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heterozygous
mice mutant for ephrin-B2 or EphB2 as reported by Yucel et al 6. Various environmental
pollutants that has antiandrogenic or estrogenic properties act as a endocrine
disrupters and they may cause the hypospadias .This may be one of the reason
of  increasing incidence of hypospadias
.These environmental pollutants includes 
insecticides utilized in agriculture, natural plant estrogens,
pharmaceuticals and coating chemicals of food cans  because they have known estrogenic activity. Rocheleau
et al 7  had done a meta-analysis of 9
studies. He had found an odds ratio for the risk of  hypospadiac offspring to be 1.2 and 1.4 for
paternal and maternal occupational exposure respectively as compared with
parents not exposed to pesticides. Increased risk of hypospadias has been
reported by Bajpai and Yadav 8  in
patients exposed to higher levels of some organochlorine pesticides. Bisphenol
A (BPA), causes the downregulation of matrix metallopeptidase 9 (MMP)
expression.It is used in plastic packings of food.So it has been implicated in
the etiology of hypospadias . During the development of genital tubercle
,5-alpha-reductase type-2 isoenzyme is present in the surrounding area of
developing urethra. This is the place from where urethral tubularization
and  midline fusion occurs.

           The endocrine disrupters pollutant having
estrogenic or anti androgenic property  inhibits the binding of testosterone and DHT
to the androgen receptors and this results in decresed size of genital tubercle
as well as decreased anogenital distance in hypospadias patients 10. 5-alpha-reductase
is responsible for development of distal urethra so inhibitors of
5-alpha-reductase  inhibit the distal
development of the urethra resulting in hypospadias. The activity of
5-alpha-reductase type 2 is inhibited by mutations of SRD5A2  gene present on chromosome 2 at band p23 which
causes masculinization defects of varying degrees11 – 13. Such patients  may present with ambiguous genitalia  or isolated hypospadias along with other
malformation such as micropenis and congenital adrenal hyperplasia. Previously
increased hypospadias incidence was reported  to maternal intake of loratidine, recent
studies have refuted this hypothesis14-16. No association of the hypospadias
and diet was found by Carmichael et al 17.  Longer CAG alleles has been reported in
isolated 

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