|Department Affiliations||Biochemistry and Molecular Biology , JHSPH|
|SOM Address||W3112 Bloomberg School of Public Health Building|
The goal of sexual reproduction is to combine the genomes of two individuals, passing DNA on to the next generation and creating a new, genetically distinct individual. We study fundamental cell biological processes in the sperm and egg, with research in two general areas.
(1) A crucial component of reproductive success is ensuring that cells inherit the correct amount of DNA. Our investigations in this area focus on how the egg membrane and cortical cytoskeleton regulate the fidelity of the female gamete’s handling of DNA. One project examines how the egg membrane prevents fertilization by more than one sperm. This is known as the membrane block to polyspermy, which works in conjunction with other mechanisms to prevent polyspermic fertilization. Polyspermic fertilization is thought to be the cause of at least 5% of spontaneous pregnancy losses in humans. However, very little is known about the membrane block to polyspermy in mammalian eggs, despite data dating back up 90 years that provide evidence for its existence. Our work has characterized the role of post-fertilization calcium signaling in the establishment of the membrane block (including collaborative studies with Carmen Williams [now at NIEHS] and Rafael Fissore [University of Massachusetts]), and we also have been examining the role of the egg cytoskeleton in regulating membrane receptivity to sperm. Read more about this workhere.
A second project in this area is focused on the egg cortex (i.e., the cortical region of the cell, just underlying the plasma membrane). The egg cortex plays roles in multiple critical functions, such as progression through meiosis, responses to sperm, and regulation of activation and developmental potential. In all cells, one of most fundamental functions of the cortex is the regulation of the cell’s shape and mechanical properties. With Doug Robinson in the Department of Cell Biology in the School of Medicine, we have been examining the mechanical properties of oocytes and eggs and have found that cortical tension changes dramatically as the egg progresses through meiosis and fertilization. Our work has also revealed that a protein family known as ERMs (an acronym that refers to the individual family members) play a key role in regulating cortical tension in eggs, as disruption of ERM function results in a decrease in cortical tension. Interestingly, this also leads to abnormalities during meiotic cytokinesis occurring in response to fertilization, suggesting that cortical mechanics are critical for the egg’s completion of meiosis.
(2) Fertilization is the process by which the gametes, the carriers of individual’s genetic contributions to the next generation, merge to create the zygote. This union involves a series of carefully orchestrated cellular interactions, mediated by multiple molecules on the surfaces of the sperm and egg. Our lab studies the molecular basis of gamete membrane interactions (adhesion and fusion) with studies of candidate gamete interaction molecules on both the sperm and on the egg. This work considers a broad range of molecular families know to play roles in cell-cell interactions, including integrins, tetraspanins, Immunoglobulin Superfamily (IgSF) members, and ADAMs. This research are also complements the studies of the membrane block to polyspermy noted above, as both lines of work are providing insights into the mechanisms underlying egg receptivity to sperm.
- Marcello, M.R., and Evans, J.P. (2010, in press) Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction, and proteolytic cleavage of sperm ADAMs. Mol.Human Reprod.
- Evans, J.P. (2009) Egg integrins: Back in the game of mammalian fertilization. ACS Chem. Biol. 4, 321-323.
- Vjugina, U., Zhu, X., Oh., E., Bracero, N., and Evans, J.P. (2009) Reduction of mouse egg surface integrin alpha9 subunit (ITGA9) reduces the egg’s ability to support sperm-egg binding and fusion. Biol. Reprod. 80, 833-841.
- Glazar, A.I. and Evans, J.P. (2009) IgSF8 (EWI-2) and CD9 in fertilization: Evidence of distinct functions for CD9 and a CD9-associated protein in mammalian sperm-egg interaction.Reprod. Fertil. Dev. 21, 293-303.
- Dalo, D.T., McCaffery, J.M., and Evans, J.P. (2008) Ultrastructural analysis of egg membrane abnormalities in post-ovulatory aged eggs. Int. J. Dev. Biol. 52, 535 – 544.
- Vjugina, U. and Evans, J.P. (2008) New insights into the molecular basis of mammalian sperm-egg membrane interactions. Front. Biosci. 13, 462-476.
- Wortzman-Show, G.B., Kurokawa, M., Fissore, R.A., and Evans, J.P. (2007) Calcium and sperm components in the establishment of the membrane block to polyspermy: studies of intracytoplasmic sperm injection (ICSI) and activation with sperm factor. Mol. Human Reprod. 13, 557-565.