In utero and lactational exposure to fipronil in female rats: Pregnancy outcomes and sexual development

Abstract

Fipronil, a phenylpyrazole insecticide, is used in agriculture, veterinary medicine, and public health. Because this insecticide is considered a potential endocrine disruptor, the aim of this study was to examine the influence of perinatal exposure to fipronil on neonatal female reproductive system development. Pregnant rats were exposed (via gavage) daily to fipronil (0.03, 0.3, or 3 mg/kg) from gestational day 15 to day 7 after birth, and effects on the reproductive functions assessed on postnatal day (PND) 22. No signs of maternal toxicity were observed during daily treatment with fipronil. Perinatal exposure to the highest dose of fipronil (3 mg/kg) delayed the age of vaginal opening (VO) and first estrus without markedly affecting the anogenital distance (AGD). Further, exposure to 0.3 mg/kg fipronil produced a significantly shorter estrus cycle and reduced number of cycles during the period of evaluation. However, the other reproductive parameters analyzed, including fertility, hormone levels, sexual behavior, and histology of ovaries and uterus, displayed no marked alterations. In this experimental model, fipronil interfered with development of neonatal female reproductive system as evidenced by delay in VO and estrus cycle alterations without apparent significant effects on fertility. Further studies are needed to identify the mechanisms of action associated with the observed female reproductive system changes.

Preclinical Transplacental Transfer and Pharmacokinetics of Fipronil in Rats

“…At the same time, we put forward a different view that long-term exposure to fipronil may not lead to detection of the parent compound in the fetus, which is related to the half-life of fipronil itself (Tang et al, 2004), but in a short period of time, fipronil can still enter the fetus. Considering the developmental and reproductive toxicity of fipronil (JMPR, 1997;Udo et al, 2014;de Barros et al, 2016;de Barros et al, 2017), it still is a potential menace. In addition, the concentration distribution could be explained by the scheme of an in vivo animal model for the transplacental transfer of oseltamivir and oseltamivir carboxylic acid in our previous study (Lin et al, 2012).…”

“…For offspring development in rats, prenatal exposure to fipronil affects the reflex development including negative geotaxis reflex delayed and early loss of palmar grasp, suggesting the interference in the GABAergic system during brain maturation (Udo et al, 2014). In female rats, fipronil interferes with the development of the neonatal female reproductive system, which is evidenced by delay of vaginal opening and estrus cycle alteration (de Barros et al, 2016).…”

A rapid evidence assessment of the potential risk to the environment presented by active ingredients in the UK’s most commonly sold companion animal parasiticides

“…For terrestrial invertebrates, which may be exposed when contaminated water leaches into the ground, toxicity was tested extensively in soil worms. The most sensitive endpoint was decreased growth and hatching of cocoons in the earthworm Eisenia fetida , occurring after 14-day exposure to 0.02 mg imidacloprid/kg soil (Wang et al 2015 ). Evidence of toxicity in other phyla was largely absent or variable; the short-term no observed effect concentration (NOEC) was 263 μg/L in a coral species (Flores et al 2020 ) and 17,500 μg/L in a rotifer species (Gharaei et al 2020 ).…”

Hepato-Curative Effect of Cholecalciferol (Vitamin D) on Fipronil-Induced Liver Damage via Up-regulation of AMPK-α, and PPAR-γ Signaling Pathways in Male Rats

“…This may promote harmful events such as calcium homeostatic disruption and over-formation of free radicals (Al-Basher et al, 2020). Owing to the metabolic, genotoxic, and mutagenic FIP-induced effects in mice and humans, this insecticide has been incorporated into the list of endocrine disruptors (De Barros et al, 2016).…”