Dataset Information

The cytokine profile of menstrual blood.

ABSTRACT:

Introduction

The menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient. Menstrual blood is easily accessible and provides a source to study menstrual cycle physiology. This study aimed to determine the cytokine profile in menstrual blood plasma and investigate the differences in cytokine profiles between menstrual and peripheral blood plasma. Several previous studies indicate an improved chance of embryo implantation after endometrial scratching. Consequently, our secondary aim was to compare the menstrual blood cytokine profile before and after luteal phase endometrial scratching.

Material and methods

Nineteen healthy donors collected menstrual blood for the first 24 hours of menstruation in two sequential cycles. Matched peripheral blood was taken at the same time. An endometrial biopsy was performed at cycle day 7-9 post ovulation in between the two collection times. A Luminex multiplex assay was performed in one batch analyzing a predetermined group of cytokines in plasma.

Results

Peripheral blood plasma and menstrual blood plasma showed substantial significant differences in cytokine profile. In menstrual blood plasma, C5/C5a, interleukin-6 (IL-6), IL-1?, and CXCL8 were detected in high concentrations, whereas IL-2, IL-12p70, XCL1/Lymphotactin, and interferon-? were low. The most pronounced median differences between menstrual and peripheral blood plasma were found for IL-6, IL-1?, and CXCL8. The cytokine profiles of menstrual blood plasma were similar between the individual donors and did not differ over two subsequent cycles. None of the cytokines analyzed in menstrual blood plasma differed significantly before or after luteal phase endometrial scratching (P < .01).

Conclusions

Our results demonstrate that the menstrual blood cytokine profile is distinctly different from peripheral blood plasma and that the inter-individual difference in menstrual blood cytokine profile in healthy donors is limited and stable over time. The small injury caused by an endometrial biopsy does not change the cytokine profile in the subsequent menstrual cycle. Our study provides new insights into menstrual cycle physiology.

SUBMITTER: Crona Guterstam Y

PROVIDER: S-EPMC7891423 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

The cytokine profile of menstrual blood.

Crona Guterstam Ylva Y Strunz Benedikt B Ivarsson Martin A MA Zimmer Christine C Melin Anna-Sofia AS Jonasson Aino F AF Björkström Niklas K NK Gidlöf Sebastian Brusell SB

Acta obstetricia et gynecologica Scandinavica 20200924 2

<h4>Introduction</h4>The menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient. Menstrual blood is easily accessible and provides a source to study menstrual cycle physiology. This study aimed to determine the cytokine profile in menstrual blood ...[more]

PMID: 32892344

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Project description:Menstruation is the expulsion of the endometrial lining of the uterus following a nearly month long preparation for embryo implantation and pregnancy. Increasingly, the health of the endometrium is being recognized as a critical factor in female fertility, and proteomes and transcriptomes from endometrial biopsies at different stages of the menstrual cycle have been studied for both diagnostic and therapeutic purposes (1 Kao, L. C., et al. 2003 Endocrinology 144, 2870-2881; Strowitzki, Tet al. 2006 Hum. Reprod. Update 12, 617-630; DeSouza, L., et al. 2005 Proteomics 5, 270-281). Disorders of the uterus ranging from benign to malignant tumors, as well as endometriosis, can cause abnormal menstrual bleeding and are frequently diagnosed through endometrial biopsy (Strowitzki, Tet al. 2006 Hum. Reprod. Update 12, 617-630; Ferenczy, A. 2003 Maturitas 45, 1-14). Yet the proteome of menstrual blood, an easily available noninvasive source of endometrial tissue, has yet to be examined for possible causes or diagnoses of infertility or endometrial pathology. This study employed five different methods to define the menstrual blood proteome. A total of 1061 proteins were identified, 361 were found by at least two methods and 678 were identified by at least two peptides. When the menstrual blood proteome was compared with those of circulating blood (1774 proteins) and vaginal fluid (823 proteins), 385 proteins were found unique to menstrual blood. Gene ontology analysis and evaluation of these specific menstrual blood proteins identified pathways consistent with the processes of the normal endometrial cycle. Several of the proteins unique to menstrual blood suggest that extramedullary uterine hematopoiesis or parenchymal hemoglobin synthesis may be occurring in late endometrial tissue. The establishment of a normal menstrual blood proteome is necessary for the evaluation of its usefulness as a diagnostic tool for infertility and uterine pathologies. Identification of unique menstrual blood proteins should aid the forensic community in distinguishing menstrual blood from circulating blood.

Project description:Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥ 2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.

Project description:BACKGROUND: Abnormal uterine bleeding is often investigated in clinical studies and critical to identify during gynecological consultation. The current standard for quantification of menstrual blood loss is the alkaline-hematin-method. However, this method is expensive and inconvenient for patients. Bleeding diaries, although widely used, provide only qualitative information on menstrual blood loss. Other methods have been developed, but still do not provide reliable quantitative data. METHODS: We estimated blood loss volume using data from two clinical studies in women suffering abnormal menstrual bleeding. These estimations were derived from mixed linear models based on diary data, hematological parameters and age. To validate the models, we applied our results to data from a third study with a similar patient population. RESULTS: The resulting best fitting model uses diary entries on bleeding intensity at a particular day, information on occurrence and frequency of single bleeding intensities in defined time windows, hemoglobin and ferritin values and age of the patient all as predictors of menstrual blood loss volume. Sensitivity and specificity for the diagnosis of excessive bleeding were 87% and 70%, respectively. Our model-based estimates reflect the subjective assessment by physicians and patients in the same way as the measured values do.When applying the model to an independent study, we found a correlation of 0.73 between estimated and measured values for the blood loss in a single day. Further models with reduced number of parameters (simplified for easier practical use) still showed correlation values between 0.69 and 0.73. CONCLUSIONS: We present a method for estimating menstrual blood loss volume in women suffering from prolonged or excessive menstrual bleeding. Our statistical model includes entries from bleeding diaries, laboratory parameters and age and produces results which correlate well with data derived by the alkaline-hematin-method. Therefore, this model may be used to estimate menstrual blood loss volume in both routine gynecological counseling and clinical studies.

Dataset Information

The cytokine profile of menstrual blood.

Introduction

Material and methods

Results

Conclusions

Publications

The cytokine profile of menstrual blood.

Similar Datasets

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