Mateusz Mikołajczyk

Oxidative stress may be a piece in the endometriosis puzzle

OBJECTIVE To assess the total antioxidant potential of women with endometriosis-associated infertility, women with idiopathic infertility, and fertile controls. DESIGN Retrospective study. SETTING University medical hospital. PATIENT(S) Sixty-five women admitted for diagnostic laparoscopy. MAIN OUTCOME MEASURES Peritoneal fluid samples were analyzed for superoxide dismutase activity and total antioxidant status on spectrophotometry, glutathione peroxidase activity on enzyme-linked immunosorbent assay, and lipid peroxides levels on colorimetry. RESULT(S) Mean activity of superoxide dismutase, glutathione peroxidase, and total antioxidant status was lowest and lipid peroxide level was highest among infertile patients with endometriosis. Women with idiopathic infertility, in contrast, had the highest superoxide dismutase, glutathione peroxidase, and total antioxidant status activity and the lowest lipid peroxide level. CONCLUSION(S) High antioxidant potential is not a contributing factor in women with idiopathic infertility. Low total antioxidant status and low activity of antioxidant enzymes in the peritoneal fluid of infertile women with endometriosis probably do not influence fertility in these women, but these factors may play a role in the development of the disease.

The Impact of Leukemia Inhibitory Factor in Uterine Flushing on the Reproductive Potential of Infertile Women – A Prospective Study

To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome.

Could the Defects in the Endometrial Extracellular Matrix During the Implantation Be a Cause for Impaired fertility

Assessment of concentration of the metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinases 1 (TIMP1), urokinase plasminogen activator (uPA) and its receptor (uPAR) and leukaemia inhibitory factor (LIF) in the uterine fluid in women with idiopathic infertility and unknown cause for recurrent miscarriage.

No correlation between pinopode formation and LIF and MMP2 expression in endometrium during implantation window.

Implantation depends on two factors - embryo and endometrium. The period of maximal endometrial receptivity is a poorly understood phenomenon. We decided to look at three possible markers of implantation: pinopodes, leukemia inhibitory factor, and matrix metalloproteinase 2 and their correlations. We included in the study 23 idiopathic infertility patients and 21 patients with recurrent spontaneous abortions of unknown etiology. Twenty one fertile patients were also recruited. A biopsy was used for endometrial dating according to the Noyes and Hertig criteria, and assessed for the presence of pinopodes via a scanning electron microscope. Endometria were examined in Real Time-Polymerase Chain Reaction cycles for the mRNA expression of leukemia inhibitory factor (LIF) and matrix metalloproteinase 2 (MMP2). No difference was found in the stage of pinopodes development, nor in the coverage of endometrial surface between the studied groups. The expression level for LIF mRNA was lower in control patients compared to idiopathic infertility and recurrent miscarriage patients. No difference was detected in the expression of MMP2 between all studied groups. No correlation was found between pinopodes development stage and LIF and MMP2 expressions in endometrium. Of the studied factors, LIF and pinopodes show the most promise as potential markers of endometrial receptivity. However, the results achieved suggest that these markers are independent of each other.

Assessment of the transcription levels for the complement activation control system in eutopic endometrium in women with two or more consecutive miscarriages of unknown etiology

Human endometrium, deciuda and placenta have been shown to express factors that inhibit the complement activation cascade - decay-accelerating factor (DAF), membrane cofactor protein (MCP) and the C3 complement component. In the following study we have analyzed the transcripts levels for DAF, MCP and heparin-binding epidermal growth factor-like growth factor (HB-EGF), the C3 complement component and receptor for vascular endothelial growth factor (VEGFR1) as markers of endometrial unbalance between factors activating the complement system in women with consecutive miscarriages. Study enrolled 30 women with at least two consecutive miscarriages, and 19 healthly women, that comprised the control group. RNA was isolated from endometrial samples. Transcripts levels of DAF and MCP was higher in women with consecutive miscarriages compared to controls, 0.78 vs 5.08 (p<0.001) and 0.25 vs 0.17 (p=0.001) respectively. In consecutive miscarriages group, DAF and MCP expression was correlated with the C3 expression, with r=0.60; p<0.001 and r= 0.40; p=0.03 respectively. Correlation between DAF and C3 was also noted in controls, 0.70; p=0.001. In women with two or more consecutive miscarriages the analysis proved higher expression of genes that encode proteins that inhibit the complement cascade. Further studies are needed to confirm that this might be a reaction to increased presence of the complement factors, which like C3 that are synthesized in the endometrium.

Correlation of the expression of heparanase and heparin-binding EGF-like growth factor in the implantation window of nonconceptual cycle endometrium

Although it was suggested that heparanase (HPSE) may affect implantation and pregnancy, so far there have been no wide-ranging studies on the expression of and possible disturbances in the interactions between HPSE, heparan sulfate (HS) and related growth factors, such as heparin-binding EGF-like growth factor (HB-EGF). The aim of this study was to evaluate whether the expression profile of both HPSE and HB-EGF can be associated with impaired reproduction in the endometrial implantation window, in the non-conception cycle. The study group consisted of 32 women with two or more unexplained, consecutive miscarriages, and 61 idiopathic infertility patients, while the control comprised of 22 women with normal reproductive potential. We compared the expression of HB-EGF and HPSE at the transcript (qPCR) and protein (Western Blot) levels in eutopic endometrium. Also assessed were correlations between both factors in the studied groups. In women with consecutive miscarriages we observed lower HPSE relative transcript (p = 0.003) and lower protein (p = 0.002) level compared with the control group. Level of the HB-EGF protein was decreased (p = 0.017). HPSE mRNA level was higher in idiopathic infertility (p = 0.003) compared with women with miscarriages. We found statistically significant correlations in both transcript and protein levels in all groups (p < 0.05). Our results allow the assumption of the existence of a process by which, in normal human endometrium, HB-EGF expression coincides with the synthesis of HPSE. As a result, the HB-EGF molecule can bind to the HS on the cell surface, enhancing its affinity to the receptor. Then, the release of growth factors associated with HS oligomers occurs that is catalyzed by HPSE. We suggest that one of the causes of unexplained miscarriages may result from the impaired expression of HPSE and HB-EGF.

In Vivo Correlation between IL-1β Concentration in Uterine Fluid and Integrin Expression Pattern in Infertile Women

Problem  To evaluate the possible correlation between interleukin‐1beta (IL‐1β) and integrin expression.

Matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinases (TIMP-1) and transforming growth factor-β2 (TGF-β2) expression in eutopic endometrium of women with peritoneal endometriosis

INTRODUCTION The prevalence of endometriosis among reproductive age women is 7-17%; however, these figures reach 20-50% in patients suffering from infertility. Matrix metalloproteinases (MMPs) activity is thought to be particularly essential in the early phases of endometriosis development. Any changes in the equilibrium between MMPs activity and their tissue inhibitors (TIMPs) could be potentially harmful, promoting endometriosis development. The aim of this study was to investigate whether the MMP-2, MMP-9, TIMP-1 or TGF-B2 expression in eutopic endometrium from women with early endometriosis differ when compared with healthy subjects. The results were referred to the serum progesterone levels. MATERIALS AND METHOD Endometrial biopsy was taken from 42 patients (18 in the study group, 22 in thecontrol group) at the time of hysteroscopy for routine histology and for RT-PCR procedures. Comparison of the quantity of gene products was performed with a programme for densitometry and compared to GADPH product, which was a reference value. RESULTS The obtained results did not reveal any statistical difference in endometrial expression of MMP-2, MMp-9, TIMP-1, and TGF-β2 or serum progesterone level between women with endometriosis and without visible signs of this illness. CONCLUSION Despite the lack of statistical differences, it was observed that both examined metalloproteinases expressed a tendency to higher gene expression in the eutopic endometrium of women with endometriosis. However, both TIMP-1 and TGF-β2 expressions had the same tendency - higher values in endometriosis patients.

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis

OBJECTIVES The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. MATERIAL AND METHODS Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. RESULTS In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. CONCLUSIONS Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

The course and delivery of a pregnancy in a patient with autoimmune hepatitis complicated by cirrhosis of the liver

Małgorzata Szczepańska1, Nikodem Horst2, Mateusz Mikołajczyk1, Tomasz Banasiewicz3, Ewa Wender-Ożegowska1 1Division of Reproduction, Department of Obstetrics, Gynaecology and Gynaecological Oncology, Poznan University of Medical Sciences, Poznan, Poland 2Department of General and Colorectal Surgery, Poznan University of Medical Sciences, Poland 3Department of General Surgery, Gastroenterological Oncology Surgery and Plastic Surgery, Poznan University of Medical Sciences, Poland