Endocrine Abstracts (2011) 27 P15

LIN28 in human ovary development and as a candidate gene for primary ovarian insufficiency

Ranna El-Khairi1, Rahul Parnaik1, Lin Lin1, Mehul Dattani1, Gerard Conway2 & John Achermann1

1University College London (UCL) Institute of Child Health, London, UK; 2University College London Hospitals, London, UK.

Background: The Lin28 family of proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a influences primordial germ cell development in mice, and overexpression of Lin28a in transgenic mice has recently been shown to influence body size, timing of puberty and litter size. The related protein LIN28B is associated with age at menarche and stature in several independent genome-wide association studies in humans.

Aim: We studied expression of LIN28A and LIN28B in early human ovary development and determined if variations in LIN28A are associated with primary ovarian insufficiency (POI).

Methods: Quantitative-RT-PCR and immunohistochemistry were performed in developing gonads. Sequencing of LIN28A was undertaken in 50 women with POI.

Results: Expression studies showed that LIN28A was upregulated during a critical stage of early human ovary development (6–9 weeks post-conception, wpc), whereas levels were lower in the developing testis and did not shown any variation over this time period. In contrast, LIN28B was expressed at a lower level than LIN28A, and did not show differential expression. Immunohistochemistry revealed strong expression of LIN28A in a population of peripheral germ cells in the developing human ovary at 7 wpc. We hypothesized that LIN28A could have an important role in human germ cell development and that disruption of LIN28A might lead to germ cell depletion and primary ovarian insufficiency (POI). Mutational analysis of LIN28A in a cohort of women with POI did not reveal any significant non-synonymous changes in this gene.

Conclusions: These findings support a role for LIN28A in early human germ cell development, but suggest that changes in LIN28A are not a common cause of POI.

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