# Neonicotinoid insecticides and female reproduction

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2024 · $411,847

## Abstract

Neonicotinoids are the most widely used insecticides in the world because they broadly target chewing and
sucking insects. Imidacloprid (IMI) is a common neonicotinoid that accounts for 30% of neonicotinoid sales
globally. IMI is used in commercial agricultural systems, sold for use in home gardens, and found in veterinary
pharmaceuticals in the form of flea and tick preventatives for companion animals. IMI is also used as crop
seed treatments and spreads throughout crops as they mature. Thus, IMI cannot be washed or peeled off
produce. As a result, humans are routinely exposed to IMI through consumption of contaminated food and
water as well as interactions with their pets. IMI kills insects by acting as a systemic neurotoxicant after
binding nicotinic acetylcholine receptors (nAChRs) in the nervous system. To date, exposure to IMI has not
been considered a public health concern because it is a weak agonist for mammalian nAChRs compared to
insect nAChRs. However, our preliminary data indicate that the ovary bioactivates IMI to desnitro-imidacloprid
(DNI). This is of concern because DNI has a higher affinity for nAChRs than IMI. Further, our preliminary
data indicate that the ovary contains nAChRs and that DNI is toxic to antral follicles. Specifically, DNI
exposure causes slow antral follicle growth, decreased estradiol production, follicle rupture, and increased
expression of the pro-apoptotic factor Bax in mouse antral follicles in vitro. Slow follicle growth, increased
Bax, follicle rupture, and low estradiol levels are of concern because they can lead to subfertility/infertility.
Although IMI exposure leads to production of DNI by ovarian follicles, DNI is an ovarian toxicant in vitro, and
ovarian toxicants often cause subfertility/infertility, we do not know if IMI exposure causes ovarian toxicity and
female subfertility/infertility in vivo. Thus, the goal of the proposed R21 studies is to expand our preliminary
data using a mouse model to test the hypothesis that IMI exposure leads to molecular changes in the ovary
to cause ovarian toxicity, leading to female subfertility/infertility. To test his hypothesis, we will: 1) determine
the extent to which IMI causes ovarian toxicity and female subfertility/infertility in vivo and 2) identify IMI-
induced changes in molecular factors in the ovary using spatial transcriptomics. Collectively, the proposed
R21 studies will determine whether IMI poses a female reproductive health hazard in mammals and should
be considered for regulation of use in adult women.

## Key facts

- **NIH application ID:** 10936899
- **Project number:** 1R21ES036520-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Jodi A. Flaws
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,847
- **Award type:** 1
- **Project period:** 2024-09-16 → 2026-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936899

## Citation

> US National Institutes of Health, RePORTER application 10936899, Neonicotinoid insecticides and female reproduction (1R21ES036520-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10936899. Licensed CC0.

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