Abstract
Androgen action during fetal life is important for later correct development of male reproductive organs and their final size and normality. Androgen driven events preferably occurred in a narrow window called masculinization programing window that is between embryonal days e15.5 - e17.5 in rat and between 8 and 12 gestational week in human. Suppression of fetal testosterone and Insl3 production by fetal Leydig cells (LCs) impairs fetal testis development that is responsible for TDS in adulthood. TDS comprised serious congenital abnormalities as cryptorchidism, hypospadias, and adult reproductive disorders - low sperm count and testicular cancer. All they are risk factors for expression of each other. TDS has a distinct morphology of interstitial cells expressing Sertoli cell markers (AMH, GATA-4).A recent experimental model for induction of TDS in rat is gestational exposure (day e13-e21) to dibutyl phthalate (DBP). COUP-TFII (chicken ovalbumin upstream promoter transcription factor-II) was identified is a cellular biomarker for impaired development of Leydig cell (T production) in the testis after in utero exposure to DBP. Abnormal persistence of COUP-TFII in fetal LCs beyond e17.5 is associated with reduced intratesticular testosterone levels. Leydig cell dysfunction within the MPW is important in determining the risk and severity of down-stream TDS disorders. DBP treatment reduced the numbers of COUP-TFII positive non LCs (3β-HSD negative) at e21.5 and after birth to adulthood. These cells were suggested to be putative progenitor of adult LCs in the rat.Expression of COUP-TFII was study in adult rats depleted from adult LCs after exposure to ethane dimethane sulfonate (EDS). Adult LCs probably differentiates from COUP-TFII+ presumptive progenitor cells that are negative for 3β-HSD. Comparison of phenotypic expression of adult LC and putative progenitors involved several markers as COUP-TFII, androgen receptor, LH-receptor, SF-1, 3β-HSD, Insl3.
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