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HENMT1 is involved in the maintenance of normal female fertility in the mouse
- Source :
- Molecular Human Reproduction. 27
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
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.
- Subjects :
- Transposable element
endocrine system
Embryology
Sterility
Mutant
Piwi-interacting RNA
Biology
Oogenesis
Transcriptome
Mice
03 medical and health sciences
0302 clinical medicine
Meiosis
Genetics
medicine
Animals
RNA, Small Interfering
Molecular Biology
030304 developmental biology
0303 health sciences
Gene Expression Regulation, Developmental
Obstetrics and Gynecology
Methyltransferases
Cell Biology
Oocyte
Cell biology
Fertility
medicine.anatomical_structure
Reproductive Medicine
Oocytes
Female
Infertility, Female
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 14602407 and 13609947
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Molecular Human Reproduction
- Accession number :
- edsair.doi.dedup.....1eb9db6241db3aebaccf370309094f6d