Cyclophilin B serum levels present variations across the menstrual cycle

Abstract

Cyclophilins are a family of chaperones involved in inflammation and cell death. Cyclophilin B is released by inflammatory cells and acts through the receptor CD147, affecting matrix metalloproteases release, whilst cyclophilin D participates in hypoxia-induced apoptosis. Previous studies related hormones like estradiol or prolactin to these proteins, however, their blood concentrations across the menstrual cycle have not been determined. In this work, eleven healthy women (BMI: 21.8 kg/m²) were monitored during a single menstrual cycle, making blood extractions at follicular, periovulatory and mid-luteal phases. Hormone and cyclophilin levels were determined in each phase. Statistical differences were determined by repeated measures ANOVA and estimated marginal means tests, or by Friedman and Dunn-Bonferroni tests for parametric and non-parametric variables, respectively. Bivariate correlations were evaluated with the Spearman coefficient. Cyclophilin B concentrations presented significant differences during the menstrual cycle (p = 0.012). The highest levels of this protein were found at follicular extraction, followed by a decrease at periovulatory phase and a slight increase at mid-luteal phase. Cyclophilin D showed the same profile, although statistical significance was not reached. This immunophilin exhibited a positive correlation with luteinizing hormone at periovulatory phase (r = 0.743, p = 0.009) and with follicle stimulating hormone at mid-luteal phase (r = 0.633, p = 0.036). This is the first study describing the changes in cyclophilin B concentrations across the menstrual cycle, as well as the association of luteinizing and follicle stimulating hormones with cyclophilin D. These results suggest a role of these proteins in the cyclic inflammatory events that affect female reproductive system that should be explored.

Figure 1

Serum hormone concentrations across the menstrual cycle. Box-and-whisker plots of (a) luteinizing hormone (LH), (b) follicle stimulating hormone (FSH), (c) estradiol and (d) progesterone levels, measured in follicular, periovulatory and mid-luteal phases (n = 11). Statistical differences were determined by Friedman test followed by Dunn-Bonferroni test.*p < 0.05, **p < 0.01.

Figure 2

Concentration of cyclophilins B and D throughout the menstrual cycle. (a) Box-and-whisker plot of CypB concentrations in each phase. (b) Box-and-whisker plot of CypD concentrations in follicular, periovulatory and mid-luteal phases. Cyps concentrations were determined by ELISA kits (n = 11). Statistical differences were analysed with Friedman and Dunn-Bonferroni tests, **p < 0.01.