| 1. |
- 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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| 2. |
- 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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| 3. |
- Aghajanova, Lusine, et al.
(författare)
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Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue
- 2009
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Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 18:3, s. 337-347
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Altmäe, Signe, et al.
(författare)
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Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome : a preliminary report
- 2009
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Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 18:5, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.
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| 5. |
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| 6. |
- Ha, Chunfang, et al.
(författare)
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Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 2:1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (>= 80 ml per menstruation) and 12 women with normal blood loss (<80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p<0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.
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| 7. |
- Hildenbrand, Anna, et al.
(författare)
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Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment.
- 2008
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Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 22:1, s. 49-53
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporin-1 (AQP1) is involved in the angiogenesis and structural modifications of microvessels and possibly also in the pathogenesis of idiopathic menhorrhagia, where a reduced AQP1 expression is seen in the endometrium. Mifepristone treatment induces reduced menstrual bleeding and amenorrhea and also has a direct effect on endometrial arterioles. Administered with gestagen-only contraceptive methods, antiprogestins improve the bleeding pattern. The objective of this study was to evaluate the AQP1 expression in endometrial blood vessels during normal cycle and after mifepristone treatment. Localization and expression of AQP1 was determined using immunohistochemistry and reverse transcriptase chain reaction (RT-PCR) in 43 biopsies from human endometrium taken during a normal cycle and after mifepristone treatment. AQP1 expression in human endometrial vessels is not cycle dependent and is stronger in capillaries and arteries than in veins. After mifepristone treatment the staining intensity was increased, but not the number of stained vessels. The presence of AQP1 was also confirmed using RT-PCR. The changes in AQP1 expression could contribute to the reduced bleeding seen following mifepristone treatment and could be an effect of either antagonizing progesterone or cortisol.
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| 8. |
- Rajareddy, Singareddy, 1977-
(författare)
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Studies of phosphatidylinositol 3 kinase (PI3K) signaling pathway in mammalian ovarian follicle activation and development
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intra-oocyte signaling pathways that control oocyte growth and early follicular development are largely unknown. The aim of this thesis was to investigate the regulation and functions of phosphatidylinositol 3 kinase (PI3K) pathway in the oocyte, focusing in the roles of Foxo3a, p27, and Pten (phosphatase and tensin homolog deleted on chromosome ten). The physiological significance of Foxo3a in oocytes had been investigated by generating a transgenic mouse, whereby constitutively active Foxo3a is maintained in oocytes using the oocyte-specific ZP3 (Zona pellucida) promoter. The expression of the constantly active “negative” molecule Foxo3a in mouse oocytes was found to cause retardation of oocyte growth, resulting in a significant reduction in oocyte volume in secondary follicles. The transgenic mice also showed arrested follicular development and were infertile. In addition, when Foxo3a was overexpressed in oocytes of primary follicles, oocyte growth and follicular development were retarded. One of the causes of this phenotype may be the retained expression of the cyclin-dependent kinase (Cdk) inhibitor 1B (Cdkn1b), commonly known as p27kip1 or p27, in the nuclei of oocytes. The role and related mechanisms of p27 in controlling early follicular development and oocyte growth were then investigated using wild-type and p27-deficient (p27-/-) mice, and we demonstrated that (i) p27 suppresses follicle endowment/formation and activation, (ii) p27 induces follicle atresia that occurs prior to sexual maturity, and (iii) the overactivated follicles in p27-/- ovaries are depleted in early adulthood, causing premature ovarian failure (POF). In this thesis, we also provide genetic evidence that in mice with conditional deletion of Pten a major negative regulator of PI3K in oocytes, the entire pool of primordial follicles becomes activated, and subsequently all activated follicles are depleted in young adulthood, causing POF. Further mechanistic studies revealed that loss of Pten in oocytes resulted in elevated Akt signaling, which led to upregulation of both expression and activation of ribosomal protein S6 (rpS6) in oocytes. The results thus show that the mammalian oocyte serves as the headquarters of programming of the occurrence of follicle activation, and that the PI3K pathway of the oocyte governs follicle activation through control of initiation of oocyte growth.
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| 9. |
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| 10. |
- Wånggren, Kjell, et al.
(författare)
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Regulation of muscular contractions in the human Fallopian tube through prostaglandins and progestagens
- 2008
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 23:10, s. 2359-68
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transport of gametes and embryos is an important function of the Fallopian tube. Both muscular contractions and cilia activity are involved in the transportation. Prostaglandins (PGs) are known mediators of muscular contractility. PG receptors have previously been demonstrated in the human Fallopian tube. The aim was to study the effect of PGs and progestagens, antiprogestin, hCG and oxytocin on muscular contractions in the human Fallopian tube, and the hormonal regulation of PG receptors. METHODS: Twenty-two healthy women operated for benign causes were included in the study. The ampullary-isthmic junction of the Fallopian tubes was excised and used for in vitro contractility studies. The effect of PGE(1), PGE(2), PGF(2alpha), progesterone, mifepristone, levonorgestrel, oxytocin and hCG on contractility was studied. Explants of Fallopian tubes were cultured for 24 h to study the effect of progestagens and hCG on the expression of PG receptors using immunohistochemistry and real-time PCR. RESULTS: Muscular contractions increased after treatment with PGF(2alpha) and PGE(2) (P < 0.05). The contractions decreased after PGE(1), progesterone, levonorgestrel, mifepristone, oxytocin and hCG (P < 0.05). In tubal explant studies, relative mRNA expression of EP1, EP2, EP3 and FP increased after levonorgestrel treatment (P < 0.05). Mifepristone and levonorgestrel treatment increased immunostaining intensity of EP1 and EP2 protein, in lumen, muscle and vessels. Progesterone and mifepristone increased immunostaining of FP in vessels. CONCLUSIONS: These data suggest that the transport of gametes and embryos involves the action of PGs, progesterone, oxytocin and hCG on muscular contractility.
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