Successful human reproduction is a complex process which requires normal function of 2 individuals. Reproductive toxicants can impair reproduction by acting in the male, female or both. Reproductive toxicants can produce their adverse effects by several direct and indirect mechanisms. The mechanisms by which reproductive toxicants impair reproduction are reviewed.
1. Aitio A (1978). Conjugation Reactions in Drug Biotransformation.Elsevier, New York.
2.
2. Aronson JK and Grahame-Smith DG (1981). Clinical pharmacology, adverse drug interactions.Brit. Med. J.282: 288–291.
3.
3. Barlow SM and Sullivan FM (1983). Reproductive Hazards of Industrial Chemicals.Academic Press, New York.
4.
4. Barrette JC, Wong A, and McLachlan JA (1981). Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci.Science212: 1402–1404.
5.
5. Busta A (1979). Poland (as reported by Stadnicka). Academy of Medicine, Krakow, Doctoral Thesis.
6.
6. Carmel PW, Araki S, and Ferin M (1976). Pituitary stalk portal blood collection in rhesus monkeys: Evidence of pulsatile release of gonadotropin-releasing hormone (GnRH).Endocrinology99: 243–248.
7.
7. Casarett LJ and Doull J (1975). Toxicology. The Basic Science of Poisons.Macmillan, New York.
8.
8. Chen YT, Mattison DR, Feigenbaum L, Fukai H, and Schulman JD (1982). Reduction in oocyte number following prenatal exposure to a high galactose diet.Science214: 1145–1147.
9.
9. Chen YT, Mattison DR, Bercu BB, and Shulman JD (1984). Resistance of the male gonad to a high galactose diet.Pediatr. Res.18: 345–348.
10.
10. Der R, Fakim Z, Yousef M, and Fakim M (1977). Effects of cadmium on growth, sexual development, and metabolism in female rats.Res. Comm. Chem. Pathol. Pharmacol.16: 485–505.
11.
11. Dixon RL and Lee IP (1980). Pharmacokinetic and adaptation factors involved in testicular toxicity.Fed. Proc.39: 66–72.
12.
12. Elion GS and Hitchings GH (1975). Azathioprine. In: Anti-Neoplastic and Immunosuppressive Agents. II. Handbook of Experimental Pharmacology, New Series, Vol. 38/2, AC Sartorelli and DG Johns (eds). Springer-Verlag, New York, pp. 404–425.
13.
13. Fleischer S and Packer L (1978). Biomembranes, part C: Biological oxidations, microsomal cytochrome P-450, and other hemo-protein systems. In: Methods of Enzymology, Vol. 52, Academic Press, New York.
14.
14. Fuller GB, Faiman C, Winter JSD, Reyes FI, and Hobson WC (1982). Sex-dependent gonadotropin concentrations in infant chimpanzees and rhesus monkeys.Proc. Soc. Exp. Biol. Med.169: 494–500.
15.
15. Gelboin HV (1980). Benzo(a)pyrene metabolism activation and carcinogenesis: Role and regulation of mixed function oxidases and related enzymes.Physiol. Rev.60: 1107–1166.
16.
16. Generoso WM, Cain KT, Krishna M, and Huff S (1979). Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg.Proc. Natl. Acad. Sci. USA76: 435–437.
17.
17. Gorski RA (1971). Gonadal hormones and the perinatal development of neuroendocrine function. In: Frontiers in Neuroendocrinology, C Martini and WF Ganong (eds). Oxford University Press, New York, pp. 237–290.
18.
18. Grant LD, Kimmel CA, Martinez-Vargas CM, and West GL (1976). Assessment of developmental toxicity associated with chronic lead exposure.Environ. Health Perspect.17290: .
19.
19. Gunn SA, Gould T, and Anderson W (1961). Zinc protection against cadmium injury to rat testis.Arch. Pathol.71: 52–57.
20.
20. Harrington JM, Stein GF, Rivera RO, and de Morales AV (1978). Occupational hazards of formulating oral contraceptives–-A survey of plant employees.Arch. Environ. Health33: 12–15.
21.
21. Heinrichs WL and Juchau MR (1980). Extrahepatic drug metabolism: The gonads. In: Extrahepatic Metabolism of Drugs and Other Foreign Compounds, TE Gram (ed). SP Medical and Scientific Books, New York pp. 319–332.
22.
22. Hemminki K, Niemi M-L, Kyyronen P, Koskinen K, and Vainio H (1983). Spontaneous abortion as risk indicator in metal exposure. In: Reproductive and Developmental Toxicity of Metals, TW Clarkson, GF Nordberg, and PR Sager (eds). Plenum Press, New York, pp. 369–380.
23.
23. Jacquet P, Gerber GB, Leonard A, and Maes J (1977). Plasma hormone levels in normal and lead-treated pregnant mice.Experiencia33: 1375–1377.
24.
24. Janson PO (1975). Effects of luteinizing hormone on blood flow in the follicular rabbit ovary, as measured by radioactive microspheres.Acta Endocrinologica79: 122–133.
25.
25. Kar A, Das A, and Karkun J (1959). Ovarian changes in prepubertal rats after treatment with cadmium chloride.Acta Biol. Med. Germ.3: 372–399.
26.
26. Kaufman FR, Kogut MD, Donnel GN, and Gobelsmann U (1981). Hypergonadotropic hypogonadism in female patients with galactosemia.N. Engl. J. Med.304: 994–998.
27.
27. Kay HH and Mattison DR (1985). How radiation and chemotherapy affect gonadal function.Contemporary Ob/Gyn.26: 109–127.
28.
28. Kimbrough RD (1974). The toxicity of polychlorinated polycyclic compounds and related chemicals.Crit. Rev. Toxicol.2: 445–489.
29.
29. Knobil E (1980). The neuroendocrine control of gonadotropin secretion in the rhesus monkey.Rec. Prog. Horm. Res.36: 53–88.
30.
30. Korach KS, Metzler M, and McLachlan JA (1979). Diethylstilbesterol metabolites and analogs. New probes for the study of hormone action.J. Biol. Chem.254: 8963–8968.
31.
31. Kupfer D (1975). Effects of pesticides and related compounds on steroid metabolism and function.Crit. Rev. Toxicol.4: 83–124.
32.
32. Lach H and Srebro Z (1972). The oestrus cycle of mice during lead and mercury poisoning.Acta Biol. Crac. Ser. Zool.15: 121–191.
33.
33. Lamperti AA and Printz RH (1973). Effects of mercuric chloride on the reproductive cycle of the female hamster.Biol. Reprod.8: 373–387.
34.
34. Lamperti AA and Printz RH (1974). Localization, accumulation and toxic effects of mercuric chloride on the reproductive axis of the female hamster.Biol. Reprod.11: 180–186.
35.
35. Lamperti AA and Niewenhuis R (1976). The effects of mercury on the structure and function of the hypothalamo-pituitary axis in the hamster.Cell Tissue Res.170: 315–324.
36.
36. Lee IP and Dixon RL (1978). Factors influencing reproductive and genetic toxic effects on male gonads.Environ. Health Perspect.24: 117–127.
37.
37. Lehmann AR and Bridges BA (1977). DNA repair.Essays Biochem.13: 71–119.
38.
38. Leonard A, Gerber GB, and Jacquet P (1983). Effect of lead on reproductive capacity and development of mammals. In: Reproductive and Developmental Toxicity of Metals, TW Clarkson, GF Nordberg, and PR Sager (eds). Plenum Press, New York, pp. 357–368.
39.
39. Mattison DR (1982). The effects of smoking on reproduction from gametogenesis to implantation.Environ. Res.28: 410–433.
40.
40. Mattison DR (1979). Difference in sensitivity of rat and mouse primordial oocyte to destruction by polycyclic aromatic hydrocarbons.Chem. Biol. Interact.28: 133–137.
41.
41. Mattison DR (1980). How xenobiotic compounds can destroy oocytes.Contemp. Obstet. Gynecol.15: 157–169.
42.
42. Mattison DR (1981). Effects of biologically foreign compounds on reproduction. In: Drugs During Pregnancy: Clinical Perspectives, RW Abdul-Karim (ed). G. E. Stickley, Philadelphia, pp. 129–143.
43.
43. Mattison DR (1981). Drugs, xenobiotics and the adolescent: Implications for reproduction. In: Drug Metabolism in the Immature Human, LF Soyka and GP Redmond (eds). Raven Press, New York, pp. 129–143.
44.
44. Mattison DR (1983). Ovarian toxicity: Effects on sexual maturation, reproduction and menopause. In: Reproductive and Developmental Toxicity of Metals, TW Clarkson, GF Nordberg, and PR Sager (eds). Plenum Press, New York, pp. 41–91.
45.
45. Mattison DR and Nightingale MS (1982). 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.Ped. Pharmacol.2: 11–21.
46.
46. Mattison DR and Nightingale MS (1982). Prepubertal ovarian toxicity. In: Banbury Report II: Environmental Factors in Human Growth and Development, VR Hunt, MK Smith, and D Worth (eds). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 395–409.
47.
47. Mattison DR and Ross GT (1982). Oogenesis and ovulation. In: Methods for Assessing the Effects of Chemicals on Reproductive Dysfunctions, V Voulk and PJ Sheehan (eds). John Wiley Interscience, New York, pp. 217–247.
48.
48. Mattison DR, Chang L, Thorgeirsson SS, and Shiromizu K (1981). The effects of cyclophosphamide, azathioprine and 6-mercaptopurine on oocyte and follicle number in C57BL/6N mice.Res. Comm. Chem. Pathol. Pharmacol.31: 155–161.
49.
49. Mattison DR and Thorgeirsson SS (1978). Gonadal aryl hydrocarbon hydroxylase in rats and mice.Cancer Res.38: 1368–1373.
50.
50. Mattison DR and Thorgeirsson SS (1979). Ovarian aryl hydrocarbon hydroxylase activity and primordial oocyte toxicity of polycyclic aromatic hydrocarbon in mice.Cancer Res.39: 3471–3475.
51.
51. Mattison DR, West DM, and Menard RA (1979). Differences in benzo(a)pyrene metabolic profile in rat and mouse ovary.Biochem. Pharmacol.28: 2101–2104.
52.
52. Mattison DR and Thomford PJ (1987). Selection of animals for reproductive toxicology studies: An evaluation of selected assumptions in reproductive toxicity testing and risk assessment. In: Human Risk Assessment–-The Role of Animal Selections and Extrapolation, VM Rolff, AGE Wilson, WE Ribelin, WP Ridley and FA Rucker, (eds). Taylor and Francis, New York, pp. 195–213.
53.
53. Mattison DR and Jelovsek FR (1987). The role of pharmacokinetics and expert systems for risk assessment in reproductive and developmental toxicology.Environ. Health Perspect.76: 107–119.
54.
54. Mattison DR, Shiromizu K, Pendergrass JA, and Thorgeirsson SS (1983). Ontogeny of ovarian glutathione and sensitivity to primordial oocyte destruction by cyclophosphamide.Pediatr. Pharmacol.3: 49–55.
55.
55. Metzler M (1976). Metabolic activation of carcinogenic diethylstilbesterol in rodents and humans.J. Toxicol. Environ. Health (Suppl) 1: 21–35.
56.
56. Metzler M and McLachlan JA (1978). Peroxidase-mediated oxidation, a possible pathway for metabolic activation of diethylstilbesterol.Biochem. Biophys. Res. Commun.85: 874–884.
57.
57. Moore CJ, McClusky GA, Fisher SM, Macleod MC, Slaga TJ, and Selkirk JK (1980). Metabolism of carcinogenic 2-hydroxybenzo(a)pyrene in rodent and human cells.Carcinogenesis1: 979–987.
58.
58. Mukhtar H, Philpot RM, and Bend JR (1978). The postnatal development of microsomal epoxide hydrase, cytosolic glutathione-S-transferase, and mitochondrial and microsomal cytochrome P-450 in adrenals and ovaries in female rats.Drug Metab. Dispos.6: 577–583.
59.
59. Odenbro A and Kihlstrom JE (1977). Frequency of pregnancy and ova implantation in triethyl-lead treated mice.Toxicol. Appl. Pharmacol.39: 359–363.
60.
60. Oesch F (1972). Mammalian epoxide hydrase: Inducible enzymes catalyzing the inactivation of carcinogenic and cytotoxic metabolic derived from aromatic and olefinic compounds.Xenobiotica3: 305–340.
61.
61. Parizek J, Ostadolova I, Benes I, and Pitha J (1968). The effect of a subcutaneous injection of cadmium salts on the ovaries of adult rats in persistent oestrus.J. Reprod. Fertil.17: 559–562.
62.
62. Paterson ARP and Tidd DM (1975). 6-Thiopurines. In: Antineoplastic and Immunosuppressive Agents. II. Handbook of Experimental Pharmacology, New Series, Vol. 38/2, AC Sartorelli and DJ Johns (eds). Springer-Verlag, New York, pp. 384–403.
63.
63. Pedersen RA and Manigia F (1978). Ultraviolet light induced unscheduled DNA synthesis by resting and growing mouse oocytes.Mutat. Res.49: 425–429.
64.
64. Peereboom-Stegeman JHJC and Jongstra-Spaapen EJ (1979). The effect of a single sublethal administration of cadmium chloride on the microcirculation in the uterus of the rat.Toxicology13: 199–213.
65.
65. Petrusz P, Weaver CM, Grant LD, Mushak P, and Kringman MR (1979). Lead poisoning and reproduction: Effects on pituitary and serum gonadotropins in neonatal rats.Environ. Res.19: 383–391.
66.
66. Rudiger HW, Haenisch F, Metzler M, Oesch F, and Glatt HR (1979). Metabolites of diethylstilbesterol induce sister chromatid exchange in cultured human fibroblasts.Nature281: 392–394.
68. Setchell BP and Sharp RM (1981). Effect of injected human chorionic gonadotropin on capillary permeability, extra-cellular fluid volume and the flow of lymph and blood in the testis of rats.J. Endocrinol.91: 245–254.
69.
69. Shepard TH (1986). Catalog of Teratogenic Agents.The Johns Hopkins University Press, Baltimore, MD.
70.
70. Sims P and Grover PL (1974). Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis.Adv. Cancer Res.20: 165–274.
71.
71. Speilberg SP and Gordon GB (1981). Glutathione synthetase-deficient lymphocytes and acetaminophen toxicity.Clin. Pharmacol. Ther.29: 51–55.
72.
72. Stadnicka A (1980). Localization of mercury in the rat ovary after oral administration of mercury chloride.Acta Histochem.67: 227–228.
73.
73. Stowe D and Goyer RA (1971). The reproductive ability and progeny of F1 lead-toxic rats.Fertil. Steril.22: 755–760.
74.
74. Styne DM and Grumbach MM (1978). Puberty in the male and female: Its physiology and disorders. In: Reproductive Endocrinology, Physiology, Pathophysiology and Clinical Management, SSC Yen and RB Jaffe (eds). W. B. Saunders, Philadelphia, pp. 189–240.
75.
75. Sunderman FW Jr, Reid MC, Shen SK, and Kevorkian CB (1983). Embryotoxicity and teratogenicity of nickel compounds. In: Reproductive and Developmental Toxicity of Metals, TW Clarkson, GF Nordberg, and PR Sager (eds). Plenum Press, New York, pp. 399–416.
76.
76. Swartz WT and Mattison DR (1988). Galactose inhibition of ovulation.Fertil. Steril.49: 522–526.
77.
77. Takizawa K, Yagi H, Jerina DM, and Mattison DR (1985). Experimental ovarian toxicity following intraovarian injection of benzo(a)pyrene or its metabolites in mice and rats. In: Target Organ Toxicity: Gonads (Reproductive and Genetic Toxicology), R Dixon (ed). Raven Press, New York, pp. 69–94.
78.
78. Thomford PJ, Jelovsek FR, and Mattison DR (1987). Effect of oocyte number and rate of atresia on the age of menopause.Reprod. Toxicol.11: 41–51.
79.
79. Vermande-Van Eck OJ and Meigs JW (1960). Changes in the ovary of the rhesus monkey after chronic lead intoxication.Fertil. Steril.11: 223–234.
80.
80. Watanabe T, Shimada T, and Endo A (1977). Mutagenic effects of cadmium on the oocyte chromosomes of mice.Jpn. J. Hyg.32: 472–481.
81.
81. Welch RM, Levin W, and Conney AH (1969). Estrogenic action of DDT and its analogs.Toxicol. Appl. Pharmacol.14: 358–367.
82.
82. Welch RM, Levin W, Kuntzman R, Jacobson M, and Conney AH (1971). Effect of halogenated hydrocarbon insecticides on the metabolism and uterotropic action of estrogens in rats and mice.Toxicol. Appl. Pharmacol.19: 234–246.
83.
83. Wide M (1980). Interference of lead with implantation in the mouse: Effect of exogenous estradiol and progesterone.Teratology21: 187–191.
84.
84. Wide M (1983). Lead and development of the early embryo. In: Reproductive and Developmental Toxicity of Metals, TW Clarkson, GF Nordberg, and PR Sager (eds). Plenum Press, New York, pp. 343–355.
85.
85. Wildt L, Marshall G, and Knobil E (1980). Experimental induction of puberty in the infantile female rhesus monkey.Science207: 1373–1375.
86.
86. Meistrich ML and Brown CC (1983). Estimation of the increased risk of human infertility from alterations in semen characteristics.Fertil. Steril.40: 220–230.
