Influence of Adenosine 3′:5′-Cyclic Monophosphate Analogues on Testicular Organization of Fetal Mouse Gonads In Vitro 1

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Abstract
Gonadal primordia, isolated from fetal mice on the 11th or 12th day of gestation, differentiated in vitro into morphologically distinct testes or ovaries after 7 days in culture. The addition of cAMP analogs into culture media prevented the differentiation of testis cords. Histologic examination indicated that the basement membranes of testis cords disintegrated after treatment with cAMP analogu, while development of germ cells and Leydig cells appeared to be unaffected. Fetal testes in culture secreted testosterone which increased following addition of dibutyryl-cAMP (Bt2-cAMP). Primordial germ cells reached prespermatogonial stage in the presence or absence of Bt2cAMP, suggesting that progressive differentiation of primordial germ cells is independent of testis cord organization. The Bt2cAMP-treated explants resumed testicular development after transplantation into a site beneath the kidney capsules of adult mice, although the inhibitory effect appeared irreversible in vitro. The testicular organization-preventing effect of cAMP analogs was mimicked by prostaglandins or forskolin, which are known to stimulate adenylate cyclase. The inhibitory effect of either cAMP analogs or prostaglandins was potentiated when added in combination with phosphodiesterase inhibitors. Evidently, increase of intracellular cAMP prevents the development of basement membrane and the assembly of cells to form testicular structures.