Lack of maternal Heat Shock Factor 1 results in multiple cellular and developmental defects, including mitochondrial damage and altered redox homeostasis, and leads to reduced survival of mammalian oocytes and embryos.
Heat Shock Factor 1 (HSF1) is a transcription factor whose loss of function results in the inability of Hsf1(-/-) females to produce viable embryos, as a consequence of early developmental arrest. We previously demonstrated that maternal HSF1 is required in oocytes to regulate expression of chaperones, in particular Hsp90alpha, and is essential for the progression of meiotic maturation. In the present work, we used comparative morphological and biochemical analytic approaches to better understand how Hsf1(-/-) oocytes undergo irreversible cell death. We found that the metaphase II arrest in mature oocytes, cortical granule exocytosis and formation of pronuclei in zygotes were all impaired in Hsf1(-/-) mutants. Although oogenesis generated fully grown oocytes in follicles, intra-ovarian Hsf1(-/-) oocytes displayed ultrastructural abnormalities and contained dysfunctional mitochondria as well as elevated oxidant load. Finally, the apoptotic effector, caspase-3, was activated in most mutant oocytes and embryos, reflecting their commitment to apoptosis. In conclusion, our study shows that early post-ovulation events are particularly sensitive to oxidant insult, which abrogates the developmental competence of HSF1-depleted oocytes. They also reveal that Hsf1 knock-out mice constitute a genetic model that can be used to evaluate the importance of redox homeostasis in oocytes.
Bierkamp
Christiane
C
Université Toulouse, UPS, UMR 5547, Centre de Biologie du Développement, IFR 109, CNRS, UPS, 118 route de Narbonne (Bat 4R3), 31062 Toulouse Cedex 09, France. bierkamp@cict.fr
Luxey
Maëva
M
Metchat
Aïcha
A
Audouard
Christophe
C
Dumollard
Rémi
R
Christians
Elisabeth
E
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D000076249:Heat Shock Transcription Factors; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D053148:Caspase 3