Association between sequence variations in genes encoding human zona pellucida glycoproteins and fertilization failure in IVF.
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 unsuccessful 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.
Männikkö
M
M
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, FIN-90014 Oulu, Finland.
Törmälä
R-M
RM
Tuuri
T
T
Haltia
A
A
Martikainen
H
H
Ala-Kokko
L
L
Tapanainen
J S
JS
Lakkakorpi
J T
JT
D000328:Adult; D016022:Case-Control Studies; D004527:Egg Proteins / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005091:Exons; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics*; D017421:Sequence Analysis; D020554:Sperm Injections, Intracytoplasmic; D017211:Treatment Failure; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins