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Hum. Reprod. Advance Access originally published online on April 28, 2005
Human Reproduction 2005 20(6):1578-1585; doi:10.1093/humrep/deh837
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Association between sequence variations in genes encoding human zona pellucida glycoproteins and fertilization failure in IVF

M. Männikkö1, R.-M. Törmälä2, T. Tuuri3, A. Haltia4, H. Martikainen2, L. Ala-Kokko1,5, J.S. Tapanainen2 and J.T. Lakkakorpi2,6,7

1 Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, FIN-90014 Oulu, 2 Department of Obstetrics and Gynecology, University of Oulu, FIN-90014 Oulu, Family Federation of Finland, Infertility Clinics in 3 FIN-20100 Turku, 4 FIN-00101 Helsinki and 6 FIN-90220 Oulu, Finland and 5 Center for Gene Therapy and Department of Medicine, Tulane University, Health Sciences Center, New Orleans, LA 70112, USA

7 To whom correspondence should be addressed at: Family Federation of Finland, Oulu Infertility Clinic, Medipolis, Kiviharjuntie 11, FIN-90220 Oulu, Finland. Email: jouni.lakkakorpi{at}vaestoliitto.fi

BACKGROUND: The zona pellucida (ZP) has multiple roles in reproductive processes, including oocyte maturation, fertilization and implantation. We used, for the first time, a genetic approach to study whether human ZP genes possess structural alterations in women with unsuccesful IVF trials. In theory, this may result in gradual reduction of sperm–zona interaction and eventually in total fertilization failure (TFF). METHODS: Eighteen infertile women (TFFs) whose IVF did not result in any fertilized oocytes, whereas fertilization by ICSI was successful, were screened for mutations in ZP genes by means of conformation-sensitive gel electrophoresis. Twenty-three fertilizers in IVF (FIVFs) and 68 women with proven fertility (WPFs) constituted the two control groups. RESULTS: Altogether, 20 sequence variations were found in the ZP genes. Two variations in ZP3, one in the regulatory region (c. 1–87 T->G) and one in exon 6 [c. 894 G->A (p. K298)] existed more frequently in TFFs than in FIVF and WPF groups (P-values 0.027 and 0.008, respectively). CONCLUSIONS: Our study on ZP genes of infertile women revealed a high degree of sequence variations. This may reflect gradual reduction of fertility among TFFs, but the putative roles and influences of single variations can only be hypothesized.

Key words: allelic association/genetics/infertility/sequence variation/zona pellucida

M.Männikkö and R.-M.Törmälä equally contributed to this work.


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