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NEUROENDOCRINE AND REPRODUCTIVE EFFECTS OF PESTICIDES
Stoker, T E., J M. Goldman, AND R L. Cooper. NEUROENDOCRINE AND REPRODUCTIVE EFFECTS OF PESTICIDES. British Toxicology Society, York, England, March 28, 2000.
Neuroendocrine and Reproductive Effects of Pesticides
1Stoker, TE, Goldman 2, JM and Cooper 2, RL.
1Gamete and Early Embryogenesis Biology Branch and 2 Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA
The concept of critical periods, or times during which certain key physiological events are required for normal reproductive function is well-established in reproductive biology. Perhaps the best studied critical periods are those present during gestational and pubertal development in which the specifically timed exposures to intrinsic hormones are necessary for sexual differentiation and normal growth and maturation of reproductive tissue. In addition, there are critical periods present during the estrous cycle of the adult female rat, when the apprearance of dramatic endocrine alterations is necessary for normal ovulatory events to occur. Studies in our laboratory have demonstrated that brief exposures to certain pesticides, applied during a sensitive window for the neural regulation of ovulation, will block the preovulatory surge of LH, and thus delay ovulation and alter fertility (i.e., pregnancy outcome). To date, our studies have identified two classes of pesticides that appear to affect the neural control of ovulation though different noradrenergic mechanisms (Cooper et al.,1999). The formamidines block the hypothalamic regulation of the LH surge by interfering with the alpha 2 NE receptor, while the dithiocarbamates inhibit the hypothalamic synthesis of norepinephrine.
It is also important to note that the same treatments extended over a period of several days before mating are without effect on ovulation and pregnancy outcome. This observation is important in the assessment of potential reproductive toxicants by demonstrating that a single exposure to environmental agents at appropriate times can adversely affect reproductive outcome. The development of tolerance following continued exposure to such substances also introduces the possibility that protocols using longer term exposure scenarios would likely miss the adverse effects noted after brief exposures.
In addition to the effects seen with these pesticides in the female, there appear to be fundamental sex differences in the sensitivity of the neuroendocrine control following exposure to these environmental compounds. For example, although we observed these effects in the female, similar studies in the adult male do not lead to a disruption of hypothalamic and pituitary control of the gonadal function. Finally, the difference in sensitivity between the male and female to these neuroendocrine toxicants indicates that subsequent work evaluating the female reproductive system may uncover a greater sensitivity to other CNS-active toxicants.
This abstract does not reflect EPA policy.
Cooper, R.L., Goldman, J.M. and Stoker, T.E. 1999 Tox. Indust. Health, 15, 26-36.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
REPRODUCTIVE TOXICOLOGY DIVISION
GAMETE AND EARLY EMBRYO BIOLOGY BRANCH