Effectiveness of myo-inositol oxygenase in the early diagnosis of experimental acute kidney injury.

OBJECTIVES: The effectiveness of the myo-inositol oxygenase (MIOX) enzyme was investigated in the diagnosis of acute kidney injury (AKI). METHODS: In total, 40 rats were divided into 5 groups (n = 8, for each group) while left kidney ischemia-reperfusion was implemented in groups 2, 3, 4 and 5. Group 1 was the control group. Group 2 underwent 1­hour ischemia and 2­hour reperfusion. Group 3 underwent 1­hour ischemia and 4­hour reperfusion. Group 4 underwent 2­hour ischemia and 2­hour reperfusion. Group 5 underwent 2­hour ischemia and 4­hour reperfusion. RESULTS: Serum creatinine and blood urea nitrogen levels in all ischemia-reperfusion groups were higher than in the control group (p<0.001). Serum MIOX level was higher in groups 2, 3 and 4 than in group 1 (p=0.002). Tissue MIOX level was lower in groups 2, 4, and 5 than in group 1 (p=0.039). Serum and tissue neutrophil gelatinase-associated lipocalin levels were not significantly different between the groups. The injury level in histopathologic examination was as follows: group 1

Harmful effects of formaldehyde and possible protective effect of Nigella sativa on the trachea of rats.

OBJECTIVE: We aimed in this study to investigate the harmful effects of formaldehyde (FA) inhalation and possible protective effects of Nigella sativa (NS) on rats' trachea. MATERIALS AND METHODS: In this study, 63 adult male rats were used. Animals were divided into nine groups. Group I was used as control group. All other groups were exposed to FA inhalation. Group III, V, VII, and IX were administered NS by gavage. Tissues were examined histologically, and immunohistochemical examination for Bax and caspase-3 immunoreactivity was carried out. RESULTS: Our study demonstrated that FA caused apoptosis in the tracheal epithelial cells. The most apoptotic activity occurred at a 10 ppm dose in a 13-week exposure. Distortion of tracheal epithelium and cilia loss on epithelial surface was present in all groups. However, NS treated Groups VII and IX had decreased apoptotic activity and lymphoid infiltration and protected the epithelial structure, despite some shedded areas. Difference of tracheal epithelial thickness and histological score was statistically significant between Group VI-VII and VIII-IX. CONCLUSION: FA induces apoptosis and tracheal epithelial damage in rats, and chronic administration of NS can be used to prevent FA-induced apoptosis and epithelial damage.

Tracheobroncopathia osteochondroplastica: Three case reports with literature review.

Tracheobroncopathia osteochondroplastica (TO) is a benign disease of the large airways seen very rarely. It is characterized by 1-3 mm sized ossified nodular lesions in submucosa. Its etiology is unclear, but it is stated that malignancy, chronic inflammation, amyloidosis, and genetic factors might have an effect on it. It was first described by Wilks in a 38-year-old man diagnosed with tuberculosis in 1857. Generally, patients are asymptomatic and TO is diagnosed incidentally. But symptoms become significant with infections and obstruction in tracheabronchial tree. Generally chest radiography is normal, so thorax computed tomography can be remarkable in diagnosis of TO. Besides, final diagnosis can be established by viewing ossified nodules in trachea and bronchus through the fiberoptic bronchoscopy. Amyloidosis, tuberculosis, sarcoidosis, bronchial carcinoma, and tracheobronchial calcinosis must be remembered in differential diagnosis. Also ossifications in submucosa and proof of bone marrow in histopathological examinations are important in diagnosis of TO. Mostly palliative treatment is performed to the symptoms . We want the clinicians to keep in mind for this very rarely seen tracheal disease with three case reports.

HGF/C-MET PATHWAY HAS A ROLE IN TESTICULAR DAMAGE IN DIABETES INDUCED BY STREPTOZOTOCIN.

OBJECTIVE: The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)- induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway. METHODS: Total 21 paraffin-embedded testicular tissues of control (n=7), streptozotocin (STZ)-induced diabetic (n=7) and insulin-treated diabetic (n=7) Wistar albino rats were used in this study. Testicular damage was examined histologically and by Johnsen's score was also evaluated. Immunohistochemical stainings of HGF and c-Met were analysed by using antibodies against HGF and c-Met. RESULTS: We found the degeneration in seminiferous tubule epithelium and disorganization of spermatogenetic cell series in testis tissues of diabetic rats. We also determined decrease both in seminiferous tubule diameter and Johnsen's scores in diabetic group. The expressions of HGF and c-Met in seminiferous tubule epithelium and in spermatogenic cells (especially spermatocytes and spermatids) were significantly increased in diabetic rats compared to those of control. Insulin treatment significantly reduced the diabetes-induced morphological changes and HGF/c-Met over expressions in the diabetic rat testis. CONCLUSION: HGF/c-Met pathway might have a role in diabetes- induced testicular damage. Drugs acting on this pathway might be effective to prevent or delay the testicular damage induced by diabetes.

Central nervous system toxicity after acute oral formaldehyde exposure in rabbits: An experimental study.

Formaldehyde (FA) is one of the most widely used chemical compounds in industrial field. It is described as toxic, particularly to the nervous system, the urogenital system, and the respiratory tracts. In this study, we determined the effects of acute oral exposure to FA in rabbit brain tissue. A total of 16 rabbits were selected and divided into 2 groups: formaldehyde group (group F) and control group (group C). FA was administered to group F at a rate of 40 mg/kg/day via a nasogastric tube for 5 days. Saline was similarly administered to the eight controls. All the animals were euthanized after 5 days of exposure, and brain tissue samples were collected in 10% neutral formalin and embedded in paraffin. To investigate the effects of FA on the apoptotic process, we examined active caspase-3, Bax, and Bcl-2 immunohistochemical expression and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate -biotin nick-end labeling (TUNEL) reactivity in the rabbit brains. In addition, glial fibrillary acidic protein (GFAP) was biochemically assessed in brain tissue samples for neurotoxicity. We found that FA treatment caused a significant decrease in Bcl-2 expression and an increase in active caspase-3 and Bax expressions as well as an increase in the number of TUNEL-positive apoptotic cells. The GFAP level was found to be significantly higher in group F. In conclusion, acute oral exposure to FA caused DNA damage, apoptosis, and neuronal injury in the rabbit brains.

Immunohistochemical detection of p53 and MDM2 expressions in liposarcoma with World health organization classification.

BACKGROUND: Liposarcomas are among the most common soft tissue sarcomas in adulthood. AIM: The purpose of the study is to perform a histopathologic typing according to World Health Organization (WHO) classification of cases diagnosed with liposarcoma and to examine the difference of p53 and MDM2 expressions. MATERIALS AND METHODS: The haematoxylin-eosin stained sections of 48 subjects enrolled in the study have been evaluated on the basis of the WHO classification for liposarcoma and sections stained using p53 and MDM2. STATISTICAL ANALYSIS USED: Chi-Square test was applied. RESULTS: 20 subjects were diagnosed with well-differentiated liposarcoma (WLS), 16 myxoid liposarcoma (ML), 7 pleomorphic liposarcoma (PL), and 5 de-differentiated liposarcoma (DLS). The number of cases stained positive with MDM2 and p53 were positive correlated in all subjects (P = 0.02). p53 and MDM2 positivity increased in high grade tumors (P = 0.01). CONCLUSION: p53 and MDM2 immuno-reactivity was found to be potentially useful in liposarcoma diagnosis but a definitive implication would be rather unhealthy due to the small number of cases in our study.

Effects of isoflurane in an intoxication model: experimental study.

BACKGROUND: Isoflurane is a volatile anaesthetic that has been commonly used since 1980. The major metabolites of isoflurane are fluoride ion and trifluoroacetate, both excreted in the urine. AIM: This study manage to show the histopathological findings of ingested isoflurane on liver, kidney and lugs in an animal model. Twenty-one rabbits were selected and divided into three groups: Group Isoflurane-5 (I-5); Group Isoflurane-10 (I-10); and Group Control (C). Each group consisted of seven rabbits. I-5 and I-10 received 5 ml/kg and 10 ml/kg of liquid isoflurane, respectively, via nasogastric tube, while C received 5 ml/kg saline (0.9% NaCI). All animals in I-5 and I-10 were sacrificed without anesthetic drug administration. Tissue samples from livers, kidneys and lungs were collected, preserving tissue unity and avoiding infliction of any trauma. Samples were fixed in 10% formalin solution, embedded in paraffin blocks and sliced into 5 µm sections. To investigate the effects of isoflurane, sections were examined under light microscope and histopathological changes were scored. RESULTS: Mean injury scores and the appearance of portal lymphocyte infiltration in liver samples showed significant increases in I-5 and I-10 compared to C (p = 0.005, p = 0.001 and p = 0.001, respectively). Mean lung injury scores revealed significant increases after isoflurane treatment in I-5 and I-10 compared to C (p = 0.026 and p = 0.017, respectively). CONCLUSIONS: Ingested isoflurane led to mild liver and lung injuries in rabbits.

High rate of allergies among women with endometriosis.

Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.

Effect of the new legislation and single-embryo transfer policy in Turkey on assisted reproduction outcomes: preliminary results.

New legislation concerning assisted reproduction treatments was introduced in Turkey in March 2010 in order to reduce the number of multiple pregnancies. This new legislation limits the number of embryos to be transferred to one under 35 years of age in the first or second treatment cycles and to two in the third or further cycles or for 35 and older ages. The aim of this multicentre study was to investigate the effect of this new law on clinical pregnancy and multiple pregnancy rates. Outcomes were compared in equal periods of 2.5 months before and after the new law, and further investigation was conducted for two different age groups: <35 and ≥ 35. The clinical pregnancy rates decreased from 39.9 to 34.5% and multiple pregnancy rates decreased from 23.1 to 5.3% (P<0.001) for the overall population. The outcomes of the <35 age group and ≥ 35 age group were also similar to that of the overall population. These results suggest that under the new legislation multiple pregnancy rates are significantly reduced without causing a significant decline in the pregnancy rates.

Endometriosis-associated Lyme disease.

The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.

Association of endometriosis with family history of non-Hodgkin's lymphoma: presentation of 10 cases.

PURPOSE: Women with endometriosis have been reported to be at increased risk of developing non-Hodgkin's lymphoma (NHL). The purpose of this article was to investigate the familial risk of NHL in women with endometriosis. We report on 10 cases with endometriosis and positive family history of NHL. METHODS: The medical records of 405 women with endometriosis and 200 without endometriosis were retrospectively analysed. All of the cases were diagnosed by laparoscopy. Ten cases of endometriosis having first-degree relatives with NHL are reported. RESULTS: We found no case with endometriosis and NHL. In contrast, we found 10/405 (2.5%) women with endometriosis and first-degree relatives with NHL. Their mean age was 38.3 years (range 29-46). The main complaint was infertility. The mean age at onset of endometriosis was 32 years (range 22-43). The stages of endometriosis were: stage II (n=4), stage III (n=2) and stage IV (n=4). All of these patients had first-degree relatives with a history of NHL. Five had mothers with NHL, 5 had fathers and one had a sister. CONCLUSION: These cases could suggest a link between a family history of NHL and subsequent development of endometriosis in the first-generation women. Moreover, there was no evidence of association between endometriosis and NHL.

Regulation and activation of ezrin protein in endometriosis.

BACKGROUND: Ezrin protein and its activated form phospho-ezrin play a role in cell morphology, motility and adhesiveness. In this study, we hypothesized that these proteins play a role in the pathogenesis of endometriosis by promoting adhesion and invasion of endometrial stromal cells (ESCs) in ectopic sites. METHODS: We compared the expression of ezrin and phospho-ezrin in normal endometrium from women without endometriosis with their expression in eutopic and ectopic endometrial tissues from women with endometriosis, using immunohistochemistry and western blot analysis. Paired eutopic and ectopic endometrial tissue samples from women with endometriosis (n = 13) and normal endometrium from women without endometriosis (n = 12) were collected. Invasive potential of ESCs from each of these samples was compared using Matrigel membrane invasion assay. RESULTS: Eutopic and ectopic endometrial tissues from women with endometriosis have higher ezrin and phospho-ezrin levels as confirmed by immunohistochemistry and western blot analysis (P < 0.05). The Matrigel membrane invasion assay revealed that ectopic ESCs have more invasive characteristics, more protrusions and higher ezrin staining than normal ESCs (P < 0.05). CONCLUSIONS: Ezrin can be a potential marker for endometrial cell invasion and may play a role in the pathogenesis of endometriosis.

Epidemiological factors influencing IVF outcome: Evidence from the Yale IVF program.

Age, BMI, lifestyle, menstrual status and obstetric history can modulate the endocrine system and, therefore, have been hypothesised to play a role in in-vitro fertilisation (IVF) outcome. We designed a retrospective study, set in a medical school hospital. We evaluated the medical files of 297 infertile women who underwent laparoscopy and consecutive IVF-ET treatment in the Yale IVF unit between 1996 and 2002. The study group consisted of 151 women who conceived after IVF-ET and the control group of 146 women who underwent 288 IVF-ET cycles without pregnancy. The main outcome measure was the impact of epidemiological factors on the IVF outcome. There was no association between IVF outcome and race, BMI, age at menarche, length of cycle, duration and amount of flow, menstrual symptoms, other medical problems, medical history of allergies, and family history of endometriosis and cancer. We found that the degree of smoking and alcohol use was not a factor when comparing women with and without pregnancy after IVF (34.5% vs 29.5%, and 33.7% vs 27%, respectively). The rate of duration of infertility tended to be lower in pregnant women (35.9+/-23.4 months) vs (42.3+/-30.2) non-pregnant women. As expected, we also confirmed the inverse association between the age of women and IVF outcome. Overall, body attributes, lifestyle, family history, menstrual and reproductive factors were not related to IVF-ET outcome.

Cycle outcome can be predicted by the growth profile of untransferred cleavage-stage embryos.

Excess embryos obtained from intracytoplasmic sperm injection cycles may be cultured and observed until day 5 if the couple receiving treatment do not want them to be cryopreserved. In order to investigate the correlation between blastocyst formation in extended culture and pregnancy outcome, 194 patients treated in two separate IVF units were examined retrospectively. The patients were separated into two groups: group 1 with at least one blastocyst formed in culture, and group 2 with no blastocyst formation. The pregnancy rates were 60.0% and 41.7% for groups 1 and 2, respectively. The pregnancy rate in group 1 was statistically significantly higher than in group 2 (P = 0.01). The results suggest that the developmental potential of embryos obtained from a single assisted reproduction treatment cycle may be similar and that blastocyst formation in vitro may help to predict the pregnancy outcome of that cycle.

Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis.

BACKGROUND: Women with endometriosis who are treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate compared to women with tubal factor infertility. It has been suggested that the administration of gonadotrophin releasing hormone (GnRH) agonists for a few months prior to IVF or ICSI increases the pregnancy rate. OBJECTIVES: To determine the effectiveness of administering GnRH agonists for three to six months prior to IVF or ICSI in women with endometriosis. SEARCH STRATEGY: We used computer searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG Specialised Register of controlled trials. We handsearched proceedings of annual meetings of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists of references in original research and review articles. We contacted experts in various countries to identify unpublished trials. SELECTION CRITERIA: We included randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat women with any degree of endometriosis diagnosed by laparoscopy or laparotomy DATA COLLECTION AND ANALYSIS: Two independent review authors abstracted data (HNS and JGV). We sent e-mails to investigators to seek additional information. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. The data were checked by the third review author (SD) and any disagreement was resolved by arbitration with the fourth review author (AA). We generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel-Haenszel technique was used to calculate odds ratios (OR) and assess statistical heterogeneity between studies. MAIN RESULTS: Three randomised controlled trials (with 165 women) were included. The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting "viable pregnancy" only. The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The information on miscarriage rates came from two trials with high heterogeneity and, therefore, results of the meta-analysis were doubtful. The included studies provided insufficient data to investigate the effects of administration of GnRH agonists on multiple or ectopic pregnancies, fetal abnormalities or other complications. AUTHORS' CONCLUSIONS: The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

Immunology of endometriosis.

Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease. There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis. Increased number and activation of peritoneal macrophages, decreased T cell and natural killer (NK) cell cytotoxicities are the alterations in cellular immunity and result in inadequate removal of ectopic endometrial cells from the peritoneal cavity. Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis. In addition to the impaired capacity of the immune cells to mediate endometrial cell removal, inherent resistance of the ectopic endometrial cells against immune cells is another interesting concept in the pathogenesis of endometriosis. Endometriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.

Regulation of Fas ligand expression by vascular endothelial growth factor in endometrial stromal cells in vitro.

When Fas ligand (FasL) interacts with the Fas receptor, it induces apoptosis through autocrine and/or paracrine signalling. Vascular endothelial growth factor (VEGF) is a potent mitogenic cytokine. VEGF plays a role during remodelling of the endometrium following menstruation. We hypothesized that, by regulating FasL expression, VEGF may play a role in endometrial stromal cell survival by decreasing autocrine apoptotic signalling. We aimed to determine the expression of FasL in cultured endometrial stromal cells and its modulation by VEGF. VEGF induced a decrease in both FasL-positive cell number and FasL intensity as determined by immunocytochemistry and western blot respectively (P < 0.05). These effects of VEGF were observed in a concentration-dependent manner (10-42%; P < 0.05). Anti-VEGF neutralizing antibody alone resulted in an increase in the FasL expression. When combined with VEGF, anti-VEGF reversed the VEGF-induced decrease in FasL level up to 100% (P < 0.05). In addition, western blot analysis showed that FasL expression in endometrial stromal cells demonstrated a cyclic change every 12 h during 48 h of incubation. These results suggest that down-regulation of FasL by VEGF may affect endometrial stromal cell survival in an autocrine or paracrine manner. The decrease in FasL level may be due to a stimulation of its degradation. Our results show that FasL in endometrial stromal cells in culture has a cyclic expression model, suggesting that there may be a regulation at the translation level.

Endocrine-immune interactions in human endometrium.

The immune system is a complex entity designed to eliminate foreign intruding antigens and is influenced by and, in turn, influences the function of the reproductive system. Despite the widespread associations between immunology and reproductive medicine, the study of system interactions remains in its infancy. Many diverse facts are accumulating, and pieces of the puzzle are becoming available to provide a clearer picture. In this review article, we focus on the interactions between endocrine and immune systems in the human endometrium. Understanding the molecular pathways in endocrine-immune interactions in the human endometrium is crucial to understand events such as menstrual bleeding, tissue repair and regeneration, inflammation, angiogenesis, blastocyst implantation, and progression of pregnancy. These events require a balanced regulation of endometrial differentiation, proliferation, cell survival, leukocyte recruitment, apoptosis, and angiogenesis by sex steroids. In this review, we first outline the role of survival factors such as phosphoinositol 3-kinase/protein kinase B, PTEN, NFkappaB, and apoptotic molecules (Fas-FasL, Bcl-2). We then discuss their regulation by estrogen and progesterone in the endometrium. We present evidence for direct and/or indirect roles of steroid hormones on the expression of chemotactic cytokines (interleukin-8 and monocyte chemotactic protein-1) and on the survival versus apoptosis of resident endometrial cells (stromal, epithelial, and endothelial cells) and nonresident cells (leukocytes).

The effect of oral versus vaginal misoprostol on cervical dilatation in first-trimester abortion: a double-blind, randomized study.

OBJECTIVES: To determine the effect of oral versus vaginal misoprostol on cervical dilatation in first-trimester intrauterine evacuation or menstrual regulation (MR). DESIGN AND METHODS: A total of 120 patients were randomly assigned to a double-blind prestudy. Four groups, each consisting of 30 cases, were administered one of four regimens: 200 microg misoprostol orally, 200 microg misoprostol intravaginally, placebo orally, or placebo intravaginally, 10 h before MR, respectively. Age, number of births and abortions, birth methods, date of last delivery and last abortion were recorded. The gestational age was determined by ultrasonography. Prior to MR, data regarding the time of the application of the drug, the presence of placenta in the cervical canal, the degree of cervical dilatation, the duration of MR and patients' complaints were recorded. The MRs were performed by the same physician. The statistical analyses were evaluated with the chi(2) test and Fisher's exact test in the Aegean University Science Faculty Department of Statistics. RESULTS: In the oral misoprostol group, four patients had cervical bleeding and one had intracervical placenta. In the intravaginal misoprostol group, cervical bleeding was observed in seven patients and intracervical placenta was recorded in four cases. Cervical bleeding was observed in one case and intracervical placenta was also observed in one case in the oral placebo group. Cervical dilatation reached 8 mm in seven patients in the oral misoprostol group and in three patients in the intravaginal group, with none in the placebo group. Symptoms such as pelvic pain, headache and nausea were observed in 11 cases in the oral and 14 cases in the vaginal misoprostol groups. CONCLUSIONS: Different methods of misoprostol administration may not be equivalent in terms of efficacy and side-effects. Therefore, we decided to extend the study to include more patients so as to achieve statistically significant results.

Structural differentiation of human uterine luminal and glandular epithelium during early pregnancy: an ultrastructural and immunohistochemical study.

The differentiation of human endometrial epithelium is a dynamic event that occurs throughout the menstrual cycle and early pregnancy. The structural transformation and differentiation of human uterine luminal and glandular epithelium of early human pregnancy (n=14) was investigated ultrastructurally and immunohistochemically using antibodies against cytokeratin (CT), endothelial marker CD31, Fas, and proliferating cell nuclear antigen (PCNA). Ultrastructurally, luminal epithelial cells showed distinctive euchromatic nuclei with prominent nucleoli and relatively loose cell membranes in all poles (apical to basal). Subcellular components were easily recognized in luminal epithelium except in degenerating cells. Mainly two cell types, dark and clear cells, formed the glandular epithelium. In the early gestation period, microvilli were abundant on the apical and apico-lateral poles of these cells. Only a few cytoplasmic projections were observed in dark cells. Numerous cilia were observed on the apical pole of some clear cells, located at the adluminal segment. In contrast, dark cells lacked cilia, nuclear channels, or giant mitochondrial profiles. Glycogen synthesis and apocrine secretion were recognizable for several days during early gestation. The apocrine secretory activity differed among dark cells of the glandular epithelium. The immunoreactivity of PCNA and Fas, and ultrastructural observations in the glandular epithelium suggest that, even in different segments of the same gland, epithelial cells do not regress during early gestation, but proliferate, perhaps representing a resistance against trophoblastic invasion. These morphological and molecular changes suggest that both luminal and glandular epithelium may play an important role in cellular defense and limitation for trophoblastic invasion during early pregnancy since plasma membrane alterations of the surface epithelium take place at the apical, basal and lateral poles compared to early secretory phase endometrial cells. Besides glandular epithelium may be consequently responsible for uterine secretions, which may be critical for early embryo development.