Female reproductive toxicity after exposure to malathion or diazinon: a systematic review of rodent and human studies.

Abstract

Malathion and diazinon are pesticides widely used in agriculture as well as for domestic and veterinary purposes to control pests, such as scale insects, aphids, and fleas. However, these compounds may have harmful effects on the female genital system in humans and animals. This study conducted a systematic review of the scientific literature on the female reproductive effects in humans and rodents exposed to malathion or diazinon. The search was conducted from March to September 2024 and was updated in July 2025. It was carried out in the Embase, LILACS, PubMed, SciELO, Scopus, and Web of Science databases by using different combinations of the terms "diazinon", "malathion", "ovary", "uterus", "female reproduction", "humans", "rats", and "mice" accompanied by the Boolean operators AND or OR. A total of 241 articles were found when the search was conducted using rats or mice as exposed organisms. After removing the duplicates and excluding the articles that showed administration routes not applicable to humans and the studies that were unavailable in full, only seven articles were included in this systematic review. These studies were assessed in relation to the risk of bias as recommended by the SYRCLE's risk of bias tool. For the search involving human studies, 291 articles were found; however, only four articles were deemed relevant for this review after removing the duplicates and the studies that did not meet the eligibility criteria. Then, the included studies were evaluated in relation to the risk of bias as recommended by the Newcastle-Ottawa Scale. Afterwards, the extraction of the results was performed, and the outcomes were organized in tables. When possible, a meta-analysis was carried out with all the studies that assessed the same sexual steroid and gonadotrophic hormones in females. In this review, the results demonstrated that malathion and diazinon impair female reproduction in rodents by reducing ovarian hormone production, increasing oxidative stress, diminishing oocyte quality, and inducing histopathological changes in the reproductive organs. In humans, the included studies demonstrated that exposure to these pesticides is associated with a higher risk for developing endometriosis and an increased risk of ovarian, uterine, and thyroid cancers. After assessing the effects of these organophosphates on hormonal levels by meta-analysis in this review, it was shown a reduction in progesterone concentrations (reduction of 37.43%; overall effect size: Z = 2.05, p = 0.04; mean difference and confidence interval: -9.33 [-18.23, -0.43]) but there were no effects in estradiol (overall effect size: Z = 0.31, p = 0.76; mean difference and confidence interval: 2.66 [-14.21, -19.54]), testosterone (overall effect size: Z = 0.91, p = 0.36; mean difference and confidence interval: 0.08 [-0.09, 0.24]), FSH (overall effect size: Z = 0.86, p = 0.39; mean difference and confidence interval: -0.40 [-1.31, 0.51]), and LH (overall effect size: Z = 1.38, p = 0.17; mean difference and confidence interval: -0.75 [-1.82, 0.32]) levels. Additionally, the studies suggested that these pesticides interfere with hormonal production mechanisms by promoting cell apoptosis and autophagy in ovarian cells, which may compromise fertility in the long term. As a limitation of this review, there was a small number of included studies and a higher heterogeneity of these studies (I² ≥ 79%). In summary, female rodent exposure to these organophosphates was associated with hormonal dysregulation, impaired ovarian and uterine structure, and oxidative stress in reproductive tissues. In humans, this exposure was related to increased risk of endometriosis and hormonally associated cancers. When considering the negative impact observed on the female genital system of both rodents and humans, it is crucial to reconsider the use of these pesticides, as well as adopt less harmful alternatives to protect the reproductive health of non-target animals and human populations exposed to these substances.