Inducible heat shock protein A1A (HSPA1A) is markedly expressed in rat myometrium by labour and secreted via myometrial cell-derived extracellular vesicles.

The myometrium goes through physiological, cellular and molecular alterations during gestation that necessitate effective cellular proteostasis. Inducible heat shock protein A1A (HSPA1A) is a member of the 70-kDa heat shock protein A (HSPA) family, which acts as a chaperone to regulate proteostasis; however, HSPA1A also participates as a cytokine in inflammatory regulation, leading to its designation as a chaperokine. This study examined the spatiotemporal expression of HSPA1A protein in the rat myometrium throughout gestation and assessed whether it is secreted as cargo of myometrial cell-derived extracellular vesicles (EVs). Immunoblot analysis demonstrated that HSPA1A expression was markedly elevated during late pregnancy and labour and increased by uterine distension. Myometrial HSPA1A expression insitu increased in myocytes of longitudinal and circular muscle layers from Day 19 through to postpartum, specifically in the cytoplasm and nuclei of myocytes from both muscle layers, but frequently detectable just outside myocyte membranes. Scanning electron microscopy examination of samples isolated from hTERT-HM cell-conditioned culture medium, using EV isolation spin columns, confirmed the presence of EVs. EV lysates contained HSPA8, HSPA1A and the EV markers apoptosis-linked gene 2-interacting protein X (Alix), the tetraspanin cluster of differentiation 63 (CD63), tumour susceptibility gene 101 (TSG101) and HSP90, but not the endoplasmic reticulum protein calnexin. These results indicate that HSPA1A may act as a chaperokine in the myometrium during pregnancy.

Decrease in SHP-1 enhances myometrium remodeling via FAK activation leading to labor.

Preterm birth is one of the most common complications during human pregnancy and is associated with a dramatic switch within the uterus from quiescence to contractility. However, the mechanisms underlying uterine remodeling are largely unknown. Protein kinases and phosphatases play critical roles in regulating the phosphorylation of proteins involved in the smooth muscle cell functions. In the present study, we found that Src-homology phosphatase type-1 (SHP-1, PTPN6) was significantly decreased in human myometrium in labor compared with that not in labor. Timed-pregnant mice injected intraperitoneally with the specific SHP-1 inhibitor protein tyrosine phosphatase inhibitor I (PTPI-1) manifested significantly preterm labor, with enriched plasmalemmal dense plaques between myometrial cells and increased phosphorylation at Tyr397 and Tyr576/577 sites of focal adhesion kinase (FAK) in myometrial cells, which remained to the time of labor, whereas the phosphorylation levels of ERK1/2 and phosphatidylinositol 3 kinase (PI3K) showed a rapid increase upon PTPI-1 injection but fell back to normal at the time of labor. The Tyr576/577 in FAK played an important role in the interaction between FAK and SHP-1. Knockdown of SHP-1 dramatically increased the spontaneous contraction of human uterine smooth muscle cells (HUSMCs), which was reversed by coinfection of a FAK-knockdown lentivirus. PGF2α downregulated SHP-1 via PLCß-PKC-NF-κB or PI3K-NF-κB pathways, suggesting the regenerative downregulation of SHP-1 enhances the uterine remodeling and plasticity by activating FAK and subsequent focal adhesion pathway, which eventually facilitates myometrium contraction and leads to labor. The study sheds new light on understanding of mechanisms that underlie the initiation of labor, and interventions for modulation of SHP-1 may provide a potential strategy for preventing preterm birth.

Simvastatin, at clinically relevant concentrations, affects human uterine leiomyoma growth and extracellular matrix production.

OBJECTIVE: To observe the antifibroid effects of therapeutic concentrations of simvastatin, which interferes with cholesterol biosynthesis, a known precursor of five major classes of steroid hormones, including progesterone and estrogen, which play a major role in the development and growth of uterine leiomyomas. DESIGN: Two-dimensional and three-dimensional cell culture study of immortalized human leiomyoma and patient-matched myometrium cells treated with simvastatin. SETTING: University laboratory. PATIENT(S): None. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Cell proliferation, alteration in apoptotic signaling pathways, and extracellular matrix (ECM) protein production. RESULT(S): Simvastatin demonstrated a concentration-dependent antiproliferative effect on both the leiomyoma cells and the patient-matched myometrium cells, but a higher inhibitory effect at lower concentrations of simvastatin was observed in leiomyoma cells. Simvastatin also regulated leiomyoma cell apoptosis through a concentration-dependent increase in activity of caspase-3. Simvastatin significantly inhibited expression of major ECM proteins collagen I, collagen III, fibronectin, versican, and brevican in leiomyoma cells at concentrations as low as 10-9 mol/L within 48 hours of exposure. CONCLUSION(S): Simvastatin induces apoptosis in uterine leiomyoma cells at low concentrations, as evidenced by increased active caspase levels. Furthermore, inhibited production of the ECM proteins may lead to reduction in tumor size. Simvastatin may represent a novel therapeutic treatment strategy for uterine leiomyomas.

Gold and Female Reproductive Organs: an Ultrastructural Study.

Gold, a heavy yellow-colored metal, is usually found in nature as a metallic element or as salts. This noble metal historically had a reputation as an anti-inflammatory medicine for rheumatoid arthritis, a nervine, and a remedy for nervous disorders, as well as a potential anticancer agent. It has also been used as component in dental restorations and in implant materials. The present study was undertaken to point out histological and ultrastructural effects of gold, administered by intraperitoneal route, in pregnant female reproductive organs (ovary and uterus), in order to clarify its side effects on the reproductive function. Using the transmission electron microscopy (TEM), the ultrastructural investigations of both ultrathin ovarian and uterine sections of treated pregnant rats revealed the existence of numerous heterogeneous clusters with very electron-dense inclusions characterized by various aspects in the lysosomes of granulosa, theca interna cells, and theca externa cells. Degeneration of these tissues, like cell vacuolization, marked expansion of the endoplasmic reticulum, mitochondrial alterations, and necrotic foci, were also highlighted. Moreover, huge phagolysosomes and high numbers of eosinophils as signs of inflammation were also identified especially in endometrial and myometrial cells of gold-treated rats. The ultrastructural investigations of reproductive organ sections of control pregnant rats showed a normal ultrastructural aspect and no loaded lysosomes. These results speculated the toxicity of gold at the used dose. The observed signs of toxicity allowed concluding that the important role of lysosome in the sequestration of this element under an insoluble form in all categories of cells in the studied tissues does not seem to be efficient.

Toxicological effects and ultrastructural changes induced by lanthanum and cerium in ovary and uterus of Wistar rats.

Rare earths have been widely used in a huge number of areas in industry and medicine. Therefore, they exist in the environment and possibly accumulated within the human body. However their effects in the living organism particularly in the female reproductive system are still unclear. In this work, the subcellular behavior of lanthanum and cerium was investigated through the Transmission Electron Microscopy (TEM), in different territories of the reproductive system of Wistar rats exposed intraperitoneally to soluble solution of these elements during 2 weeks. Ultrastructural investigations of ultrathin sections from uterus and ovary of treated rats revealed the existence of inclusions with high electron density and heterogeneous aspects in the lysosomes of uterus and ovary cells. Many disruptions of architecture were observed, accompanied with several changes like vacuolations, significant expansion of the endoplasmic reticulum, mitochondrial alterations and necrotic cells, demonstrating the toxicity of these elements with doses used. Phagolysosomes as well as eosinophils were also seen. Our experimental investigations revealed no intralysosomal inclusions in ultrathin sections of the uterus and ovary of pregnant control females. The original mechanism implicated in this insolubilization-concentration phenomenon of these elements, as non-soluble phosphate form, in the lysosomes is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase.

The effects of retinoic acid on mmp-2 production, proliferation and ultrastructural morphology in rat uterus.

AIMS: Retinoic acid (RA) has a vital importance in order to ensure continuity and morphology in many tissues. Matrix metalloproteinases (MMPs) have significant roles in proliferation, the formation of cancers, and metastasis. In this study the effects of RA on MMP-2 production in cells of rat uterus were investigated. METHODS: Twenty-four adult Spraque Dawley rats were divided into two groups, the experimental group was treated with 40mg/kg/day 13-cis RA for 5days by gavage. Uterine tissue sections were treated with BrdU and MMP-2 antibodies, evaluated using light microscopy. Tissues were fixed with 2.5% glutaraldehyde and evaluated using transmission electron miroscopy. RESULTS: MMP-2 immunoreactivity decreased in the stromal cells compared with the control group and no staining of MMP-2 was observed in glandular epithelium in the experimental group. BrDU labeling of cells showed significant decrease in RA-treated group versus control group cells. Based on the electron microscopy evaluation, the surface epithelial cells of the experimental group showed vacuolization, and an accumulation of lipofuscin bodies was also observed in the gland epithelium. Cells involving autophagic vacuoles contained excess lipid granules in the entire uterus layers especially localized at the border of the endometrium and myometrium. CONCLUSION: RA had negative effects on cell proliferation and cell morphology and inhibited MMP-2 expression.

Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis.

OBJECTIVE: To determine if ultrastructural tissue trauma occurs in the junctional zone in uteri in adenomyosis. DESIGN: A case-control experimental study. SETTING: Endometriosis research center. PATIENT(S): Twelve uteri with adenomyosis, and 9 uteri without adenomyosis, were gained during laparoscopy-assisted vaginal hysterectomy. INTERVENTION(S): Transmission electron microscopic study of the junctional zone, as well as immunohistochemical staining for epithelial cadherin, and van Gieson staining and immunofluorescence for CD45 and CD68. MAIN OUTCOME MEASURE(S): Analysis of the electron microscopy photos and the immunoreactive scores of the staining. RESULT(S): The inner myometrial muscle fibers were diversely arranged in adenomyosis; they were parallel to the basal endometrial glands in nonadenomyosis. Nuclear membrane infolding of the basal glandular epithelium and the disruption of the interface between basal endometrium and inner myometrium in adenomyosis (but not in nonadenomyosis) were evident. Intraepithelial pale cells were seen in the basal endometrial glands in both groups, but they lacked CD45 and CD68 expression. They were seen actively migrating into the stroma in adenomyosis only. CONCLUSION(S): The myofiber disarray in the inner myometrium, and the nuclear membrane irregularities in adenomyosis, are evidence for ultramicro-trauma in adenomyosis. The migrating nonleukocytic pale cells may be involved in pathogenesis of adenomyosis.

[Study of ultrastructural features of myocytes in uterine junctional zone].

OBJECTIVE: To study the ultrastructural features of myocytes in uterine junctional zone (JZ). METHODS: From August 2010 to August 2013, there were 16 pre-menopause patients who suffered from cervical neoplasm to be performed hysterectomy. Samples of JZ and outer myometrium (OM) of hysterectomy specimens were collected. There were 8 specimens from the proliferative-phase and 8 specimens from the secretory-phase of endometrium. Ultrastructural features of JZ and OM were examined by using transmission electron microscopy and the related indices of myocytes were compared by using Student's t test. RESULTS: At JZ, there were more cytoplasmic process in the myocytes. The myocytes of JZ exhibited significant difference compared with those of OM. Firstly, the contractile structural components, such as the dense patches, dense bodies and the myofilaments were less abundant. In contrast, the perinuclear cell organelles were more distinct. The mitochondria, endoplasmic reticulum and Golgi apparatus were more prominent, denoting active protein synthesis. Secondly, the mean diameter of cell and nuclei demonstrated cyclic change. In proliferative phase of endometrium, the cell diameters of JZ and OM were (4.70±0.52) and (4.69±1.20)µm, respectively, which there were no significant difference (P = 0.987). While in secretory phase, the cell diameters of JZ and OM were (3.75±0.36)and (4.92±0.51)µm, which there were significant difference (P = 0.006). In proliferative phase, the nuclei diameters of JZ and OM were (3.24±0.41) and (2.90±0.62)µm, and in secretory phase, the nuclei diameters of JZ and OM were (2.44±0.27) and (2.92±0.44)µm. There were no significantly different in both phases (P = 0.374, P = 0.097). The diameters of cell and nuclei had cyclical changes (P < 0.05). However, the cyclical changes were absent in OM (P > 0.05). Thirdly, the myofilaments/cytoplasm ratio of JZ in proliferative and secretory phases were 0.27±0.04 and 0.34±0.03, which were significantly less than those of OM in respective phases (0.49±0.03 and 0.±0.03; P = 0.000, P = 0.000). The myofilaments/cytoplasm ratio exhibited cyclical changes in JZ (P = 0.029), but in OM, the cyclical changes were absent (P = 0.083). CONCLUSIONS: Compared with OM, ultrastructures associated with synthetic organelles are prominent, whereas the contractile organelles are reduced. And there are the cyclical changes in ultrastructural characteristics. The ultrastructural features of JZ are the basis of its physiology.

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

OBJECTIVE: to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. MATERIAL AND METHODS: Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). RESULTS: The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. CONCLUSION: A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

[Relationship between ultrastructural features of endometrial-myometrial interface and pathogenesis of adenomyosis].

OBJECTIVE: To explore the ultrastructural features of endometrial-myometrial interface (EMI) of adenomyosis and normal myometrium. METHODS: From May 2010 to September 2013, 102 uterine myometrial specimens were obtained from 102 patients undergoing hysterectomy. There were 56 adenomyosis patients as ADS group (including proliferative endometrium, n = 26 and secretory endometrium, n = 30) and another 46 with cervical intraepithelial neoplasis (CIN) III as control group. The myometrium underneath endometrium and the outer third of myometrium were immediately harvested after operation. And the samples were processed and observed under transmission electron microscopy. RESULTS: (1) In the presence of uterine adenomyosis, the nuclei were significantly larger than controls and significantly enlarged with less prominent collagen fibrils. The cytoplasm was abundant, denoting cellular hypertrophy. The rough endoplasmic reticulum and Golgi apparatus became more prominent. But the dense patches and dense bodies appeared similar to the control; (2) EMI myocytes ultrastructure showed cyclic changes in controls. In proliferative cycle, the average nuclear size was larger than that in secretory cycle [(3.24 ± 0.41), (2.44 ± 0.27) µm, P < 0.05]. But there was not any differences from different cyclic phases in adenomyosis [(2.34 ± 0.17), (2.63 ± 0.39) µm, P > 0.05]; (3) EMI myocytes appeared significantly different than that of outer myometrium. The nuclei of EMI myocytes were much smaller than outer myometrium. And there was less prominent collagen fibrils. The dense patches, dense bodies and myofilament-cytoplasm ratio of EMI were smaller than outer myometrium. The nuclei-to-myocyte ratio was larger than outer myometrium. CONCLUSION: Abnormal ultrastructural features of EMI may be correlated with the development of adenomyosis.

Ultrastructural features of endometrial-myometrial interface and its alteration in adenomyosis.

The endometrial-myometrial interface (EMI) is a specific functional region of uterus. However, our knowledge on EMI ultrastructure both in normal uterus and adenomyosis is far from enough to understand its pathology. In this study, used the samples of EMI and outer myometrium (OM) from the adenomyosis hysterectomy specimens and the subjects from the control uteri, we prospectively compared the ultrastructure of myocytes from EMI and OM, the ultrastructural changes of EMI between the proliferative and secretory phases, and the ultrastructural difference of EMI between adenomyosis and the control group. In both adenomyosis and control group, there were differences in ultrastructure between myocytes from EMI and OM. Specifically, the myocytes from EMI were rich in organelles. In contrast, the myocytes from OM had abundant contractile structural components. In the proliferative phase, the myocytes from EMI in adenomyosis had significantly smaller cell and nucleus diameter than those from the control group, but in the secretory phase, the difference was not significant. In the control group, the various ultrastructural features of myocytes from EMI including the mean diameter of cell and nuclei and the myofilaments/cytoplasm ratio exhibited cyclical changes, but in adenomyosis, the normal cyclical changes were absent. In conclusions, there are significant ultrastructural differences between the myocytes from EMI and OM. The myocytes in women with adenomyosis were significantly different to the control subjects, primarily because the normal cyclical changes were absent.

Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: implications for trophoblastic invasion of the placental bed.

AIM: The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis. METHODS: We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 11 women undergoing pregnancy termination in the first trimester. The biopsies were subjected to light, transmission and scanning electron microscopy, and immunohistochemical studies using mouse monoclonal antibodies against cytokeratin 7 and collagen types I, III and V. RESULTS: Collagen fibrils in the stroma of decidua basalis were significantly thicker when compared to those in decidua parietalis (56.48 ± 1.37 nm vs 45.64 ± 0.85 nm; P < 0.0001 [mean ± standard error]) between 9 and 12 weeks gestation, but this difference in thickness was not observed at gestations below 9 weeks. In basalis, the fibrils appeared disrupted at most places surrounding the decidual/trophoblast cells while a uniform regular arrangement was preserved throughout most of parietalis. CONCLUSION: There are differences in the ultrastructure of collagen fibrils between basalis and parietalis, with thicker and disrupted fibrils within abundant amorphous tissue in basalis, and thinner uniform fibrils in parietalis. These differences may reflect an adaptive response by decidua or a direct consequence of the invading trophoblast cells.

Vascular structure of outer myometrial uterine leiomyomata - a preliminary SEM and immunohistochemical study.

AIM: The main goal of this study was assessment of vascular structure of uterine leiomyomata localized between outer myometrium and endometrium. MATERIALS AND METHODS: The study was carried out on thirty two human uteri collected upon autopsy. Vessels were injected with synthetic resin, next corroded and coated with gold, finally observed using scanning electron microscope. Next ten uteri were injected with acrylic emulsion and studies using immunohistochemical staining for von Willebrandt's factor. RESULTS: Vascular structure of outer myometrial leiomyomata was quite similar to those observed in the middle of muscular layer of uterus, characterized by relatively dense 'vascular capsule', consisted of flattened vein, arterioles and capillaries. CONCLUSIONS: Structure of outer myometrial uterine leiomyomata was similar to those observed during growth within myometrium.

Vascular architecture of the human uterine cervix, as assessed in light- and scanning electron microscopy.

BACKGROUND: The aim of this study was to visualise and describe the vasculature of the human uterine cervix. MATERIAL AND METHODS: The material for this study was obtained from women (age between 20 to 45 years) during autopsy. The material was collected not later than 24 h post-mortem. This study was performed using uteri from cadavers of menstruating nulliparas (33 uteri) and menstruating multiparas (27 uteri). Collected uteri were perfused via the afferent vessels with Mercox resin (for corrosion-casting and SEM assessment) or acrylic paint solution (light microscopy assessment). The research protocol was approved by the Jagiellonian University Ethics Committee (registry KBET/121/8/2007). RESULTS: In all cases bilateral cervical branches (1-4), originating from the uterine artery, were found. Both in the vaginal and supravaginal parts of the cervix, four distinct vascular zones were found. In the pericanalar zone ran small veins, responsible for draining the mucosal capillaries. Both in the muscular layer, as well as in the pericanalar zone, arterioles, and venules passed close to each other, often adjoining. CONCLUSIONS: This study does not confirm the existence of a single cervicovaginal artery, but shows that the vascular supply of the cervix comes from several vessels. It also introduces the idea of two systems, responsible for draining blood from the mucosal capillaries. Neither assessment in light microscopy nor in SEM revealed any differences between multiparas and nulliparas, regarding the vascular architecture of the cervix.

Uterine fibroid pseudocapsule studied by transmission electron microscopy.

OBJECTIVE: The fibroid pseudocapsule is a structure which surrounds the uterine fibroid, separates it from the uterine tissue and contains a vascular network rich in neurotransmitters like a neurovascular bundle. The authors examined the composition of the fibroid pseudocapsule using electron microscopy. STUDY DESIGN: Twenty non-pregnant patients were submitted to laparoscopic myomectomy by the intracapsular method and samples of the removed pseudocapsules were analyzed using transmission electron microscopy. RESULTS: At the ultrastructural level the pseudocapsule cells have the features of smooth muscle cells similar to the myometrium. So, the pseudocapsules are part of the myometrium which compresses the leiomyoma. CONCLUSION: This ultrastructural feature suggests that when removing fibroids their pseudocapsules should be preserved. This study confirms preliminary evidence that pseudocapsules contain neuropeptides together with their related fibers, as a neurovascular bundle. The surgeon's behavior should be directed to carefully control and spare this muscular surrounding tissue during fibroid excision, in order to preserve the myometrium as much as possible.

Intramyometrial uterine cysts with special reference to ultrastructural findings: report of two cases.

An intramyometrial cyst is an extremely rare condition that is characterized by a benign, endometrial, epithelium-lined cyst within the thickened myometrium. Few cases of intramyometrial cysts have currently been reported in the literature, with or without microscopic description. We have experienced two cases of intramyometrial cysts. One was a 6.5 cm-sized cyst and the other was a 3.0 cm-sized cyst accompanied by adenomyosis. Case 1 was a 41-year-old female and case 2 was a 51-year-old female who had been suffering from menorrhagia for several days. A total hysterectomy was performed for both women. Histological examination showed that the huge cysts were composed of single-layered, ciliated, cuboidal epithelia surrounded by diffusely thickened myometrium. Ultrastructural examination of case 1 showed the lining cells of the cyst consisted of the basalis-type endometrial epithelial cells that have surface microvilli. The cells were surrounded by a duplicated basal lamina and joined by well-formed desmosomes. We report here on two cases of intramyometrial cyst with special reference to the ultrastructural examination, and we discuss the pathogenesis of this rare lesion.

[Relationship between ultrastructural features with the expression of connexin 43 in the uterine junction zone and pathogenesis of adenomyosis].

OBJECTIVE: to investigate the relationship between the ultrastructural features combined with the expression of connexin (Cx43) protein in uterine junction zone and pathogenesis of adenomyosis. METHODS: from Nov. 2008 to Nov. 2009, 30 patients with adenomyosis (including 14 cases with proliferative endometrium and 16 cases with secretory endometrium) as study group matched with 30 women with cervical intraepithelial neoplasia (CIN) III treated by hysterectomy as control group were enrolled in this study in Affiliated Hospital to Inner Mongolia Medical College. The expression of Cx43 in uterine junction zone of patients with adenomyosis was detected by immunohistochemisty staining. The ultrastucture of eutopic endometrium, uterine junction zone and outer 1/3 myometrium in both groups without history of dilatation and curettage, C-section and uterine surgery were observed by using transmission electron microscopy. RESULTS: (1) the expression of Cx43 in proliferative and secretroy uterine junction zone were 0.133 ± 0.018 and 0.137 ± 0.021 in study group and 0.154 ± 0.016 and 0.141 ± 0.018 in control group, which reached statistical difference (P < 0.05). However, it didn't show significant expression of Cx43 between proliferative and secretory uterine junction zone in study or control group (P > 0.05). The expression of Cx43 in proliferative and secretory of eutopic endometrium of 0.067 ± 0.017 and 0.062 ± 0142 in study group were significantly lower than 0.094 ± 0.005 and 0.080 ± 0.005 in control group. It didn't show statistical difference of Cx43 expression between proliferative and secretroy eutopic endometrium in both group. The expression Cx43 in outer myometrium of proliferative phase were 0.184 ± 0.022 in study group and 0.188 ± 0.028 in control group, which did not show significant difference (P > 0.05). It also did not exhibit statistical difference of Cx43 expression in outer myometrium of secretory phase (0.178 ± 0.022, 0.191 ± 0.025, P > 0.05). (2) Morphological changes: the area of uterine smooth muscle cells of the uterine junction zone of (24.3 ± 1.6) microm(2) in study group were significantly increased than (21.8 ± 2.0) microm(2) in control group (P < 0.01). The length of the cell membrane dense plaques of (1.07 ± 0.17) microm in study group was significantly increased than (0.71 ± 0.07) microm in control group (P < 0.01). The myocytes exhibited cellular hypertrophy and disordered arrangement and fewer caveolae. There was cylindrical and dentate, chromatin margination, more heterochromatin in which muscle cells of nuclear surface of the uterine junction zone. Less cytoplasmic myofilaments and more intermediate filaments. Mitochondria were increased, the volume increased significantly vacuolization. The rough endoplasmic reticulum and Golgi apparatus were more prominent. Otherewise, mast cells and fibroblasts were close and glandular epithelial cells showed desmosome connection which villus thickening and dense. All features were more prominent at the junctional zone. CONCLUSIONS: the down-regulation of Cx43 expression and ultrastructure changes in the junction zone might play an important role in pathogenesis of adenomyosis.

Uterine adenomyosis is associated with ultrastructural features of altered contractility in the inner myometrium.

OBJECTIVE: To study the ultrastructure of the inner and outer myometrium, in the presence and absence of uterine adenomyosis. DESIGN: Case control blinded comparison. SETTING: University departments. PATIENT(S): Four premenopausal women with and six without uterine adenomyosis as the sole pathology. INTERVENTION(S): Multiple samples were studied using transmission electron microscopy. MAIN OUTCOME MEASURE(S): Ultrastructure feature of the myometrium. RESULT(S): In uteri with adenomyosis, the myocytes exhibited cellular hypertrophy. The cytoplasmic myofilaments were less abundant. Abundant intermediate filaments formed cytoplasmic aggregates. The nuclei had a smooth outline with a clear ground substance, prominent nucleoli and peripherally arranged nuclear chromatin. There was occasional infolding of the nuclear envelope with entrapment of cytoplasmic organelles. The sarcolemmal bands were significantly longer and there were fewer caveolae. The perinuclear cell organelles were more distinct. The rough endoplasmic reticulum and Golgi apparatus were more prominent, denoting active protein synthesis, consistent with the observed cellular hypertrophy. All features were more prominent at the junctional zone. CONCLUSION(S): Smooth muscle cells from uteri with adenomyosis are ultrastructurally different from smooth muscle cells of normal uteri. These distinct features suggest a possible effect on myometrial contractility, together with hypertrophy.