Long pentraxin 3 and vitamin D receptor mRNA expression pattern of cumulus granulosa cells isolated from PCOS oocytes at different stages of nuclear maturation.

BACKGROUND: A fine-tuned pro-inflammatory and anti-inflammatory balance in the follicular unit is essential for cumulus expansion and successful ovulation. While the long pentraxin 3 (PTX3) gene is required for the expansion of cumulus cells (CCs), ovulation, resumption of meiosis and fertilization, the vitamin D receptor gene (VDR-X2) is required for intra-follicle redox balance. This study was planned to determine the expression pattern of VDR-X2 and PTX3 mRNA in CCs isolated from germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) oocytes of PCOS patients with ovulatory dysfunction. METHODS: The relative expression of CC-PTX3 and CC-VDR-X2 mRNA were evaluated using qRT-PCR in a total of 79 CC samples collected from individual cumulus-oocyte complex of 40 infertile patients (20 PCOS and 20 non-PCOS normal responders) who underwent ovarian stimulation with the GnRH antagonist protocol. RESULTS: Relative PTX3 mRNA expressions of CCMI-control and CCMII-control showed 3- and 9-fold significant upregulation compared to CCGV-control, respectively. The relative PTX3 mRNA expression of CCMII-control increased approximately three fold compared to CCMI-control. Compared to CCGV-pcos, a 3-fold increase was noted in the relative PTX3 mRNA expression of CCMI-pcos and an approximately 4-fold increase in the PTX3 mRNA expression of CCMII-pcos. Relative PTX3 mRNA expression values of CCMII-pcos and CCMI-pcos were similar. A 6-fold upregulation of relative PTX3 mRNA and a 4-fold upregulation of VDR-X2 mRNA were detected in CCMII-control compared to CCMII-pcos. CC-VDR-X2 expression patterns of the PCOS and control groups overlapped with the CC-PTX3 pattern. Fertilization rates of the PCOS group exhibiting failed transcript expression were similar to normal responders. CONCLUSION: The fact that relative CC-PTX3 and CC-VDR mRNA expression does not increase during the transition from MI to MII stage in PCOS as in normal responders suggests that PTX3 and VDR expression may be defective in cumulus cells of PCOS patients with ovulatory dysfunction.

Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal.

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes' maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy.

Intra-ovarian stem cell transplantation in management of premature ovarian insufficiency: towards the induced Oogonial Stem Cell (iOSC).

The specialized resident-stem cells in gonads are tasked with restorating damaged ovarian cells following injury to maintain sequential reproductive events. When we talk about premature ovarian insufficiency (POI) we accept the existence of decreased stem cell and their regenerative abilities. The present study was to explain how restorating damaged ovarian cells following injury to maintain sequential reproductive events in evidence-based medicine indexed in PubMed and Web of Science. The exact mechanism is unclear stem cells transfer may improve compromised ovarian function and fertility outcome in women with POI. Soluble factors secreted by stem cell may rescue impaired mitochondrial function in oogonial stem cells, enhance metabolic capacity of resident stem cells, induce local neovascularization in the ovary, and activate gene shifting between transferred stem cells and germ cell precursors. This review may provide insight into how stem cells show some of their beneficial effects on compromised ovarian microenvironment and germ cell niche and paves the way for clinical trials for improving ovarian function of women with POI. We also had the opportunity to share our hypothesis about the design and development of induced oogonial stem cell (iOSC) and its use in POI.

Combating sars-cov-2 through lipoxins, proteasome, caveolin and nuclear factor-κb pathways in non-pregnant and pregnant populations.

It can be misleading to think that the new severe acute respiratory syndrome coronavirus (SARS-CoV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells. Despite all the precautions taken, the pandemic attack continues and the rapid increase in the number of deaths suggest that this virus has entered the cell through different pathways and caused damage through different mechanisms. The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis. SARS-CoV-2 has to use nuclear factor-κB (NF-kB), caveloae, clathrin, lipoxin, serine protease and proteasome pathways in addition to ACE2 to enter the target cell and initiate damage. For this reason, while new drug development studies are continuing, in order to be beneficial to patients in their acute period, it is imperative that we are able to come up with drugs that activate or inhibit these pathways and are currently in clinical use. It is also critical that we adopt these new pathways to the treatment of pregnant women affected by SARS-CoV-2, based on the scientific data we use to treat the general population.

Molecular role of peptides/proteins in subfertility of polycystic ovarian syndrome.

Obesity and hyperandrogenemia are known to have adverse effects on both developing follicle and endometrium receptivity in polycystic ovarian syndrome (PCOS). Insulin resistance also contributes to this dilemma as a cause or a consequence and leads to worsening of the clinical picture. The difficulty in obtaining pregnancy despite the presence of a large number of oocyte has concentrated our attention on oocyte quality and development. However, the occurence of subfertility has also caused us to investigate the presence of different etiologic agents in non-obese PCOS women with normal androgen and insulin levels. In this context peptides have become the most accused and investigated molecules in cases of impaired fertility due to PCOS. Most of the studies investigating the relationship between PCOS and peptide did not support each other. The difficulties in measuring peptide levels as well as the individual variations in peptide synthesis and release are possible causes of this incongruity. For all these reasons, the incorporation of studies investigating the relationship between PCOS, peptide and subfertility in an article has become critical to pioneering future work. Understanding the association between peptides and subfertility will help us to understand the effects of peptides on failed fertility in PCOS. Moreover, updating our knowledge about peptides may allow us designing new drugs to to treat subfertility in PCOS. This review provides a general summary of the mechanisms of action of neuroendocrine peptides in regulating reproductive events. Since it is not usual to discuss all peptides in this context, only the effects of key central and peripheral peptides on fertility in PCOS have been extensively addressed.

Nppc/Npr2/cGMP signaling cascade maintains oocyte developmental capacity.

The follicle must fulfill the following criteria if it is to survive the period between early embryonic life and the luteinizing hormone (LH) peak. It should (i) be surrounded by pregranulosa cells; (ii) complete the first meiotic division and become dormant; and (iii) continue metabolism during the dormant stage. Interaction between the natriuretic peptide precursor type C (Nppc) and its receptor, natriuretic peptide receptor 2 (Npr2), affects female fertility through the production of oocytes with developmental capacity and maintain oocyte meiotic arrest. While Nppc is expressed in mural cells, cumulus cells express Npr2. Nppc/Npr2 system exerts its biological function on developing follicles by increasing the production of intracellular cyclic guanosine monophosphate (cGMP). This pathway not only contributes to the development of ovary and the uterus, but aids the formation of healthy eggs in terms of their morphological and genetic aspects. A defect in this pathway leads to asmall ovarian size, string-like uterine horns, and thin endometrium and myometrium. Disorganized chromosomes, abnormal cumulus expansion and early meiotic resumption occur in animals with defective Nppc/Npr2 signaling. The types and number of oocytes also decrease when there is incompetent Nppc/Npr2 signaling. This paper extends on most recent and relevant experimental evidence regarding Nppc/Npr2/cGMP signaling with regard to its crucial role in maintaining oocyte meiotic arrest and the production of oocytes with developmental capacity. We further discuss whether the agonist or antagonist forms of the members of this exciting pathway can be usedfor triggering final oocyte maturation.

Navigation problems of ICSI or naive blastocyst can be solved with artificial blastocyst.

Embryos have evolved a remarkable capacity to find implantation site. The impressive navigation ability of natural blastocysts may rely on highly sensitive signals arising from embryos and specialized signal processing strategies in the endometrium. Navigation capabilities may be compromised in ICSI embryos because of altered biochemical signaling. The design and delivery of artificial blastocyst (AB) carrying strong chemical signals may allow ICSI embryos to more easily locate to and be retained in the implantation zone. ICSI embryos will attach easily to the implantation zone after it is found by the AB. Co-transfer of the AB together with the ICSI embryo may overcome potential difficulties in implantation due to impaired embryo-maternal communication in cases with implantation failure.

Patatin-like phospholipase domain containing 3-gene (adiponutrin), preptin, kisspeptin and amylin regulates oocyte developmental capacity in PCOS.

This study was planned to test whether follicular fluid (FF) levels of patatin-like phospholipase domain containing 3-gene (PNPLA3:adiponutrin), preptin, kisspeptin, and amylin change in polycystic ovarian syndrome (PCOS). A total of 40 infertile volunteers undergoing IVF/ICSI were included in the study. They were divided into two groups as PCOS (n=20) and control group without PCOS (n=20). The controls were recruited from subjects with a poor ovarian response. The PCOS and control participants were matched according to their body mass index (BMI). Each group of participants underwent ovarian stimulation with GnRH antagonist protocol. Blood and FF samples of one dominant follicle were obtained from each subject during the oocyte pick-up. FF and serum levels of PNPLA3, preptin, kisspeptin and amylin were measured through ELISA. Amylin and adiponutrin median values were not different according to study groups (p>0.05). FF-preptin median values in the control group were similar to the serum preptin values of control and PCOS groups (Z=0.970, p=1.000 and Z=2.631, p=0.051, respectively). Medians of the serum preptin in control and PCOS groups were the same (Z=1.649; p=0.595). FF-preptin median values of PCOS group were significantly lower than the preptin median values of the control group. Serum preptin levels were positively correlated with HOMA-IR, but not with pregnancy rates and the number of retrieved oocytes. Serum kisspeptin levels were negatively correlated with the number of retrieved oocytes and pregnancy rates. While amylin and adiponutrin have no role in the folliculogenesis, kisspeptin and preptin work together for regulating follicle developmental capacity in PCOS.

Serum salusins levels are increased and correlated positively with cyst size in ovarian endometrioma.

OBJECTIVES: The objective of this study is to evaluate plasma concentrations of salusin-α and salusin-ß levels in women with endometrioma and non-endometriotic benign ovarian cysts. METHOD: Endometrioma patients (n = 14), non-endometriotic ovarian cysts (n = 14), and age-matched normal healthy fertile subjects (n = 14) participated in this study. Plasma salusin-α and salusin-ß levels at the time of mid-luteal phase before and 3 months after L/S cystectomy were measured using ELISA and EIA tests, and their relation with demographic parameters was also assessed. RESULTS: The mean salusin-α and salusin-ß levels were significantly higher in women with endometrioma before the removal of cyst compared with cases with non-endometriotic cyst and fertile cases. Surgical removal of the endometrioma decreased the mean salusin-α and salusin-ß levels to the level of those with non-endometriotic cyst before and after the cystectomy and fertile women, in both unilateral and bilateral endometrioma cases. Plasma salusin-ß concentrations were found to be positively correlated with age, size of cyst, bilaterality, and salusin-α levels. Salusin-ß values showed no correlations to BMI and size of the ovarian cysts. CONCLUSIONS: Plasma salusin-α and salusin-ß levels are increased in endometrioma patients and positively correlated with endometrioma size. Laparoscopic removal of the endometrioma by stripping technique decreases the salusin levels to a similar level of fertile women.

Differences in geographical distribution and risk factors for urinary incontinence in Turkey: analysis of 6,473 women.

OBJECTIVE: To assess the prevalence, types and risk factors for urinary incontinence (UI) and to evaluate the impact of incontinence on quality of life by using validated and objective questionnaires in the western and eastern parts of Turkey. METHODS: In this multicenter observational study, 6,473 women from 38 cities in the western and eastern parts of Turkey were included. UI was assessed by ICIQ-SF (International Consultation on Incontinence Questionnaire Short Form) and IIQ-7 (Incontinence Impact Questionnaire). RESULTS: The UI rate was 20.9% (10% for stress, 8.3% overactive bladder and 2.6% for mixed type). In all, stress incontinence was the most common type. The rate of UI in women residing in the west was higher than in women living in the east (p < 0.001). ICIQ scores were comparable in the two groups but women in the west scored higher in each item of the IIQ. Age >40 years (p < 0.001), number of siblings >5 (p < 0.001) and low educational status (p < 0.001) increased the rate of incontinence. In binary logistic regression analysis menopausal status, age >40 years, number of siblings >5, being overweight, region of residence, and educational status were associated with UI. CONCLUSION: The rate of UI in women residing in the western part of Turkey was higher than women living in the east. Residing in a different geographical region (in our case living either in the western or eastern part of Turkey) seemed to be an independent risk factor for UI. Moreover, UI deteriorates quality of life and more attention should be paid to this vulnerable population.

Serum orexin-A (OXA) level decreases in polycystic ovarian syndrome.

AIM: In the current study, we aimed to investigate whether serum orexin-A (OXA) levels are different in polycystic ovary syndrome (PCOS) subjects. MATERIALS AND METHODS: Thirty-six women with PCOS and 40 healthy, age and body mass index-matched controls were included in the prospective cross-sectional study. All subjects underwent venous blood draws during the early follicular phase after overnight fasting. Serum OXA levels were measured with an enzyme immunoassay (EIA). The relationships between the serum OXA levels and the anthropometric and metabolic parameters were also assessed. RESULTS: The serum OXA levels were lower in the women with PCOS compared to the control group. The serum OXA levels were correlated negatively with systolic blood pressure, the Ferriman-Gallway score and LH and free testosterone levels. CONCLUSION: Our results indicate that serum OXA levels decrease in the serum of women with PCOS.

Salusins, newly identified regulators of hemodynamics and mitogenesis, increase in polycystic ovarian syndrome.

In the current study, we aimed to investigate whether serum salusin α and ß levels are different in PCOS subjects. Fifty women with PCOS and 50 healthy, age- and body mass index matched controls were included to the prospective cross-sectional study. All subjects underwent venous blood drawing on the early follicular phase after an overnight fasting. Serum salusin α and ß levels were measured with EIA, and ELISA respectively. The relationships between serum salusin levels and anthropometric and metabolic parameters were also assessed. Plasma salusin α and ß levels were higher in women with PCOS compared to control group. Serum salusin α level correlated positively with salusin ß and fasting serum insulin levels. The serum salusin ß levels were correlated positively with HOMA-IR, TG, LDL-C, LH, FSH, and total testosterone levels. Our results indicate that salusins, newly identified regulators of hemodynamics and mitogenesis, are increased within the serum of women with PCOS.

Maternal and fetal serum orexin-A levels in gestational diabetes mellitus.

AIM: Evidence suggests that orexin regulates food consumption, glucose metabolism and insulin secretion. Orexin may have a role in the pathogenesis of type II diabetes mellitus, however its role in gestational diabetes mellitus is not known. We aimed to assess maternal serum and cord blood orexin-A (OXA) concentrations in pregnant women with gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Thirty-five pregnant women with GDM and 35 gestational-age-matched healthy pregnant subjects participated in the study. Maternal serum and cord blood OXA levels were measured with enzyme immunoassay at the time of birth. The correlations between maternal serum and cord blood OXA levels, anthropometric and metabolic parameters were also assessed. RESULTS: The mean maternal and cord serum OXA (1.16±0.37 and 1.35±0.20ng/mL, respectively) in the GDM group were significantly different from those of the controls (1.58±0.59 and 1.25±0.21ng/mL, respectively). The mean maternal fasting-glucose-to-OXA ratio was significantly higher in the GDM group. In the GDM group, the mean maternal serum OXA levels were similar in the insulin (n=24) and diet (n=11) treated cases, respectively (1.13±0.36ng/mL and 1.21±0.41ng/mL). Maternal serum OXA levels positively correlated with fetal serum OXA and maternal glucose levels. OXA concentrations in maternal serum were negatively correlated with the fasting glucose, fasting insulin and homeostasis model assessment insulin resistance index. CONCLUSIONS: Maternal serum OXA levels decrease, and fetal serum OXA levels increase in women with GDM.

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin-releasing hormone agonist and antagonists, on follicular fluid stem cell factor and serum urocortin 1 levels on the day of oocyte retrieval.

PURPOSE: To compare the serum and follicular fluid (FF) concentrations of stem cell factor (SCF) as well as the serum urocortin 1 (UCN1) concentration in gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) protocols for controlled ovarian hyperstimulation (COH) in IVF patients. METHODS: Follicular fluids and blood samples of 42 infertile women undergoing COH for IVF-embryo transfer with either GnRH agonist (n = 22) or GnRH antagonist (n = 20) protocols from 2010 to 2011 were collected during oocyte retrieval. SCF concentrations of serum and FF were assessed by sandwich enzyme immunoassay using ELISA Kit for SCF kid. Serum UCN1 concentration were measured using commercially available enzyme-linked immunosorbent assay. RESULTS: Concentrations of serum UCN1, serum and FF SCF were similar in the two groups. The serum SCF levels correlated strongly with the follicular SCF levels (r = 0.770, p < 0.001). The mean implantation rate, biochemical and clinical pregnancy rate and live birth rate per cycle were also similar in the groups. CONCLUSIONS: These observations suggest that there is no significant difference in follicular microenvironment in terms of SCF and UCN1 between agonist and antagonist protocols.

Endometrial Injury Upregulates Expression of Receptivity Genes in Women with Implantation Failure.

BACKGROUND: Homeobox genes A10 (HOXA10) and A11 (HOXA11), members of the abdominal B gene family, are responsible for embryonic survival and implantation. This study was planned to investigate whether endometrial injury alters the expression of both transcripts in women with implantation failure. METHODS: A total of 54 women with implantation failure were divided into two equal groups as experimental (scratching) and sham (no scratching). Participants in the scratching group were exposed to endometrial injury in the mid-luteal phase, and those in the sham group were exposed to endometrial flushing. The scratching group, but not the sham group, underwent prior endometrial sampling. A second endometrial sampling was performed on the scratching group in the mid-luteal phase of the following cycle. The mRNA and protein levels of the HOXA10 and 11 transcripts were determined in endometrial samples collected before and after injury/flushing. Participants in each group underwent IVF/ET in the cycle after the second endometrial sampling. RESULTS: Endometrial injury caused a 60.1-fold (p < 0.01) increase in HOXA10 mRNA and a 9.0-fold increase in HOXA11 mRNA (p < 0.02). Injury resulted in a significant increase in both HOXA10 (p < 0.001) and HOXA11 protein expression (p < 0.003). There was no significant change in HOXA10 and 11 mRNA expressions after flushing. Clinical pregnancy, live birth, and miscarriage rates of the both groups were similar. CONCLUSIONS: Endometrial injury increases homeobox transcript expression at both mRNA and protein levels.

Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban.

PURPOSE: The purpose of this study was to evaluate the cardiac and cerebral oxidative stress in the offspings of pregnant rats treated with oxytocin antagonist atosiban. METHODS: Experimentally naive, adult female Wistar-albino rats (200-250 g) were mated with adult male rats for copulation. After confirming pregnancy, eight gravid rats were then randomly assigned into two equal groups. The animals were treated from days 15 to 20 of gestation. One group acted as a control group, and received intraperitoneal (i.p.) injections of saline in a daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p. atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and brain tissues of the newborn rats were dissected and sent for the measurement of total oxidant status, total antioxitant status and oxidative stress index. RESULTS: There was no significant difference in birthweight or in the number of pups between two groups. Newborns from atosiban-treated mothers showed significantly increased oxidative stress in the plasma and heart tissue than that of controls which was confirmed by histological examination (P < 0.05). Oxidative stress parameters and histopathological results of the brain tissues of newborns were similar between two groups (P > 0.05). CONCLUSION: Oxytocin receptor blockage for the treatment of premature delivery may be associated with increased fetal morbidity and mortality secondary to the elevated oxidative stress in the heart of the newborns.

Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in PCOS.

The aim of this study was to establish the frequency of angiotensin-converting enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with polycystic ovary syndrome (PCOS) and to examine the association of this polymorphism with insulin resistance. A total of 32 women with PCOS and 31 healthy, age- and body mass index-matched controls were studied. Serum lipids, fasting glucose, insulin and other hormones concentrations were measured. Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR). DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D polymorphism was carried out by polymerase chain reaction. ACE genotypes were distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in four (12.9%) of healthy subjects. The frequency of D and I alleles were found in 69% and 31% of the PCOS group and 55% and 45% in the control group, respectively. There were no significant differences regarding the genotypic distribution and allelic frequency between the groups. However the ACE DD genotype was significantly associated with serum insulin concentrations and HOMA-IR measurement (both P=0.005). ACE DD genotype is associated with an increased insulin resistance in women with PCOS.

Baboon syndrome induced by oral antitussive-decongestant agent in a child.

We present the case of a three-year-old boy who developed a special exanthem after oral intake of an antitussive-decongestant agent. The clinical findings were compatible with baboon syndrome. To our knowledge, this is one of the rare reported cases of baboon syndrome associated with use of an antitussive-decongestant including pseudoephedrine HCI, dextromethorphan HBr and chlorpheniramine maleate.

Laparoscopic Ovarian Drilling Improves Endometrial Homeobox Gene Expression in PCOS.

The study was designed to investigate whether laparoscopic ovarian drilling (LOD) of ovaries alters the expression levels of HOXA-10 and HOXA-11 mRNA in the endometrium of infertile women with clomiphene-resistant PCOS. Expression of HOXA-10 and HOXA-11 mRNA in the endometrium obtained before and after LOD during the midsecretory phase was measured. Expression of each gene was evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Expression levels of HOXA-10 and HOXA-11 mRNA were lower in endometrium of patients with PCOS before LOD compared with fertile controls. But the differences failed to show statistical significance. Compared with fertile subjects, LOD of PCOS ovaries up-regulated endometrial HOXA-10 and HOXA-11 mRNA expression. Fold changes of HOXA-10 and HOXA-11 mRNA after LOD were found to be 4.46 and 4.19, respectively. Fold change increase in HOXA-10 and HOXA-11 mRNA was found to be statistically significant (P < .01, P < .02). There is a receptivity defect in the endometrium of women with PCOS that affects fertility regardless of other causes of infertility. LOD increases endometrial HOXA-10 and HOXA-11 mRNA expressions and improves receptivity in patients with clomiphene-resistant PCOS.

Genome-wide expression analysis of endometrium before and after endometrioma surgery.

OBJECTIVE: This study was planned to investigate possible alteration in the number of differentially expressed genes (DEGs) in eutopic endometrium before and after laparoscopic removal of the ovarian endometrioma. STUDY DESIGN: Six infertile women with ovarian endometrioma who underwent laparoscopic endometrioma cystectomy and six fertile control subjects who underwent tubal sterilization were included the study. Endometrial samples were collected before and 3 months after surgery throughout the mid-luteal phase. Genome-wide expression profiling was performed with Illumina Human HT-12V4 microchip, a high density silica bead-based microarray which utilizing more than 47.000 probs. Illumina microsequence system was used to assess detection of p value for each probe in every sample. Probes revealing significant assessment (p < .05) were selected for comparative analysis. RESULTS: We have detected 1478 DEGs in the comparison between endometrium of women with endometrioma and fertile controls. 118 out of 1478 genes (7.9 %) were significantly increased or decreased more than 1.5-fold in their expression. When the preoperative values of the control and patient groups are compared the number of DEGs was 243 (7.5 %). In 9 out of 243 genes, the fold change was found to be 1.5 and more (3.7 %). Comparison of the number of DEGs after endometrioma surgery and tubal ligation revealed that expression patterns of 1036 genes (33.7 %) were changed in endometrioma group. In 105 out of 1036 genes, the fold change was found to be 1.5 and above (10 %). A comparison using 2706 probes revealed changes in the expression patterns of 106 different genes (3.9 %) after endometrioma resection. In 4 out of 106 genes, the fold change was found to be 1.5 and above (3.7 %). The comparison using 6035 probes revealed changes in the expression patterns of 93 genes (1.5 %) after tubal ligation. None of the 93 genes had a fold change of 1.5 or higher. The number of DEGs in endometrioma groups after surgery was approximately 3-fold higher than control group. CONCLUSIONS: Endometrium of women with endometrioma displayed abnormal expression of genes associated with implantation, immunological, endocrine and neuracrine functions. Positive alteration of the expression pattern of DEGs and signal transduction pathways following endometrioma surgery can improve the receptive capacity and implantation rates of eutopic endometrium.