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. 2013 May 22;8(5):e64807.
doi: 10.1371/journal.pone.0064807. Print 2013.

Systemic inflammation is associated with ovarian follicular dynamics during the human menstrual cycle

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Systemic inflammation is associated with ovarian follicular dynamics during the human menstrual cycle

Kathryn B H Clancy et al. PLoS One. .

Abstract

Background: Ovarian processes and the timing of ovulation are important predictors of both female fertility and reproductive pathology. Multiple waves of antral follicular development have been documented during the menstrual cycle in women. However, the mechanisms underlying the development of follicular waves and their clinical significance are not fully understood. The objective of this study was to examine the relationship between C-reactive protein (CRP) and follicular waves in healthy women. We wanted to determine whether follicular wave dynamics influence systemic inflammation, as ovarian activity increases local inflammatory processes and blood flow. We tested the hypothesis that women with 3 follicular waves would have higher CRP concentrations than those with 2 waves. We further hypothesized that a greater number of major waves (those with a dominant follicle) would be positively associated with CRP.

Methods/principal findings: Thirty-nine healthy women underwent daily transvaginal ultrasound examinations for one interovulatory interval, as part of an earlier study. Serum was collected every 3 days during the interovulatory interval (IOI). Enzyme-linked immunosorbent assays were conducted to quantify serum CRP concentrations. Women with 3 waves had higher average log CRP concentrations (n = 14, -0.43±0.35) over the IOI than those with 2 waves (n = 25, -0.82±0.47, p = 02). Average log CRP concentrations were greater in women with 3 (0.30±0.31) versus 1 (-0.71±0.55) or 2 (-0.91±0.47) major waves (p = 0.03). Greater average CRP over the IOI was attributed to greater CRP in the follicular, but not the luteal phase, of the IOI.

Conclusions/significance: A greater number of total antral follicular waves, in particular major waves, corresponded to greater serum concentrations of CRP. These findings suggest that women with a greater number of follicular waves exhibit greater tissue remodeling and therefore greater local and systemic inflammation.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mean CRP concentrations over the IOI in women with two or three follicle waves.
Non-transformed data are shown as the mean ± SEM.
Figure 2
Figure 2. Mean CRP concentrations over the IOI in women with different patterns of major and minor follicle development.
Two waves: −+ and ++; three waves: −−+, −++ and +++. Non-transformed data are shown as the mean ± SEM.
Figure 3
Figure 3. Mean CRP concentrations over the IOI in women with one, two or three major waves, irrespective of total number of waves.
Non-transformed data are shown as the mean ± SEM.
Figure 4
Figure 4. CRP concentrations across the IOI in women with two versus three follicle waves.
Non-transformed data are shown.
Figure 5
Figure 5. Follicle diameter and CRP concentrations are aligned by menses through the IOI to determine potential time-dependence of relationships between follicular waves and inflammation.
A) Mean follicle diameter in women with 1, 2 and 3 major waves. B) CRP concentrations in women with 1, 2 and 3 major waves. Non-transformed data are shown.

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