Abstract
Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI.
Highlights
LIN28A and LIN28B are highly conserved RNA-binding proteins that block biogenesis of the microRNA, let-7, thereby promoting stem/progenitor cell proliferation and inhibiting differentiation (Viswanathan et al, 2008; Viswanathan and Daley, 2010)
LIN28A expression increases at key stages of early human ovary development
Analysis of LIN28A and LIN28B in human fetal gonads between 6 and 7 wpc showed significantly higher expression of LIN28A in the developing ovary compared to testis and to control tissue (Fig. 1A)
Summary
LIN28A and LIN28B are highly conserved RNA-binding proteins that block biogenesis of the microRNA (miRNA), let-7, thereby promoting stem/progenitor cell proliferation and inhibiting differentiation (Viswanathan et al, 2008; Viswanathan and Daley, 2010). These factors are emerging as important regulators of several endocrine systems. Lin28a ( known as Lin28) regulates primordial germ cell development in mice Deletion of this gene results in a reduced germ cell pool in mouse embryos, whereas overexpression of Lin28a results in greater germ cell number and larger first litter size (West et al, 2009; Zhu et al, 2010). The related factor, LIN28B has been implicated in growth and puberty as polymorphic variability in LIN28B is strongly associated with age at menarche and stature in several independent genome-wide association studies in humans (He et al, 2009, 2010; Ong et al, 2009; Perry et al, 2009; Sulem et al, 2009; Widen et al, 2010)
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