Projects per year
Abstract
PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3′-terminal 2′-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3-to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.
Original language | English |
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Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | Molecular Human Reproduction |
Volume | 27 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2021 |
Keywords
- Fertility
- Meiosis
- Oocyte
- piRNA
- RNA interference
- Spindle
Projects
- 2 Finished
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Controlling cell polarity and asymmetric cell division in space and time
Carroll, J., Flegg, M. & Plachta, N.
Australian Research Council (ARC), Monash University
1/01/16 → 31/12/18
Project: Research
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HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility
O'Bryan, M., Adelson, D. L. & Scott, H. S.
Australian Research Council (ARC), Monash University
3/01/12 → 31/12/14
Project: Research