The Effect of Serine Proteases and Their Inhibitors on In Vitro Fertilization Outcomes

Spirina, Liudmila; Akbasheva, Olga; Dyakov, Denis; Kudisova, Ksenia; Romanova, Ekaterina; Sidorenkova, Kira; Petrov, Ilya; Samoilova, Iuliia; Merkulov, Evgeny; Shilova, Diana; Stakheeva, Marina

The Effect of Serine Proteases and Their Inhibitors on In Vitro Fertilization Outcomes

Authors

Liudmila Spirina ¹

Olga Akbasheva ¹

Denis Dyakov ¹

Ksenia Kudisova ¹

Ekaterina Romanova ¹

Kira Sidorenkova ²

Ilya Petrov ²

Iuliia Samoilova ³

Evgeny Merkulov ¹

Diana Shilova ¹

Marina Stakheeva ¹

¹ Department of Biochemistry and Molecular Biology, Siberian State Medical University, Tomsk, Russian Federation

² Department of Obstetrics and Gynecology, Siberian State Medical University, Tomsk, Russian Federation

³ Department of Pediatrics with a Course in Endocrinology, Siberian State Medical University, Tomsk, Russian Federation

Abstract

Background: Proteolysis imbalance can result in infertility. The purpose of the current study was to investigate the function of kininogen, neutrophil elastase, trypsin-like proteases, α1-protease inhibitor (α1-PI), and α2-macroglobulin (α2-MG) in blood, saliva, and follicular fluid as an indicator of the success of in vitro fertilization (IVF). Methods: In general, twenty-one women undergoing an IVF cycle, as well as a control group consisting of ten healthy women, were included. The proteinase activity was measured by the rate of hydrolysis of specific substrates. The proteinase inhibitor activity was determined by the intensity of trypsin inhibition. The analysis was conducted using R software (version 4.4.1). The significance level was set at p<0.05. Results: In women with infertility, blood activities of neutrophil elastase, α1-PI, and α2-MG were elevated, whereas kallikrein and prekallikrein activities were decreased, compared with controls. In follicular fluid, neutrophil elastase activity increased 3.4-fold, α1-PI 1.8-fold, and α2-MG 5.6-fold, whereas prekallikrein decreased by 85%, compared with women who had been infertile for fewer than five years (p<0.05). During pregnancy, kallikrein and α1- PI levels in follicular fluid were low, and unsuccessful IVF was associated with higher trypsin-like protease activity and an increased kallikrein/α1- PI ratio. Conclusion: High elastase- and trypsin-like proteinase activity, along with elevated α1- PI and α2- MG levels in blood was associated with IVF benefits. Salivary kininogenase and α2-MG can be early prognostic indicators for IVF outcomes.

Keywords

Follicular fluid

In vitro fertilization

Saliva

Serine proteases

α1

protease inhibitor

α2

macroglobulin

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