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Do alterations in follicular fluid proteases contribute to human infertility?

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

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.

Study funding

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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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Division of Reproductive Endocrinology & Infertility, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Lisa Marii Cookingham & Bradley J. Van Voorhis

  2. Department of Pharmacology, University of Iowa College of Medicine, 2-505 Bowen Science Building, Iowa City, IA, 52242, USA

    Mario Ascoli

Authors
  1. Lisa Marii Cookingham
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  2. Bradley J. Van Voorhis
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  3. Mario Ascoli
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Corresponding author

Correspondence to Lisa Marii Cookingham.

Additional information

Capsule

We performed a prospective, experimental study in IVF patients with unexplained infertility and advanced maternal age to determine if alterations in cathepsin L and/or ADAMTS-1 existed. We found no statistically significant difference in the gene expression, enzyme concentration, or enzymatic activity of either protease when compared to our control. Our findings do not support a role for protease alterations as a common cause of human infertility.

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Cookingham, L.M., Van Voorhis, B.J. & Ascoli, M. Do alterations in follicular fluid proteases contribute to human infertility?. J Assist Reprod Genet 32, 737–745 (2015). https://doi.org/10.1007/s10815-015-0447-9

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  • DOI: https://doi.org/10.1007/s10815-015-0447-9

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