Do alterations in follicular fluid proteases contribute to human infertility?
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Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations.
Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1.
The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age.
Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.
KeywordsOvulation Infertility Protease Cathepsin L ADAMTS-1
We would like to acknowledge the Division of Reproductive Endocrinology and Infertility and the University of Iowa’s Center for Advanced Reproductive Care for their support and assistance in sample collection. We would also like to thank Drs. Donna and Mark Santillan for their assistance in sample processing and use of materials from the University of Iowa REI Tissue bank. Finally, we would like to recognize Professor Miriam Bridget Zimmerman for her expertise in statistical analysis.
Conflict of interest
The authors declare that they have no conflict of interest.
This work was supported by funding from the Departments of Pharmacology and Obstetrics and Gynecology at the University of Iowa.
Compliance with ethical standards
The authors declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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