Complex ovarian defects lead to infertility in Etv5-/- female mice

Etv5 is a member of the Etv4 subfamily of Ets transcription factors. In female mice, Etv5 was previously shown to be expressed in the mouse ovary. In this work, we show that Etv5-/- female mice are infertile due to a complex reproductive phenotype. Defects in the ovarian tissue architecture were noted as early as 2 weeks of age in Etv5-/- mice. Adult Etv5-/- female mice show decreased ovulation and no interest in mating even after gonadotrophin treatment. Histological abnormalities were also noted in Etv5-/- ovaries. Injection of 17β-estradiol to gonadotrophin-treated Etv5-/- mice significantly increased ovulation, mating and fertilization rates. However, 2-cell embryos of Etv5-/- females show compromised development, suggesting a role for Etv5 in the developmental competence of embryos. Expression of aromatase (CYP11a1), 17α-hydroxylase/17,20 lyase/17,20 desmolase (CYP17a1), side-chain-cleaving enzyme (CYP19a1) and luteinizing hormone/choriogonadotropin receptor mRNAs was not significantly altered in Etv5-/- ovaries. Collectively, our results suggest that Etv5 is important for the developmental competence of germ cells and the regulation of responses to steroid hormones in female mice.