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| 2. |
- Aghajanova, Lusine, et al.
(författare)
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Disturbances in the LIF pathway in the endometrium among women with unexplained infertility
- 2009
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 91:6, s. 2602-2610
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the expression of leukemia inhibitory factor (LIF), its receptors LIFR and gp130, and its inhibitor SOCS1 in endometria from fertile women and infertile women with unexplained infertility. Signaling through the LIF pathway is involved in maintenance of a receptive state of human endometrium. Impaired endometrial receptivity may be a cause of female infertility. DESIGN: Prospective clinical study. SETTING: Hospital-based IVF unit and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-six healthy fertile women and 14 women with unexplained infertility. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Pinopode formation, expression of LIF, LIFR, gp130, and SOCS1 protein and mRNA in endometrial biopsies. RESULT(S): The expression of LIFR in the endometrium was negatively correlated to the expression of SOCS1 and positively correlated to the formation of pinopodes. In control fertile women, simultaneous intense apical staining of LIFR and gp130 together with faint SOCS1 staining was observed in epithelial cells, whereas the opposite was seen in most women with unexplained infertility. CONCLUSION(S): Unexplained infertility in some women might be explained by disturbances in the LIF pathway in midsecretory-phase endometrium.
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| 3. |
- Aghajanova, Lusine, et al.
(författare)
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HB-EGF but not amphiregulin or their receptors HER1 and HER4 is altered in endometrium of women with unexplained infertility
- 2008
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 15:5, s. 484-92
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-binding, epidermal growth factor-like growth factor (HB-EGF) and its receptors (HER I and HER4) play a role in the human implantation process. Amphiregulin is a member of the EGF family but with unknown function in human fertility. It has been suggested that some women with unexplained infertility have defective endometrial development. The aim of this study is to determine the presence of amphiregulin and the receptors HER1 and HER4 in normal human endometrium throughout the menstrual cycle. In addition) the present study aims to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of HB-EGF, HER 1, HER4, and amphiregulin. The stromal staining of HER I and the epithelial staining of HER4 were most intense in the mid- and late-secretory-phase endometrium. Amphiregulin did not vary during the menstrual cycle. In the mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility versus normal endometrium and endometrium from women with malefactor infertility. HB-EGF and HER4 mRNA expression in mid-secretory endometrium of women with unexplained and malefactor infertility were increased compared with normal controls. Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility.
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| 4. |
- Aghajanova, Lusine, et al.
(författare)
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Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology
- 2011
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 95:1, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the expression, distribution, and function of thyroid-stimulating hormone receptor (TSHR) and thyroid hormone receptors (TR) alpha1, alpha2, and beta1 in human endometrium. DESIGN: Experimental clinical study. SETTING: University hospital. PATIENT(S): 31 fertile women. INTERVENTION(S): Endometrial biopsy samples obtained throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Real-time reverse transcriptase polymerase chain reaction, immunohistochemistry and Western blot to study the expression of TSHR, TRalpha1, TRalpha2, and TRbeta1 messenger RNA (mRNA) and proteins in human endometrium. RESULT(S): We found TSHR, TRalpha1, TRalpha2 and TRbeta1 mRNA and proteins expressed in human endometrium. Immunostaining for TSHR in the luminal epithelium and TRalpha1 and beta1 in the glandular and luminal epithelium increased statistically significantly on luteinizing hormone (LH) days 6 to 9, coinciding with appearance of pinopodes. Endometrial stromal and Ishikawa cells expressed mRNA for TSHR, TR, and iodothyronine deiodinases 1-3. After 48 hours, TSH significantly increased leukemia inhibitory factor (LIF) and LIF receptor (LIFR) messenger RNA (mRNA) in endometrial stromal cells, but decreased their expression in Ishikawa cells. Glucose transporter 1 mRNA was up-regulated by TSH in Ishikawa cells. We found that TSH statistically significantly increased secretion of free triiodothyronine (T(3)) and total thyroxin (T(4)) by Ishikawa cells compared with nonstimulated cells. CONCLUSION(S): Thyroid hormones are directly involved in endometrial physiology.
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| 5. |
- Akram, Frida Hosseini, et al.
(författare)
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Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy
- 2017
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Ingår i: Journal of Women's Health. - : Mary Ann Liebert Inc. - 1540-9996 .- 1931-843X. ; 26:11, s. 1231-1235
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Tidskriftsartikel (refereegranskat)abstract
- Background: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy.Materials and Methods: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n=611), one low-risk group comprising women without risk factors for thyroid disorder (n=511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n=88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed.Results: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p=0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0mIU/L.Conclusions: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since approximate to 10% of women with SCH or hypothyroidism could not be diagnosed in this way.
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| 6. |
- Altmäe, Signe, et al.
(författare)
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Tissue Factor and Tissue Factor Pathway Inhibitors TFPI and TFPI2 in Human Secretory Endometrium - Possible Link to Female Infertility
- 2011
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 18:7, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.
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| 7. |
- Bjuresten, Kerstin, et al.
(författare)
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Luteal phase progesterone increases live birth rate after frozen embryo transfer
- 2011
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 95:2, s. 534-537
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To see if progesterone support has a beneficial effect on live birth rate after frozen embryo transfer in natural cycles. DESIGN: Prospective randomized controlled trial. SETTING: University-based hospital. SUBJECT(S): Four hundred thirty-five women undergoing embryo transfer in natural cycles. INTERVENTION(S): The women received either vaginal progesterone, 400 mg twice a day from the day of embryo transfer in natural cycles, or no progesterone support. MAIN OUTCOME MEASURE(S): Live birth rate, biochemical pregnancy rate, pregnancy rate, and spontaneous abortion rate. RESULT(S): Live birth rate were significantly greater in women receiving vaginal progesterone as luteal phase support after frozen-thawed embryo transfer in natural cycles compared with those who did not take progesterone. There were no differences in biochemical pregnancy rate, pregnancy rate, or spontaneous abortion rate. CONCLUSION(S): Progesterone supplementation improves live birth rate after embryo transfer in natural cycles.
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| 8. |
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| 9. |
- Brundin, Peik M.A., et al.
(författare)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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| 10. |
- Brundin, Peik M., et al.
(författare)
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Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.
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