| 1. |
- Aghajanova, Lusine, et al.
(author)
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Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue
- 2009
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In: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 18:3, s. 337-347
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Journal article (peer-reviewed)abstract
- Dysfunction in thyroid regulation can cause menstrual and ovulatory disturbances, the mechanism of which is not clear. The distribution and activity of the thyroid-stimulating hormone (TSHR), and the thyroid hormone receptors (TR) alpha1, alpha2 and beta1 in human ovarian tissue and in granulosa cells was studied using immunohistochemistry, reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and immunoassays. Strong immunostaining of TSHR, TRalpha1 and TRbeta1 was observed in ovarian surface epithelium and in oocytes of primordial, primary and secondary follicles, with minimal staining in granulosa cells of secondary follicles. Granulosa cells of antral follicles expressed TSHR, TRalpha1 and TRbeta1 proteins. Messenger RNA for all receptors was present in ovarian tissue. Mature human granulosa cells expressed transcripts for 5' deiodinases types 2 and 3, but not type 1, indicating the possibility of conversion of peripheral thyroid hormone thyroxin (T(4)). Granulosa cells stimulated with TSH showed a significant increase in cAMP concentrations after 2 h of culture (P = 0.047), indicating activation through TSHR. Stimulation with T(4) resulted in increased extracellular signal-regulated kinase 1 and 2 activation after 10, 30, 60 min and 24 h. These data demonstrate that TSH and thyroid hormone receptors may participate in the regulation of ovarian function.
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| 2. |
- Aghajanova, Lusine, et al.
(author)
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Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology
- 2011
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 95:1, s. 230-237
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Journal article (peer-reviewed)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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| 3. |
- Granfors, Michaela, 1972-, et al.
(author)
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Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage : A retrospective case control study.
- 2012
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 121-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p = 0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01 - 2.64, p = 0.045) and G/G (AOR 1.52, 95% CI 1.02 - 2.27, p = 0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.
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| 4. |
- Haroun, Sally, et al.
(author)
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Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion
- 2014
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In: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 29:6, s. 737-44
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Journal article (peer-reviewed)abstract
- Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.
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