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Figure 4
Mechanisms of impaired fertility in Tg mice overexpressing DYRK1A. Hypogonadotropic hypogonadism (a) might be induced by central overexpression of DYRK1A in the hypothalamus and/or the pituitary; the overexpression might be responsible for lowering the production of LH and FSH gonadotrophins. In the testis, low LH levels slow down steroidogenesis and reduce testosterone levels, which in turn reduced spermatogenesis stimulation and upregulation of AMH levels in Sertoli cells. In germ cells (b), overexpression of DYRK1A in the early stages of spermatogenesis prompts spermatogonia to self-renew rather than to differentiate and enter meiosis. This process might be mediated by activation of STAT3 and GDNF, downregulation of retinoic acid (RA), and perturbation of the mitosis-to-meiosis transition by excess AMH.