Association between Female Reproductive Health and Mancozeb: Systematic Review of Experimental Models

Abstract

Mancozeb is a widely used fungicide approved for use in agriculture in many countries with long persistence in the environment and consequent bioaccumulation in tissues and biological fluids. Despite the large amount of studies published in recent years, the relationship between mancozeb exposure and female reproductive health is not fully elucidated. In order to summarize current evidence on mancozeb exposure and female reproductive disease, we performed a systematic review of literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to make this review. An adapted version of the National Toxicology Program's Office of Health and Assessment and Translation (OHAT) framework was used to evaluate the risk of bias. Electronic search on two databases (PubMed and Scopus) was used to find experimental studies (in vitro and in vivo) on mancozeb exposure. The database search identified 250 scientific articles, 20 of which met our inclusion criteria. Selected data were then reviewed and summarized in tables. Overall, mancozeb represents a hazard for female reproductive health, with different mechanisms of action. Undoubtedly more experimental and epidemiological studies are required to definitively validate mancozeb as reproductive toxicant.

Keywords: female reproduction; fertility; mancozeb; systematic review.

Figure 1

Flow chart of the experimental study selection process.

Figure 2

Representative transmission electron microscopy micrograph of mancozeb subcellular damage on ovarian mouse granulosa cells. Different stages of apoptotic cell death induced in vitro (0.01 mg/mL) are detectable: (1) Early stage: cell shrinkage, formation of blebs (b), dilatation and indentation of nuclear membrane (nm), heterochromatin (He) marginalization, vacuolization (V); (2) Intermediate stage: nuclear collapse, with the formation of apoptotic bodies and loss of plasma membrane integrity (*); (3) Late stage: apoptotic bodies and cell debris associated to secondary necrosis. TEM scale bar: 2 mm.