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Endocrinology AND Infertility, female [keywords]
- Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. [JOURNAL ARTICLE]
- Reprod Biomed Online 2014 Jul 10.
Unexplained recurrent spontaneous abortion (RSA) might be caused by the mother's immunological rejection of the fetus. In this cross-sectional study, the percentage of T helper 17 (Th17), T regulatory (Treg) cells and their cytokines as the main players of immunomodulation in peripheral blood lymphocytes during the luteal phase of 20 women with unexplained RSA were compared with 20 normal non-pregnant women. The percentage of Treg cells in the former was significantly lower compared with controls. The percentage of Th17 cells in the former was higher than controls. Expression of IL-23, IL-17, IL-6 cytokines in the former was significantly higher than controls, but the higher expression of IL-21 was not significant. The gene expression of TGF-β and FoxP3 in the former was lower than controls. Significant positive correlations were found between the percentage of Th17 cells with IL-23, IL-6 and IL-17 and between expression of IL-23 and IL-6 and IL-17. IL-6 gene expression showed a significant positive correlation with IL-17. Therefore, imbalance of Th17-Treg cells and the consequent changes in cytokine expression might be implicated in the pathogenesis of unexplained RSA and may provide new insight into the immunoregulatory events at the maternal-fetal interface.
- Gestational diabetes mellitus risk factors in women with polycystic ovary syndrome (PCOS). [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2014 Aug 7.:195-199.
To compare the incidence of gestational diabetes mellitus (GDM) in Iranian infertile women with polycystic ovary syndrome (PCOS) and women without PCOS after pregnancies resulting from either assisted reproductive technology (ART) or spontaneous as well as to determine the risk factors of GDM in PCOS women.In a cross-sectional study, we evaluated medical records of 234 spontaneous pregnant women without PCOS in Akbarabadi Women's Hospital affiliated to Tehran University of Medical Science, Tehran, Iran, along with 234 pregnant women with PCOS and 234 pregnant non-PCOS women with ART conception who were treated at Royan institute, Tehran, Iran, at the same period of time, 2012 to February 2013. Exclusion criteria were as following: maternal age ≥40, family history of diabetes in first-degree relatives, pre-pregnancy diabetes and history of gestational diabetes, history of stillbirth, recurrent miscarriage, birth weight baby ≥4kg (macrosomia), parity >4, Cushing's syndrome, congenital adrenal hyperplasia and overt hypothyroidism. The GDM diagnosis was according to American Diabetes Association (ADA) criteria. Incidence and the risk factors for GDM were evaluated.The incidence rates of GDM were 44.4%, 29.9% and 7.3% for PCOS ART, non-PCOS ART and non-PCOS spontaneous pregnant women, respectively. Multivariable logistic regression was used for determining risk factors of GDM in PCOS women with adjusted odds ratios for age, parity and hypothyroidism, the results revealed the most important and significant predictors for development of GDM in PCOS women as follow: menstrual irregularity (OR=4.2; 95% CI=1.7-10.6), serum triglycerides level ≥150mg/dL (OR=1.9; 95% CI=1.07-3.6) and pregestational metformin use (OR=0.4; 95% CI=0.2-0.7).Pregnant Iranian women with a history of infertility and PCOS are at increased risk for developing GDM. It is recommendable to perform screening test for GDM in PCOS women with ART treatment, irregular menses and high serum triglycerides level in the early stage of pregnancy. Pregestational use of metformin can be effective in reducing the occurrence of GDM.
- Mayer-rokitansky-kuster-hauser syndrome associated with severe inferior vena cava stenosis. [Journal Article]
- Case Rep Obstet Gynecol 2014.:745658.
Precis. The postoperative course of a neovagina creation procedure in a young woman with Meyer-Rokitansky-Kuster-Hauser syndrome was complicated, despite prophylaxis, by extensive pelvic deep venous thrombosis secondary to unsuspected severe inferior vena cava stenosis.
Background.Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital vaginal agenesis and an absent or rudimentary uterus in genotypical females. Malformations of the inferior vena cava (IVC) are not commonly associated with MRKH syndrome. We report a case of a patient with MRKH syndrome with severe IVC stenosis that was diagnosed when the patient presented with extensive pelvic deep venous thrombosis (DVT) during the postoperative course of a neovagina creation. Case. A 19-year-old female underwent a McIndoe procedure. Despite DVT prophylaxis, extensive pelvic DVT of the femoral vein was diagnosed on postoperative day 7. Therapeutic anticoagulation was initiated, and pharmacological and mechanical thrombolysis were performed. During these procedures, a hypoplastic IVC was noted.
Conclusion.MRKH syndrome can be associated with IVC malformations, which constitute an anatomical risk factor for postoperative DVT.
- VEGFR-1 blockade disrupts peri-implantation decidual angiogenesis and macrophage recruitment. [Journal Article]
- Vasc Cell 2014.:16.
Angiogenesis and macrophage recruitment to the uterus are key features of uterine decidualization; the progesterone-mediated uterine changes that allow for embryo implantation and initiation of pregnancy. In the current study, we characterized the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) in macrophages and endothelial cells of the peri-implantation uterus and determined if VEGFR-1 function is required for decidual angiogenesis, macrophage recruitment, and/or the establishment of pregnancy.Expression of VEGFR-1 in uterine endothelial cells and macrophages was determined with immunohistochemistry. To assess the effect of continuous VEGFR-1 blockade, adult female mice were given VEGFR-1 blocking antibody, MF-1, every 3 days for 18 days. After 6 doses, females were mated and a final dose of MF-1 was given on embryonic day 3.5. Endothelial cells and macrophages were quantified on embryonic day 7.5. Pregnancy was analyzed on embryonic days 7.5 and 10.5.F4/80(+) macrophages are observed throughout the stroma and are abundant adjacent to the endometrial lumen and glands prior to embryo implantation and scatter throughout the decidua post implantation. VEGFR-1 expression is restricted to the uterine endothelial cells. F4/80(+) macrophages were often found adjacent to VEGFR-1(+) endothelial cells in the primary decidual zone. Continuous VEGFR-1 blockade correlates with a significant reduction in decidual vascular and macrophage density, but does not affect embryo implantation or maintenance of pregnancy up to embryonic day 10.5.We found that VEGFR-1 functions in both decidual angiogenesis and macrophage recruitment to the implantation site during pregnancy. VEGFR-1 is expressed by endothelial cells, however blocking VEGFR-1 function in endothelial cells results in reduced macrophage recruitment to the uterus. VEGFR-1 blockade did not compromise the establishment and/or maintenance of pregnancy.
- Toll-like receptors expression in follicular cells of patients with poor ovarian response. [Journal Article]
- Int J Fertil Steril 2014 Jul; 8(2):183-92.
Poor ovarian response (POR) to gonadotropin stimulation has led to a significant decline in success rate of fertility treatment. The immune system may play an important role in pathophysiology of POR by dysfunctions of cytokines and the growth factor network, and the presence of ovarian auto-antibodies. The aim of this study is to investigate the expression of toll-like receptors (TLR) 1, 2, 4, 5, 6 and cyclooxygenase (COX) 2 genes in follicular cells and concentration of interleukin (IL)-6, IL-8 and macrophage migration inhibitory factor (MIF), as major parts of innate immunity, in follicular fluid (FF) obtained from POR women in comparison with normal women.In this case-control study, 20 infertile POR patients and 20 normal women took part in this study and underwent controlled ovarian stimulation. The FF was obtained from the largest follicle (>18 mm). The FF was centrifuged and cellular pellet was then used for evaluation of expression of TLRs and COX2 genes by real-time PCR. FF was used for quantitative analysis for IL-6, IL-8 and MIF by enzyme-linked immunosorbent assay (ELISA).TLR1, 2, 4, 5, 6 and COX2 gene expression were significantly higher in POR (p<0.05). Concentration of IL-6, IL-8 and MIF proteins was significantly increased in POR compared with normal women (p<0.05).These findings support the hypothesis that the immune system may be involved in pathophysiology of POR through TLRs.
- Health-Related Quality of Life and Primi-Gravid: A Comparative Study of Natural Conception and Conception by Assisted Reproduction Technologies (ARTs). [Journal Article]
- Int J Fertil Steril 2014 Jul; 8(2):167-74.
Childbearing for the first time is a unique experience. Quality of life is an important indicator in health studies. This study aimed to assess the quality of life of women who were conceived by ARTs and had successful childbirth for the first time and to compare it with quality of life in women who become pregnant naturally and similarly had successful childbirth for the first time.This was a cross sectional comparative study. The accessible sam- ple was recruited from patients attending an infertility clinic and two obstetric and gynecology clinics in Tehran, Iran, during March 2010 to March 2011. In all 276 patients were approached. Of these, 162 women (76 women in natural conception group and 86 women in assisted reproduction technologies group) who met the inclusion criteria were entered into the study. Quality of life was assessed using the 36-item Short Form Health Survey (SF-36). Women completed the questionnaire at two time points: i. last trimester and ii. first month after delivery. Comparison was made between two groups using Mann-Whitney U test and paired samples t test.Comparing the SF-36 scores between women in natural conception group and ARTs group before childbirth, it was found that natural group had better condition on physical functioning, role limitation due to physical problems, bodily pain and social functioning, while the ARTs group reported better status on general health, vitality, role limitation due to emotional problems, and mental health. However, after childbirth, the ARTs group reported a better condition almost on all measures, except for physical functioning. Comparing differences in obtained scores between two groups before and after childbirth, the results showed that improvements in health related quality of life measures for the ARTs group were greater in all measures, expect for general health.The findings from this study suggest that health-related quality of life was improved in women who became a mother for the first time by either method. Comparing to women who became mother by natural conception, women who received ARTs showed better quality of life from this first successful experience.
- Expression of Toll-like receptors 7-10 in human fallopian tubes. [Journal Article]
- Iran J Reprod Med 2014 Jun; 12(6):389-94.
The human female reproductive tract (FRT) is constantly deal with the invading pathogens. Recognition of these pathogens is attributed to the family of Toll like receptors (TLR) as a major part of the innate immune system. We and others have previously revealed that TLRs1-6 express in the female reproductive tract. However, more studies should be done to detect TLRs 7-10 in the female reproductive tract, especially in the fallopian tubes.To examine the expression of TLRs7-10 in human fallopian tube tissue.Using immunostaining techniques, distribution of TLR7-10 was studied in surgical sections from the uterine tubes, obtained from patients undergoing tubal ligation and hysterectomy for benign gynecological conditions. RT-PCR was used to show the existence of TLR7-10 genes in fallopian tube tissue.TLR7-10 proteins were detected in the fallopian tube epithelium, although the intensity of staining was not equal in cases. TLR7-10 genes were expressed in human fallopian tube tissue.This study indicates that TLR7-10 is expressed in fallopian tubes tissues, and may play an important role in microbial recognition, and in host defense against ascending infection.
- Role of advanced glycation end-products in obesity-related ovarian dysfunction. [Journal Article]
- Minerva Endocrinol 2014 Sep; 39(3):167-74.
Obesity affects ovarian function, one of the main regulators of female fertility. Tissue levels of the proinflammatory advanced glycation end-products (AGEs) and their receptors (RAGE) are elevated in obesity. AGEs are key contributors to perturbations in the ovarian microenvironment. On this basis, the present review focuses on clinical and experimental studies supporting the role of AGE-RAGE system as a contributor to obesity-related ovarian dysfunction. Particular emphasis has been given to changes in AGEs, RAGE and the anti-inflammatory soluble receptor (sRAGE) levels in obesity state and following dietary interventions (high-fat diet and weight loss). Ovarian sensitivity, in particular granulosa cell function and oocyte meiosis, to the pro-inflammatory AGE-RAGE system as well as the relationship of follicular fluid AGEs and sRAGE to in vitro fertilization outcome are also discussed. Overall, obesity, with its alterations in the AGE-RAGE system, can disrupt the ovarian microenvironment potentially compromising oocyte competence and fertility. This review underscores a critical need to uncover the mechanistic actions of AGE-RAGE system in obesity-related ovarian dysfunction. Clinical and basic studies focusing on elucidating the patterns of accumulation and role of the AGE-RAGE system in human ovarian follicles are key steps in understanding their contribution to the health of human oocytes and embryos.
- Over-expression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 22.:en20141339.
Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal (HPG) axis. As corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, we tested the hypothesis that over-expression of CRF in the CeA of female rats alters anxiety behaviour, dysregulates the HPA axis response to stress, changes pubertal timing and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of pre-weaning (postnatal day 12) female rats. Over-expression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced, but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats over-expressing CRF. Despite the absence of change in basal or stress (lipopolysaccharide or restraint) induced corticosterone secretion, over-expression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in post pubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.
- Ovarian adult stem cells: hope or pitfall? [REVIEW]
- J Ovarian Res 2014.:71.
For many years, ovarian biology has been based on the dogma that oocytes reserve in female mammals included a finite number, established before or at birth and it is determined by the number and quality of primordial follicles developed during the neonatal period. The restricted supply of oocytes in adult female mammals has been disputed in recent years by supporters of postnatal neo-oogenesis. Recent experimental data showed that ovarian surface epithelium and cortical tissue from both mouse and human were proved to contain very low proportion of cells able to propagate themselves, but also to generate immature oocytes in vitro or in vivo, when transplanted into immunodeficient mice ovaries. By mentioning several landmarks of ovarian stem cell reserve and addressing the exciting perspective of translation into clinical practice as treatment for infertility pathologies, the purpose of this article is to review the knowledge about adult mammalian ovarian stem cells, a topic that, since the first approach quickly attracted the attention of both the scientific media and patients.