1. |
- Bourlev, Vladimir, et al.
(author)
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Different proliferative and apoptotic activity in peripheral versus central parts of human uterine leiomyomas
- 2003
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In: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 0378-7346 .- 1423-002X. ; 55:4, s. 199-204
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To determine whether there are differences in proliferative and apoptotic activity and in expression of sex steroid receptors between central and peripheral parts of human uterine leiomyomas in different menstrual cycle phases.METHODS:Biopsy specimens of the myometrium and peripheral and central parts of uterine leiomyomas were obtained from 15 women in the proliferative phase and 8 women in the secretory phase. Mitotic cells were detected by immunohistochemical staining for Ki67. Apoptotic cells were detected by the TUNEL method. Mitotic and apoptotic indexes were calculated. Tissue levels of oestrogen and progesterone receptors were measured using a commercial monoclonal receptor enzyme immunoassay kit.RESULTS:During the secretory phase the mitotic index was significantly higher in the peripheral than in the central parts of the leiomyomas. During the proliferative phase the apoptotic index was significantly higher in the peripheral compared with the central parts. These differences were not reflected by differences in receptor expression.CONCLUSIONS:The results of this study suggest that the growth of a human uterine leiomyoma mainly occurs in the peripheral parts of the tumour, during the secretory phase of the menstrual cycle. The findings emphasise the importance of being consistent when taking samples for research work.
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2. |
- Bäcklin, B-M, et al.
(author)
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Histology of uterine leiomyoma and occurrence in relation to reproductive activity in the Baltic gray seal (Halichoerus grypus).
- 2003
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In: Veterinary pathology. - 0300-9858 .- 1544-2217. ; 40:2, s. 175-180
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Journal article (peer-reviewed)abstract
- A high prevalence of uterine leiomyoma has been reported in Baltic gray seals aged 15 years and above. Studies on Baltic seals during the 1970s revealed high tissue concentrations of the organochlorines bis(chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), lowered reproduction rate, and pathologic changes. In the second half of the 1970s, decreases of PCB and DDT in Baltic biota occurred, and the prevalence of pregnancies in Baltic seals increased. Between 1975 and 1997, 53 Baltic gray seal females of age 15-40 years were found dead and sent to the Swedish Museum of Natural History. Seals were autopsied and 34/53 (64%) had uterine leiomyomas. Samples from 15 were sufficiently well preserved for histologic examination. Uterine leiomyomas were found most commonly in the uterine corpus but also were observed in the uterine horns, cervix, and vagina. Cut surfaces of the leiomyomas appeared as whorled white fibrous tissue. Histologically, spindle cells were arranged in a whorl-like pattern. The nuclei were rod-like and strikingly uniform in shape and size. Mitotic figures were rare. Immunohistochemical staining of the tumors showed a positive reaction to antibodies recognizing smooth muscle actin. Reproductively active gray seals have an ovarian corpus luteum or albicans for most of the year. In 22/34 (65%) gray seals with uterine leiomyomas, ovaries did not contain corpora. In gray seals without macroscopically detected uterine leiomyoma, ovaries from 6/19 (32%) seals had no corpora. It is possible that the development of leiomyoma in the seals is associated with organochlorines and the previous low reproductive activity.
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3. |
- Ciray, H N, et al.
(author)
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Presence and localization of connexins 43 and 26 in cell cultures derived from myometrial tissues from nonpregnant and pregnant women and from leiomyomas
- 2000
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In: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 182:4, s. 926-930
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Our objective was to study the appearance and distribution of connexins 43 and 26 in various human myometrial cell cultures.STUDY DESIGN:Scrape loading, Western blotting, and immunohistochemical techniques were applied to cultured cells derived from myometrial tissues obtained from nonpregnant and pregnant women (upper and lower uterine segments) and from leiomyomas (tumor and analogous myometrial tissues).RESULTS:Scrape loading revealed the presence of metabolic coupling in all tissues. Indirect immunohistochemical studies showed membrane localization of connexin 43 in all myometrial cultures. Western blots and indirect immunohistochemical studies showed the presence and localization of the connexin 26 protein and associated gap junctions in tissues from myomas and from nonpregnant and pregnant women except for those derived from the upper segment of the pregnant uterus.CONCLUSION:These results show that human myometrial cultures express various gap junction proteins and that there are regional differences in expression of connexins in tissues from pregnant women.
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4. |
- Fu, X, et al.
(author)
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Oxytocin-induced oscillations of cytoplasmic Ca2+ in human myometrial cells.
- 2000
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In: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349 .- 1600-0412. ; 79:3
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Journal article (peer-reviewed)abstract
- BACKGROUND: To investigate the mechanisms of oxytocin (OT) induced oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) in cultured human myometrial cells.METHODS: [Ca2+]i was measured in individual myometrial cells by dual wavelength spectrophotofluorometry using the fluorescent indicator fura-2. Myometrium was obtained at abdominal hysterectomy (n=8) and during cesarean section (n=7).RESULTS: OT (10-300 nM) typically induced [Ca2+]i oscillations with frequencies in the 0.6-0.8/min range. There were no obvious differences in the responses of cells taken from non-pregnant and term pregnant women. The frequency and amplitude of the oscillations were not significantly affected by OT concentrations up to 300 nM. The amplitude of the oscillations decreased in the presence of the voltage-dependent Ca2+ channel antagonist verapamil and gradually disappeared in Ca2+-free medium. The oscillations were further blocked by the inorganic Ca2+ antagonist La3+ and by the intracellular Ca2+-ATPase inhibitor 2.5-di-tert-butylhydroquinone (DTBHQ). Caffeine inhibited the OT-induced oscillations in a concentration-dependent manner. DTBHQ and high concentrations of OT made [Ca2+]i remarkably sensitive to changes in the external Ca2+ concentration.CONCLUSIONS: The results indicate that OT-induced [Ca2+]i oscillations in human myometrial cells are due to inositol 1,4,5-trisphosphate-mediated release of intracellular Ca2+ combined with capacitative as well as voltage-dependent influx of the ion.
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5. |
- Möller, B, et al.
(author)
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Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle
- 2001
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In: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 7:1, s. 65-72
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Journal article (peer-reviewed)abstract
- Angiogenesis is an important but poorly understood process of the cycling endometrium. Endometrial angiogenesis is believed to be regulated by angiogenic growth factors under the influence of ovarian steroids. Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2, fibroblast growth factor 2 (FGF-2) and its receptors FGFR-1 and FGFR-2, as well as epidermal growth factor (EGF) and its receptor EGFR are believed to be important in the control of angiogenesis in the human endometrium. Their expression was examined by immunohistochemistry in endometrial biopsies obtained from 16 healthy women with proven fertility. Western blot analysis showed that the primary antibodies used were specific for their epitopes. We found that VEGF, FGF-2, EGF and their receptors were all expressed, especially in and/or around blood vessels, thus supporting the hypothesis that these peptides contribute to the regulation of angiogenesis and blood vessel function in the human endometrium. The receptors VEGFR-1, VEGFR-2, FGFR-2 and EGFR were co-expressed and exhibited their strongest expression during the beginning of the secretory phase, coinciding with the developing endometrial oedema and formation of a complex subepithelial capillary plexus. No correlation was seen between receptor expression and stromal blood vessel density.
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6. |
- Olovsson, Matts, 1958-, et al.
(author)
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Human uterine myocytes retain their energy charge with No gross alterations in morphology for at least 8 days when cultured under anaerobic conditions
- 2000
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In: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 0378-7346 .- 1423-002X. ; 49:3, s. 165-169
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To investigate the ability of human uterine myocytes to grow under anaerobic conditions for a prolonged time period.METHODS:Cells were isolated from fundal myometrium and cultured until subconfluency. The cell type was confirmed by immunostaining for the smooth muscle cell-specific cytoskeletal proteins alpha-actin and desmin. Some cells were further cultured under aerobic conditions and others under anaerobic conditions. Cells were harvested after 0, 4 and 8 days in culture and analyzed for their content of adenylates.RESULTS:Immunostaining revealed that all three preparations contained almost only smooth muscle cells. Energy charge of the myocytes was 0.88 on average at the beginning of the culture experiment. A moderate decrease was noted on day 4 for myocytes grown under both aerobic and anaerobic conditions and no further decrease was noted between days 4 and 8. Morphologically the cells retained their normal appearance and they seemed healthy for at least 8 days in culture under both aerobic and anaerobic conditions.CONCLUSIONS:The results of this study suggest that human myometrial cells can survive for an extended period of time under in vitro conditions regardless of oxygen availability for energy metabolism. This means that anaerobic energy metabolism is enough to sustain vital processes during that period of time.
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7. |
- Wu, Xuxia, et al.
(author)
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Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause
- 2000
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 79:5, s. 397-404
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Journal article (peer-reviewed)abstract
- BACKGROUND:Cell proliferation, apoptosis and expression of p53 proteins were studied in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause.METHODS:Expression of ki-67 and p53 was analyzed by immunohistochemistry and by immunoblotting. Apoptosis was detected by in situ 3' end labelling of cells with DNA fragmentation.RESULTS:In both the proliferative and the secretory phases, ki-67 expression was higher in leiomyomas than in myometrium and both tissues showed higher expression in the secretory than in the proliferative phase. No difference in apoptotic index was observed between leiomyomas and myometrium or between the proliferative and secretory phases. After menopause, the expression of ki-67 as well as the apoptotic index was lower than in the proliferative and secretory phases and no significant difference between tissues was seen. Both leiomyomas and myometrium showed negative staining for p53. Immunohistochemical results regarding p53 were confirmed by Western blot.CONCLUSIONS:Our findings indicate that sex steroids influence the growth of leiomyomas by stimulating cell proliferation rather than by affecting apoptosis. The rate of cell proliferation is higher in fertile age than after menopause and appears to be enhanced under the influence of progesterone.
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