Pleiotropic effects of alpha-SNAP M105I mutation on oocyte biology: ultrastructural and cellular changes that adversely affect female fertility in mice.

Abstract

After sperm-oocyte fusion, cortical granules (CGs) located in oocyte cortex undergo exocytosis and their content is released into the perivitelline space to avoid polyspermy. Thus, cortical granule exocytosis (CGE) is a key process for fertilization success. We have demonstrated that alpha-SNAP -and its functional partner NSF- mediate fusion of CGs with the plasma membrane in mouse oocytes. Here, we examined at cellular and ultrastructural level oocytes from hyh (hydrocephalus with hop gait) mice, which present a missense mutation in the Napa gene that results in the substitution of methionine for isoleucine at position 105 (M105I) of alpha-SNAP. Mutated alpha-SNAP was mislocalized in hyh oocytes while NSF expression increased during oocyte maturation. Staining of CGs showed that 9.8% of hyh oocytes had abnormal localization of CGs and oval shape. Functional tests showed that CGE was impaired in hyh oocytes. Interestingly, in vitro fertilization assays showed a decreased fertilization rate for hyh oocytes. Furthermore, fertilized hyh oocytes presented an increased polyspermy rate compared to wild type ones. At ultrastructural level, hyh oocytes showed small mitochondria and a striking accumulation and secretion of degradative structures. Our findings demonstrate the negative effects of alpha-SNAP M105 mutation on oocyte biology and further confirm the relevance of alpha-SNAP in female fertility.

• Authors: Matilde de Paola, María Paz Miró, Marcelo Ratto, Luis Federico Bátiz, Marcela Alejandra Michaut
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 17374 (11 22 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31758001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
• Isoleucine
• Methionine

Topics

• Amino Acid Substitution (genetics)
• Animals
• Female
• Fertility (genetics)
• Fertilization (genetics)
• Homozygote
• Infertility, Female (genetics)
• Isoleucine (genetics)
• Male
• Metaphase (genetics)
• Methionine (genetics)
• Mice
• Mice, Transgenic
• Mutation, Missense
• Oocytes (cytology, physiology, ultrastructure)
• Oogenesis (genetics)
• Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins (genetics)