Is there a role for DAZL in human female fertility?

Abstract

The RNA binding protein deleted in azoospermia-like (Dazl) is a key determinant of germ cell maturation and entry into meiosis in rodents and other animal species. Although the complex phenotype of Dazl deficiency in both sexes, with defects at multiple stages of germ cell development and during meiosis, demonstrates its obligate significance in fertility in animal models, its involvement in human fertility is less clear. As an RNA binding protein, identification of the in vivo mRNA targets of DAZL is necessary to understand its influence. Thus far, only a small number of Dazl targets have been identified, which typically have pivotal roles in germ cell development and meiotic progression. However, it is likely that there are a number of additional germ cell and meiosis-relevant transcripts whose translation is affected in the absence of Dazl. Efforts to identify these RNA targets have mainly been focused on spermatogenesis, and restricted to mouse. In women, prophase I occurs in fetal life and it is during this period that the ovarian follicle pool is established, thus factors that have a role in determining the quality and quantity of the ovarian reserve may have significant impact on reproductive outcomes later in adult life. Here, we suggest that DAZL may be one such factor, and there is a need for greater understanding of the role of DAZL in human oogenesis and its contribution to lifelong female fertility.

Keywords: DAZL; DAZL RNA targets; female fertility; meiosis; oocyte quality.

Figure 1

DAZL (deleted in azoospermia-like) expression during formation of the ovarian reserve. DAZL is first expressed in germ cells prior to meiosis in human and mouse. While this continues in mouse until after follicle formation, in humans, DAZL is switched off briefly before being re-expressed in oocytes of primordial follicles. E, embryonic day; D, post-natal day; PGC, primordial germ cell; W, weeks gestation.