(309) Effects of Imidacloprid on Female Reproduction in Adult Mice

Abstract Authors: Jadesola I. Oladosu¹, Ramsés Santacruz-Márquez¹, Endia Fletcher¹, Adira Safar¹, Angela E. Dean¹, Mary
J. Laws¹, Audrey Fields¹, Stav Kramer¹, Jodi. A. Flaws¹

Abstract Text: Imidacloprid (IMI) belongs to a class of neuro-active insecticides called neonicotinoids.
Neonicotinoids are widely used insecticides because they broadly target chewing and sucking
insects such as aphids, beetles, and caterpillars. Neonicotinoids are also used in commercial
agricultural systems, sold for use in home gardens, and found in veterinary pharmaceuticals.
People are typically exposed to IMI through oral ingestion of fruits and vegetables treated with
the insecticide, through dermal contact during application, or through inhalation during
application. IMI is more water soluble than other insecticides, thus, it accumulates in the
environment, leading to chronic exposure in non-target species. Exposure to neonicotinoids has
not been regarded as a public health concern because of their high affinity for insect nicotinic
acetylcholine receptors (nAChRs) and comparatively low affinity for mammalian nAChRs.
However, our previous studies have shown that the ovary contains nAChRs, and the ovary itself
can convert IMI to toxic metabolites that have a higher affinity for nAChRs than IMI. Our previous
studies were conducted using an in vitro antral follicle culture system and thus, the effects of IMI
on the female reproductive system in vivo are less well known. Therefore, this study tested the
hypothesis that IMI exposure negatively impacts female reproductive outcomes, including
estrous cyclicity, serum estradiol levels, and fertility. To test this hypothesis, adult CD-1 female
mice were exposed to vehicle control (reverse osmosis water) or IMI (0.2 – 2000 μg/L) through
their drinking water for 30 days ad libitum. This range of doses was chosen to reflect
environmentally relevant exposures observed in epidemiological studies. After two weeks of
exposure, mice were vaginally lavaged daily for two weeks to assess estrous cyclicity. After the
30-day exposure period, sera were collected from mice during diestrus for measurement of
serum estradiol levels using enzyme-linked immunosorbent assays. In addition, some mice were
mated with proven breeder adult male mice to assess several fertility parameters, including the
mating index, fertility index, gestation index, pregnancy rate, percent female pups, pup mortality,
and the average live weight of pups. The data indicate that IMI exposure at 20 μg/L decreased
the amount of time spent in estrus and IMI exposure at 200 μg/L increased serum estradiol levels
compared to control. Additionally, the fertility trials indicate that IMI exposure for 30 days did
not significantly affect the mating index, fertility index, gestation index, the average live weight
of pups, percent female pups, or pup mortality. These data indicate that exposure to IMI may
affect estrous cyclicity and serum estradiol levels, but not overall fertility indices in mice.
Supported by NIH R21 ES03650, NIH T32 ES007326, and T32HD108075.