# Morphological and Molecular Alterations Induced by Lead in Embryos and Larvae of _[PERSON]_
## 1 Introduction  
Heavy metals are naturally found in the earth's crust, and some are essential in biological systems at very low concentrations fig [1]. These elements are considered toxic when their presence exceeds the vital dose, and heavy metal pollution is currently considered one of the most serious environmental issues [2, 3, 4, 5, 6]. Lead, among the most common heavy metals, is ubiquitous in the environment and can be found in traces in soils, plants, and water [7, 8], although it has no recognized physiological role in living organisms. For its physical and chemical properties, lead has known many applications, and has been used by humans since prehistoric eras. However, following the industrial revolution, intensive anthropogenic activities, including industrial and agricultural practices, resulted in an increased and uncontrolled discharge of lead in all environmental comparts. Lead is considered one of the most toxic and persistent elements and adversely affect humans and wildlife. Water, food, and air are key routes for human exposure in emergent nations, but lead poisoning also occurs in developed countries such as the United States. Given the risks posed to humans, lead is listed among priority substances of public health importance worldwide [4, 5, 9]. It is also one of the top three toxic pollutants of environmental concern [10, 11], occupying second place in the Priority List of Hazardous Substances [7, 12, 13, 14]. Once released into the environment, lead can enter aquatic habitats due to direct input, atmospheric deposition, erosion, or agricultural and industrial wastewater. Currently, lead pollution is so pervasive that globally many aquatic bodies are contaminated [15], and lead concentration in surface waters ranges from 0.05 \(\upmu\)g/L to 566.2 mg/L worldwide [9; 16; 17; 18]. In fish, lead can be absorbed from water, food, or sediment, but regardless of the route of entry into the body shows a high tendency to bioaccumulation in various fish tissues (including gills, liver, skin, and muscles), depending on environmental factors, species-specific features, concentration, and time of exposure [8; 19; 20]. From literature, it is known that in fish, embryos and larvae are the most sensitive life stages, and they can therefore serve as an early indicator of pollution even at low levels of exposure, which also applies to Pb and other heavy metals [21; 22; 23]. Nevertheless, Pb-induced alterations during development are largely overlooked, and most of the available studies have been conducted on adults. Pb was reported to induce several detrimental effects in adult fish, including neurotoxicity [8; 24; 25], alteration of liver metabolism [26; 27], oxidative stress induction [28; 29; 30], immunological and haematological dysfunctions [22; 31; 32; 33; 34] and alteration of gills and liver histology [35; 36; 37; 32; 33]. Here we used as model species zebrafish (_Danio rerio_), a well-acknowledged tool widely used in environmental and human health risk assessment, as proven by the growing number of studies using this organism in the past few decades [39]. Its small body size, short reproductive cycle, high fecundity, and overall easy maintenance and husbandry make zebrafish an ideal model for environmental studies; on the other hand, its high genetic homology with humans provide a powerful basis for human toxicity research and increases the translational value of this model [40; 41; 42]. Notably, the early stages of development offer a valuable tool for in vivo ecotoxicological studies and allow the extrapolation of results to other vertebrate species, including humans. World Health Organisation (WHO) and Food and Agriculture Organisation of the United Nations (FAO) have set high standard levels of daily Pb intake as acceptable (up to 7 \(\upmu\)g/kg body weight); however, no such guideline is given for infants and children, who are relatively more sensitive. An accurate assessment of human risk and human uptake of Pb is made difficult due to the unavailability of data.