian metabolic processing of benzo(a)pyrene may represent a useful model for exploring the roles of metabolic activation, detoxification, intrinsic sensitivity, and repair in reproductive toxicity.

Animals↗
PubMed1983

Female reproduction.

Reproduction in the female requires a complex sequence of integrated events including ovulation, gamete transport, fertilization, conceptus transport, implantation, fetal support, and finally parturition. Each of these individual reproductive events represents the sum of many systemic, local, cellular, and molecular interactions. All of these processes have varying degrees of susceptibility to interference by xenobiotic compounds. This chapter presents a brief review of some of these mechanisms of female reproductive biology.

Endometrium↗
PubMed1983

The mechanisms of action of reproductive toxins.

A general discussion of the mechanisms of action of reproductive toxins is presented. Reproductive toxicants may produce their adverse effects by one of several mechanisms. Some xenobiotics may act directly, either by virtue of chemical reactivity (eg, oocyte destruction by alkylating agents) or by structural similarity to endogenous molecules (eg, hormone antagonists). Other xenobiotics interrupt reproductive processes indirectly either by metabolic processing to a direct-acting toxicant (eg, prohormone or metabolic activation to reactive intermediate) or by altering endocrine homeostasis (eg, increased steroid clearance). Selected examples of compounds demonstrating reproductive toxicity by one or more of these mechanisms are tabulated and an extensive bibliography of reproductive toxins is attached.

Alkylating Agents↗
PubMed1983

Ontogeny of ovarian glutathione and sensitivity to primordial oocyte destruction by cyclophosphamide.

Ovarian reduced glutathione concentration (microgram/mg wet ovarian weight) develops from levels of less than 0.2 microgram/mg in newborn Osborn Mendel rats to plateau at 0.7 microgram/mg between the ages of 3-7 weeks of age, finally reaching mature levels of approximately 1.0 microgram/mg between 7-8 weeks of age. Ovarian reduced glutathione concentration matures somewhat faster in Sprague Dawley rats, reaching mature levels of 1.0 microgram/mg between 4-6 weeks of age. The development of ovarian glutathione from immature (less than 0.2 microgram/mg) to mature levels (1.0 microgram/mg) was also observed over similar developmental time spans in DBA/2N and C57BL/6N mice. The sensitivity of primordial oocytes to destruction by cyclophosphamide in C57BL/6N mice was considerably different at 4 and 6 weeks of age. The ED50 for primordial oocyte destruction at 4 weeks of age in C57BL/6N mice was 140 mg/kg while at 6 weeks of age the ED50 was 260 mg/kg. The increase in ovarian reduced glutathione with age and the increasing resistance to primordial oocyte destruction over the same time period are consistent with the hypothesis that glutathione plays a major role in the modulation of primordial oocyte destruction.

Age Factors↗
PubMed1982

Oocyte destruction by polycyclic aromatic hydrocarbons is not linked to the inducibility of ovarian aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity in (DBA/2N X C57BL/6N) F1 X DBA/2N backcross mice.

The role of the Ah locus and ovarian aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity (AHH, EC 1.14.14.1) in ovotoxicity produced by the polycyclic aromatic hydrocarbons benzo(a)pyrene (BP), 3-methylcholanthrene (3-MC), and 7,12-dimethylbenz(a)anthracene (DMBA) was explored in Ah-responsive and Ah-nonresponsive (DBA/2N X C57BL/6N) F1 X DBA/2N backcross (F1 X D2) mice. The F1 X D2 backcross mice were phenotyped by zoxazolamine muscle paralysis time and separated into responsive and nonresponsive groups. Basal ovarian AHH activity was similar in both responsive and nonresponsive phenotypes (0.2 fluorescence units/mg/30 minutes). After treatment with one of the three polycyclic hydrocarbons (100 mg/kg, IP), ovarian AHH activity was induced only in the responsive F1 X D2 phenotype (0.4 fluorescence units/mg/30 minutes), demonstrating that inducibility of ovarian AHH activity is associated with the Ahb allele. Although responsive and nonresponsive backcross mice difference in inducibility of ovarian AHH activity, no difference was observed in the rate of, or sensitivity to, primordial oocyte destruction by the three tested polycyclic hydrocarbons. At 15 days after treatment with a single injection of BP (100 mg/kg, IP), approximately 30% of the primordial oocytes were destroyed in both responsive and nonresponsive F1 X D2 mice. The time course for oocyte destruction over the 15-day observation period was similar in both phenotypes. DMBA (100 mg/kg, IP) destroyed all of the primordial oocytes between 9 and 12 days after treatment with similar time courses in both responsive and nonresponsive phenotypes. Treatment with 3-MC (100 mg/kg, IP) destroyed approximately 40% and 70% of the primordial oocytes in responsive and nonresponsive F1 X D2 mice, respectively. Although ovarian metabolism of polycyclic hydrocarbons is necessary for ovotoxicity, oocyte destruction is not linked to the Ah locus. Sensitivity to, or the time course of, ovotoxicity by polycyclic aromatic hydrocarbons most likely reflects the biological sum of the processes of metabolic activation, detoxication, and repair and cannot be simply represented by a single enzymatic assay such as ovarian AHH activity.

Animals↗
PubMed1981

Reduction in oocyte number following prenatal exposure to a diet high in galactose.

When pregnant rats were fed a 50 percent galactose diet there was a striking reduction in oocyte number in the offspring. The most prominent effects were noted after exposure to galactose during the premeiotic stages of oogenesis. Prenatal exposure to galactose or its metabolites may contribute to the premature ovarian failure characteristic of human galactosemia.

Animals↗
PubMed1981

The effects of cyclophosphamide, azathioprine, and 6-mercaptopurine on oocyte and follicle number in C57BL/6N mice.

Cyclophosphamide, azathioprine and 6-mercaptopurine were studied for oocyte and follicle toxicity in a murine ovarian toxicity assay system. Seven days after a single treatment with cyclophosphamide (100 mg/kg ip), 63% of the primordial follicles and 0% of the growing or large follicles and their oocytes were destroyed in four week old C57BL/6N mice. Treatment with azathioprine (100 mg/kg/day ip x 9 days) or 6-mercaptopurine (100 mg/kg/day ip x 9 days) suppressed weight gain and increased mortality but had no effect on the number of oocytes or follicles in these mice. These data are consistent with previous observations on the effects of cyclophosphamide, azathioprine and 6-mercaptopurine on human ovarian toxicity. This suggests that the murine ovarian toxicity assay system may be useful in evaluating xenobiotics, including drugs, for human ovarian toxicity.

Animals↗