Simultaneous Deletion of the Transcription Factors GATA4 and GATA6 Disrupts Both Ovarian and Testicular Development in Mice

Presentation Number: SAT-397
Date of Presentation: June 15th, 2013

Maria Beatriz Padua*, Shawna C Fox, Deborah A Morse and Sergei G Tevosian
University of Florida, Gainesville, FL

Abstract

The zinc finger transcription factors GATA4 and GATA6 are expressed in mouse gonads and they have been related to the development and function of ovaries and testes. The importance of GATA4 in testis differentiation has been previously reported (Manuylov et al., 2011). Similarly, the role of GATA4 in ovarian development and function has been recently elucidated. The loss of Gata4 expression produced a reduction in the number of developing follicles shortly after birth with subsequent cellular loss, formation of hemorrhagic follicles, ovarian cysts, and sterility. In contrast, the involvement of GATA6 in gonadogenesis is much less understood.  Here, we examined the roles of GATA4 and GATA6 proteins in sexual differentiation during embryogenesis and in adults by ablating simultaneously both genes in mice. Deletion of both genes resulted in striking phenotypes during gonadal development of both sexes. In the female, immunofluorescence (IF) analysis showed a marked decrease in the expression of the granulosa cell marker FOXL2, as early as embryonic day (E)15.5 in double mutant ovaries. Moreover, postnatal ovaries were considerably smaller, with very few FOXL2-positive cells when compared to controls, suggesting an early block in follicular development. Meiosis appeared to initiate normally, but clusters of germ cells never progressed to the follicular stage and were lost by postnatal day (PND) 9.  In the male mutant, testes were notably smaller, with irregular seminiferous tubules as compared to controls. Neither DMRT1 nor GATA1 expression were detected in the Sertoli cells by IF. However, the expression of Anti-Müllerian Hormone (AMH) was persistent in the Sertoli cells of double mutant testes at PND7. Moreover, ectopic expression of FOXL2 in the seminiferous tubules at PND30 suggested that male developmental program could not be maintained in the absence of GATA4 and GATA6 expression.

 

Nothing to Disclose: MBP, SCF, DAM, SGT