1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p’-DDE) is one of the main metabolites of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). DDT is an organochlorine pesticide that has been widely used to control pests and to prevent crop loss in the past century. Although its use was banned in most countries in the early 1970s because of its toxicity [1,2], the World Health Organization has allowed it to be used as an indoor spray to control the breeding of mosquitoes to control the spread of yellow fever, malaria, dengue and Zika viruses in some tropical countries [3,4]. As a result, people in these countries are at a high risk of exposure to p,p’-DDE. Moreover, p,p’-DDE is highly lipophilic, persists for prolonged periods in the environment, and accumulates in the food chain and tissues of living organisms. Koureas's study [5] showed that p,p’-DDE is still detectable in most human blood samples, particularly in Eastern Europe, Central America, and Eastern Asia. p,p’-DDE was also monitored in milk and other organs in the body, and the residual amount of p,p’-DDE in each organ was positively correlated with the fat content of that organ.

Several studies have suggested that p,p’-DDE affects heart development. Merrill's study [6] showed that the obesogenic effect of p,p’-DDE is a major determinant responsible for the association of p,p’-DDE with left ventricular (LV) mass, according to a cohort study. Truong [7] used mouse cardiomyocytes to show that p,p’-DDE can directly engage with RyR2 to favor open (leaky) confirmation, which in turn affects heart development. Keely [8] confirmed that maternal exposure to p,p’-DDE increased the risk of autism spectrum disorders in the fetus in a cohort study. However, whether embryo exposure to p,p’-DDE affects cardiovascular development remains unclear. Given that previous studies [9] have shown that embryonic exposure to DDT, a prototype of p,p’-DDE, and congeners of p,p’-DDE leads to abnormal cardiac development in mice and that zebrafish is an ideal model for investigating the toxicity of cardiac development, we exposed zebrafish embryos to p,p’-DDE to evaluate whether embryonic exposure to p,p’-DDE affects cardiovascular development.

Zebrafish have a short reproductive cycle and a large spawning capacity. More importantly, zebrafish embryos are characterized by in vitro fertilization, in vitro development, and transparent embryos, which facilitate the real-time observation of early embryonic development and organ formation. Several studies have confirmed that mammals and zebrafish have similar toxicity profiles [10]. Therefore, zebrafish are widely used in toxicological studies [11].

In this study, zebrafish embryos were exposed to dimethyl sulfoxide (DMSO) and a series of concentrations of p,p’-DDE to observe the effects of p,p’-DDE on the heart development of zebrafish embryos and larvae and to investigate its mechanism of action at the genetic level, providing a basis for subsequent studies and the establishment of animal models.