Maternal Exposure to Thimerosal, An Organomercury, Affects Early Serotonergic Development In the Fetal Rat Brain

Background: Thimerosal is an organomercury preservative added to many child vaccines.  Developmental toxicity of thimerosal including autism has received considerable attention, but has not been concluded yet.  Previously, we reported “autism model rats” induced by thalidomide or valproic acid (VPA) based on human thalidomide embryopathy (Pediatr Res 58:232,2002; Int J Dev Neruosci 23:287,2005; Neurosci Res 66:2,2010), hypothesizing that exposure to thalidomide or VPA on rat E9 is critical to cause autistic phenotype to rats by perturbing early serotonergic development. However, whether maternal thimerosal exposure induces developmental disorders has not been proved yet. 

Objectives: Along these lines, we tested whether fetal E9 administration of thimerosal affects early development of serotonergic system.

Methods: Thimerosal (1 mgHg/kg in saline) was administrated by intramuscular injection into glutei maximi to E9 pregnant rats (day of insemination = E1), and then E15 fetus were dissected out.  Embryonic brains were cut along the dorsal midline and mounted flatly (whole mount preparation), and were fixed with 4% paraformaldehyde.  Development of serotonergic neurons was examined immunohistochemically using serotonin antibody.

Results: Dramatic increase of serotonin neurons of the lateral part of caudal cluster was observed in thimerosal group (n=7) compared to control (n=9) by 190% (Student’s t-test, p<0.01).  Basic structure of raphe groups between thimerosal and control was not generally affected.

Conclusions: These results suggest that exposure to thimerosal at E9 affects early serotonergic development.