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EFFECTS OF 3 WEEK EXPOSURES ON REPRODUCTIVE FUNCTION IN THE FEMALE RAT TO METAM SODIUM
Citation:
MURR, A. E., R. L. COOPER, AND J. M. GOLDMAN. EFFECTS OF 3 WEEK EXPOSURES ON REPRODUCTIVE FUNCTION IN THE FEMALE RAT TO METAM SODIUM. Presented at Triangle Consortium for Reproductive Biology, Chapel Hill, NC, February 11, 2006.
Description:
Metam sodium (MS) is a soil fumigant and Category III pesticide with a relatively low toxicity in mammals. But, there is some indication that it can impair rodent reproductive function. In ovariectomized, estradiol-primed rats, a single ip injection was reported to block the luteinizing hormone (LH) surge that in intact females triggers the final stages of pre-ovulatory follicular and oocytic maturation. The effect paralleled a fall in hypothalamic norepinephrine (NE) that was likely due to a block in dopamine-beta-hydroxylase activity. This study was designed to explore a potential effect of MS exposures on estrous cyclicity, the LH surge & ovulation. Normally cycling 90d S-D rats were administered MS (0,50,100 or 200 mg/kg/d, oral gavage) for 3 weeks and cyclicity monitored daily over this period. In animals cycling normally during the 3rd week, a small amount of proestrous blood was sampled for LH at 1430, 1600, 1730, 1900 and 2030 hrs. On the day of estrus between 21 & 26 days of dosing, cycling animals were euthanized for oocyte retrieval. The hypothalamus, along with caudate (CAU) tissue, was dissected out and analyzed by HPLC for catecholamine concentrations. Results showed that shortly after the beginning of exposure there occurred a dose-related period of extended diestrus (possibly reflecting a pseudopregnancy) that typically lasted 8-16 days. Cycling was then reinstated, and no effects were seen on the magnitude/timing of the LH surge or ovulated oocyte numbers. Anterior and posterior hypothalamic NE and dopamine (DA) were not significantly different from controls, although DA turnover (as reflected by the DOPAC/DA ratio) in both anterior hypothalamic and CAU regions was decreased at all MS dosages. The data indicate that a 3 week oral exposure to MS induced an initial period of extended diestrus before the resumption of apparently normal reproductive activity, with previously reported catecholamine alterations (apart from a persistent alteration in the DOPAC/DA ratio) being normalized by the end of exposure. (This abstract does not represent USEPA policy)