Dataset Information

P53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

ABSTRACT: The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.

SUBMITTER: Napoletano F

PROVIDER: S-EPMC5629030 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

Napoletano Francesco F Gibert Benjamin B Yacobi-Sharon Keren K Vincent Stéphane S Favrot Clémentine C Mehlen Patrick P Girard Victor V Teil Margaux M Chatelain Gilles G Walter Ludivine L Arama Eli E Mollereau Bertrand B

PLoS genetics 20170925 9

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical func ...[more]

PMID: 28945745

Similar Datasets

Project description:In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/-) mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; P</=0.004) in numbers in Sirt1-/- mice, whereas Sirt1 deficiency did not effect the efficiency oocyte production following superovulation of female mice. Furthermore, the proportion of mature sperm with elevated DNA damage ( approximately 7.5% of total epididymal sperm; P = 0.02) was significantly increased in adult Sirt1-/- males. Analysis of global gene expression by microarray analysis in Sirt1 deficient testis revealed dysregulated expression of 85 genes, which were enriched (P<0.05) for genes involved in spermatogenesis and protein sumoylation. To assess the function of Sirt1 deficient germ cells, we compared the efficiency of generating embryos and viable offspring in in vitro fertilization (IVF) experiments using gametes from Sirt1-/- and sibling Sirt1+/- mice. While viable animals were derived in both Sirt1-/- X wild type and Sirt1-/- X Sirt1-/- crosses, the efficiency of producing both 2-cell zygotes and viable offspring was diminished when IVF was performed with Sirt1-/- sperm and/or oocytes. Together, these data support an important role for Sirt1 in spermatogenesis, including spermatogenic stem cells, as well as germ cell function.

Dataset Information

P53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

Publications

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets