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Influence of Hormonal Contraceptives on the Immune Cells and Thickness of Human Vaginal Epithelium
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
2003 (Engelska)Ingår i: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 102, nr 3, s. 571-582Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: To determine whether use of steroid hormone contraceptives modifies immune defense parameters of the vaginal epithelium in humans. METHODS: Vaginal biopsies were collected during the follicular and luteal phases in regularly menstruating women (controls) and in women using combined oral contraceptives, depot-medroxyprogesterone acetate injections, or levonorgestrel implants. Fifteen healthy women (aged 20-34 years) were enrolled in each group. Biopsies were analyzed in a blinded manner. Epithelial thickness was estimated by morphometry. Immune cells were analyzed by immunomorphometry with cell-type-specific monoclonal antibodies. RESULTS: The epithelium of controls harbored 241+/-35 leukocytes (CD45+ cells) per mm2 (mean+/-1 standard error of the mean), and the thickness was 261+/-16 microm. T lymphocytes (CD3+) dominated, and cytotoxic or suppressor T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7+/- 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes, and granulocytes were generally absent. There were no significant differences between the follicular and luteal phases. The epithelium was significantly thicker in all three groups that used hormonal contraceptive (333+/-9 microm) compared with controls, and it exhibited superficial hyperplasia. The frequency of intraepithelial leukocytes (CD45+) was increased in depot-medroxyprogesterone acetate (P<.001) and levonorgestrel implant users (P<.04). In depot-medroxyprogesterone acetate users, this was explained by an increased frequency of the CD8+ T lymphocyte subset. CONCLUSION: Hormonal contraceptives induce hyperplasia of the vaginal epithelium. The significant changes in the intraepithelial leukocyte population in depot-medroxyprogesterone acetate and levonorgestrel implant users most probably reflect altered local immune capacity.

Ort, förlag, år, upplaga, sidor
2003. Vol. 102, nr 3, s. 571-582
Nationell ämneskategori
Reproduktionsmedicin och gynekologi
Identifikatorer
URN: urn:nbn:se:umu:diva-4689DOI: 10.1016/S0029-7844(03)00618-5PubMedID: 12962945OAI: oai:DiVA.org:umu-4689DiVA, id: diva2:143899
Tillgänglig från: 2005-09-22 Skapad: 2005-09-22 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Human vaginal epithelial immunity and influences of hormonal contraceptive usage
Öppna denna publikation i ny flik eller fönster >>Human vaginal epithelial immunity and influences of hormonal contraceptive usage
2005 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The vagina is the port of entry for sexually transmitted diseases in women. Its epithelium constitutes the luminal border, thus comprising an important defence barrier. The objective of this work was to investigate the mechanisms of importance in the immune defence of the vaginal epithelium of healthy, fertile women, and possible menstrual cycle changes. Effects of hormonal contraceptive usage on oestrogen receptor (ER) and progesterone receptor (PR) expression were studied. The contribution of epithelial cell to the immune defence was estimated by assaying their expression of antimicrobial defensins and the epithelial thickness.

Vaginal biopsies and serum samples were collected during the follicular and luteal phases in regularly menstruating women (controls) and in users of combined oral contraceptives (COCs), levonorgestrel implants (LNGs), or depot-medroxyprogesterone acetate injections (DMPAs). Fifteen healthy women (aged 20–34 years) were enrolled in each group. Morphometry was performed on vaginal tissue stained with haematoxylin/eosin and by immunohistochemistry using monoclonal antibodies against immune cell markers, PR, and ER. Expression of mRNA for human α-defensins HD-5 and HD-6, and human β-defensins (HBD) 1 to 4 were determined by real-time qRT-PCR and in situ hybridization.

In controls, the epithelium was 261 ± 16 μm thick and harboured 241 ± 35 leukocytes (CD45+) per mm2. T lymphocytes (CD3+) dominated. Both αβ T cells and γδ T cells were present with an approximate 4-fold dominance of αβ T cells. Cytotoxic T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7 ± 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes and granulocytes were generally absent. No differences were found between the follicular and luteal phase. All four β-defensins analysed for were detected in vaginal epithelium and most samples expressed at least two. HBD-2 and HBD-3 were most frequent. HBD-3 and HBD-4 expressing cells were localized in the parabasal and intermediate cell layers. α-defensins were not detected.

The epithelium was significantly thicker (333 ± 9 μm) in COC, LNG, and DMPA users than in controls, and commonly showed hyperplasia. In DMPA and LNG users the frequency of intraepithelial leukocytes (CD45+) was increased, explained by increased frequencies of both αβ and γδ T cells. In DMPA users there was also a selective increase in CD8+ T cells. PR expression was significantly reduced in DMPA users compared with controls, COC and LNG users. COC and particularly DMPA users often had undetectable levels of serum E2.

In conclusion, both adaptive immunity, i.e. intraepithelial T cells, and innate defence mechanisms, i.e. intraepithelial macrophages and β-defensins, are believed to contribute to the immune defence in the human female lower genital tract. These parameters did not change during the menstrual cycle but hormonal contraceptive usage, especially DMPA, affected the quality of the epithelium. The use of DMPA and LNG was correlated with the accumulation of T cells within the epithelium. The effects of these changes on the risk of contracting infections are yet to be determined.

Ort, förlag, år, upplaga, sidor
Umeå: Klinisk mikrobiologi, 2005. s. 92
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 977
Nyckelord
human vaginal epithelium, hormonal contraceptives, epithelial thickness, intraepithelial immune cells, steroid receptors, steroid hormones, defensins
Forskningsämne
obstetrik och gynekologi
Identifikatorer
urn:nbn:se:umu:diva-595 (URN)91-7305-923-4 (ISBN)
Disputation
2005-10-07, Föreläsningssal A 103 (Astrid Fagraeus salen), byggnad 6A, våning 1, Norrlands Universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Tillgänglig från: 2005-09-22 Skapad: 2005-09-22 Senast uppdaterad: 2009-11-16Bibliografiskt granskad

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Hammarström, Marie-Louise

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