The effects of imidacloprid exposure on the mouse ovary in vivo.

Imidacloprid (IMI) is an insect-selective synthetic nicotine derivative used in commercial agricultural systems, home gardening, and veterinary pharmaceuticals. People are exposed to IMI through consumption of contaminated food and water and through contact with companion animals. However, the effects of IMI on the female reproductive system are not well understood. Thus, we tested the hypothesis that IMI reaches the ovaries and adversely affects the female reproductive system. Adult female mice were orally exposed to vehicle control (dimethyl sulfoxide) or IMI for 30 days. Estrous cyclicity was monitored for the last 14 days of the dosing period and mice were euthanized in diestrus. Sera were collected for gonadotropin and sex steroid hormone quantification. Ovaries were collected for IMI and IMI metabolite quantification, and to assess follicle numbers and gene expression. IMI and metabolites were significantly higher in exposed mice compared to controls. Further, IMI decreased the number of healthy ovarian follicles and increased the ovarian expression of the enzymes Cyp2e1 and Cyp19a1 compared to control. IMI also increased circulating luteinizing hormone levels (LH), but did not affect circulating follicle-stimulating hormone levels or sex steroid hormone levels compared to control. IMI did not affect body weight, ovarian weight, or estrous cyclicity compared to control. Collectively, these data indicate that IMI reaches the ovaries and affects some female reproductive outcomes such as ovarian follicle numbers, LH levels, and ovarian expression of enzymes.