Loratadine exerts estrogen-like effects and disrupts penile development in the mouse.
OBJECTIVE
Hypospadias is a developmental anomaly of the penis and urethra that can be steroid mediated. It is characterized by a urethral opening occurring below the normal location at the tip of the penis. The link between loratadine, the active ingredient in a common over-the-counter antihistamine, and hypospadias, the most common congenital abnormality, has been the subject of controversy. We examined the effect of in utero exposure to an over-the-counter loratadine syrup on urethral development, and expression of androgen and estrogen receptors.


METHODS
We orally gavaged pregnant dams with the equivalent of a daily dose of loratadine syrup, with 3 times that dose or with a corn oil gavage control from GD 12 through GD 17. Using gross and histological assessment and 3D reconstruction, we looked for urethral abnormalities in fetal GTs at E 19. We also used real-time quantitative PCR to characterize the expression levels of steroid receptor mRNA in the GT at E 19, a critical stage for completion of urethral and penile development in this species.


RESULTS
Loratadine syrup disrupted normal urethral development in the mouse, based on gross morphology and histological assessment, and also disrupted steroid receptor expression, producing an expression profile similar to that resulting from in utero exposure to ethinyl estradiol.


CONCLUSIONS
In utero exposure to over-the-counter loratadine syrup can result in hypospadias in this model, and creates changes in the steroid receptor mRNA expression profile similar to those elicited by a synthetic estrogen.
Willingham
Emily
E
Institute for the Study and Treatment of Hypospadias, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, California 94043, USA. ewillingham@casmail.ucsf.edu
Agras
Koray
K
Vilela
Marcelo
M
Baskin
Laurence S
LS
D000818:Animals; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects*; D017336:Loratadine / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010413:Penis / Q000187:drug effects* / Q000254:growth & development*
D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine