Effect of atrazine on implantation and early pregnancy in 4 strains of rats.
Atrazine (ATR) is an herbicide that has been shown to have adverse reproductive effects including alterations in levels of pituitary hormones such as prolactin (prl) and luteinizing hormone (LH) in female LE rats when administered at doses of 200 mg/kg/day for 1 and 3 days. Because the action of prl in promotion of progesterone secretion is essential for the initiation of pregnancy in rats, this study was designed to examine the effect of exposure to ATR during early pregnancy on implantation and short-term pregnancy maintenance. Rats were divided into two groups representing periods of dosing with ATR prior to the diurnal or nocturnal surges of prl. Within each group, four groups consisting of four strains of rats [Holtzman (HLZ); Sprague Dawley (SD); Long Evans (LE); Fischer 344 (F344)] were each further subdivided into four ATR dosages. Rats were dosed by gavage with 0, 50, 100, or 200 mg/kg/day ATR on days 1-8 of pregnancy (day 0 = sperm +). All animals were necropsied on day 8 or 9 of pregnancy. The 200 mg/kg dose of ATR reduced body weight gain in all but one group. Two groups of animals dosed at 100 and 200 mg/kg/day in the nocturnal dosing period showed an increase in percent preimplantation loss, and both of these were F344 rats. HLZ rats were the only strain to show a significant level of postimplantation loss and a decrease in serum progesterone at 200 mg/kg/day both following diurnal and nocturnal dosing. Doses of 100 mg/kg/day also produced postimplantation loss following diurnal and nocturnal dosing, but progesterone levels were decreased only after nocturnal dosing. Alterations in serum LH were seen in several groups. Serum estradiol was significantly increased only in SD rats dosed at the diurnal interval with 200 mg/kg ATR. We conclude that F344 rats are most susceptible to preimplantation effects of ATR and that HLZ rats appear most sensitive to the postimplantation effects of the chemical. LE and SD rats were least sensitive to effects of ATR during very early pregnancy.
Cummings
A M
AM
Reproductive Toxicology Division, MD-72, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. cummings.audrey@epa.gov
Rhodes
B E
BE
Cooper
R L
RL
D000284:Administration, Oral; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage / Q000633:toxicity*; D002940:Circadian Rhythm; D010064:Embryo Implantation / Q000187:drug effects*; D020964:Embryo Loss / Q000139:chemically induced*; D047108:Embryonic Development / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D015430:Weight Gain / Q000187:drug effects
D006540:Herbicides; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D001280:Atrazine