Maternal transfer factors and offspring development defects induced by nitrite - Project summary With the increase of agriculture practices to satisfy global food demand, there has been an increase in pollution of nitrogenous compounds from agricultural run-off in water drinking sources. The acute ingestion of nitrite, a byproduct of this nitrogenous waste, can lead to several physiological disorders (i.e., methemoglobinemia, cardiac disorders, endocrine disruption, and neural damage). However, very little is known about continuous exposure to nitrites at the low concentrations found in our drinking water. Moreover, the effects of these chronic exposure to nitrite during pregnancy and embryo development are unknown. We hypothesize that pregnancy is a stage with high sensitivity to pollutants effects, in which nitrites can interfere with the transfer of steroids, immune factors, and transcripts to the embryo. Thus, dampening the proper neurological development and growth of the embryo. The overall goal of this research project is to assess the effect of chronic consumption of nitrate during the full gestational period. For that, we will use a live-bearing fish model, Xiphophorus couchianus, that allows having a high number of spawns per female (around 20 fully developed juveniles) in a short period (1 month). We will test our hypothesis in the following (2) specific research aims: Aim 1. To measure the effect of environmental nitrite in steroid and immune factor transfer from mother to embryo. Aim 2. To determine the effect of nitrite-induced loss of maternal factor transfer in embryo development and olfactory function. Under the first aim, we will (i) measure the transfer of steroids and immune factors into embryos from mothers exposed to several concentrations of nitrite and (ii) analyze the changes in maternal transcript transfer after nitrite treatment using taqSec transcriptomic analysis. Finally, in (iii) we will localize and measure the expression of these transcripts by spatial imaging techniques in slices from formalin-fixed, paraffin-embedded block of ovaries and embryos. In aim 2, we will characterize the neurological damage in juveniles from mothers exposed to nitrite by assessing olfactory function and cognitive behavior. The expected outcome of this work is to establish a pregnancy model that can be used to test toxicological processes derived from pollutant ingestion. Moreover, this work can inform about safe levels of environmental nitrate ingestion during pregnancy and designing preventive treatments to address the concerning increasing nitrate in drinking water.
