Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study aims to evaluate whether serum vascular endothelial growth factor (VEGF) levels, before treatment with gonadotropins, may be considered a predictive marker of moderate ovarian hyperstimulation syndrome (OHSS). At the University of Pisa hospital infertility unit we have retrospectively selected 10 patients who developed moderate forms of OHSS and 30 control patients who presented a normal response to ovarian stimulation among 400 women undergoing in vitro fertilization (IVF). Serum samples were collected before starting pFSH administration (150-300 IU/day). VEGF levels in serum were measured. No statistically significant difference was found between the serum VEGF levels of patients who developed moderate forms of OHSS and women without any symptoms of the syndrome. Further, serum VEGF concentrations were not significantly correlated with the age of the patients, the number of international units of FSH administered during the cycle of stimulation, the follicle and oocyte numbers counted on the day of the egg retrieval or estradiol levels detected on the same day. This study demonstrates that serum VEGF levels, before starting gonadotropin treatment, are not predictive of the subsequent development of moderate forms of ovarian hyperstimulation syndrome.
 ...
PMID:Serum vascular endothelial growth factor levels before starting gonadotropin treatment in women who have developed moderate forms of ovarian hyperstimulation syndrome. 1059 47

We review three complications of ovarian stimulation, namely ovarian hyperstimulation syndrome, thromboembolic disease in relation to fertility treatment and multiple pregnancy. Current views on the ovarian hyperstimulation syndrome emphasize its association with the presence of polycystic ovaries. We review here the pathophysiological background of this association and focus on the central role of vascular endothelial growth factor (VEGF). Overexpression of VEGF in the polycystic ovary is thought to contribute to its characteristic multifollicular response to gonadotrophic stimulation. Release of large amounts of VEGF into the circulation is thought to account for the development of the clinical syndrome of ovarian hyperstimulation. The implications of this understanding are explored and the clinical features of the condition and its management are described. Thromboembolic disease is increasingly recognized as a serious if rare complication of infertility treatment. The subject is reviewed here with special reference to two recently published and important papers. The most concerning complication of infertility treatment is multiple pregnancy. Few doctors seem to be aware of the dire statistics: every index of obstetric outcome is adversely affected. The survival, health and family circumstances of children born as the result of multifetal gestation are all impaired. Infertility patients need a clear understanding of the risks involved so that they can appreciate the need for intensive monitoring of ovarian stimulation. In our opinion a knowledge of the rate of multiple pregnancy is quite as important as knowing the clinic's 'success' rate.
 ...
PMID:Complications of ovarian stimulation. 1062 68

The use of in-vitro fertilization (IVF) as a therapeutic tool in patients with endometriosis has provided information about the disease and, in particular, aspects of the reproductive process in humans, particularly folliculogenesis, fertilization, embryo development and implantation. Retrospective analyses of IVF and oocyte donation programmes showed impaired implantation in patients with endometriosis. Otherwise, the observation that embryo development was blocked more frequently in cases of endometriosis, suggested that impaired embryo quality may be responsible for the reduced implantation rates. Similarly, women with the disease undergoing oocyte donation had the same chance of implantation as patients without endometriosis, suggesting that the endometrial milieu is not affected in patients with endometriosis. The quality of the oocyte may, therefore, be altered in patients with endometriosis. To investigate this, we studied steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and human chorionic gonadotrophin (HCG)-induced granulosa cell cultures. We postulated that the pattern of progesterone secretion may be related to the release of cytokines by ovarian and/or immune cells. To test this, we measured interleukin (IL)-1, IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were increased in natural cycles in women with endometriosis and showed a significant decrease in stimulated cycles in IVF. Also, IL-6 concentrations were increased in the follicular fluid of women with endometriosis and released in higher amounts by granulosa-luteal cells from patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of endometriosis patients. These observations show that the follicular environment is different in cases with endometriosis and suggest that infertility in patients with endometriosis may be related to alterations within the oocyte which, in turn, result in embryos of lower quality, and with a reduced ability to implant.
 ...
PMID:Follicular hormonal environment and embryo quality in women with endometriosis. 1071 31

Several retrospective analyses of IVF and oocyte donation programmes, performed to gain clinical knowledge of the factors implicated in the aetiology of endometriosis-associated infertility, have demonstrated that the quality of the embryo is affected in patients with endometriosis. To understand the mechanisms of this alteration, the endocrine, paracrine and autocrine conditions induced during folliculogenesis in women with and without endometriosis were investigated. The first approach was to study ovarian steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed that the pattern of progesterone secretion may be related to changes in the release of cytokines by ovarian and white blood cells. Hence, a second trial measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were higher in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing significantly in serum from stimulated cycles. In addition, IL-6 concentrations were higher in the follicular fluid of women with endometriosis than in those in the control group and IL-6 was released in higher amounts by granulosa luteal cells of patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of patients with endometriosis. These observations indicate that infertility in patients with endometriosis may be related to alterations within the follicle which, in turn, result in oocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed in the oocyte donation model. These alterations may be induced by functional changes in the process of folliculogenesis that affect steroid synthesis, as well as by cytokine release by ovarian and blood cells.
 ...
PMID:The pathophysiology of endometriosis-associated infertility: follicular environment and embryo quality. 1088 40

The ephemerality of the maturing follicle and subsequent corpus luteum as they perform their gametogenic and/or endocrine functions during the ovarian cycle is associated with remarkable changes in local vasculature. Studies on the angiogenic and angiolytic process in the ovary, rare in healthy adult tissues, complement recent efforts to understand vasculogenesis in embryonic tissues and to control angiogenesis in pathologic states such as cancer. Several reports indicate that the newly discovered vascular-specific angiogenic factors are expressed in the ovary, notably members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families plus their receptors (VEGF-Rs, neuropilins, Tie). Unlike in many other tissues, gonadotropic hormones (particularly luteinizing hormone, [LH]) are major stimulators of angiogenesis and VEGF/Ang expression in the ovary. However, local factors such as insulin-like growth factors or oxygen tension likely modulate the angiogenic processes. Recent studies employing systemic or local administration of anti-angiogenic drugs (TNP-470 or fumagillin) or specific VEGF antagonists (VEGF antibody or soluble VEGFR-1) demonstrate a vital role for normal angiogenesis and VEGF action in follicle development, ovulation, or corpus luteum function. Further studies discerning the various angiogenic factors and their roles in controlling the growth, maturation, function, and regression of the vasculature in ovarian compartments during the menstrual cycle could yield novel strategies for manipulating fertility or for alleviating infertility.
 ...
PMID:Regulation and action of angiogenic factors in the primate ovary. 1175 Jul 32

Endometriosis is one of the most common causes of infertility and chronic pelvic pain and affects 1 in 10 women in the reproductive-age group. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility, and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed the baboon as an appropriate nonhuman primate to study the etiology of this disease. We suggested that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Following inoculation with menstrual endometrial tissues in two consecutive menstrual cycles, baboons develop lesions that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months revealed a preponderance of red raised nodules at the first month, while both red lesions and reddish-blue proliferative endometriotic lesions were evident at 4 and 10 months. The presence of glandular tissue and stromal fibroblasts in these lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed estrogen receptor beta (ERbeta), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor (VEGF) predominantly. However, aromatase expression was only readily evident at 10 months, although some lesions obtained at 4 months expressed low levels of aromatase. Therefore, our preliminary data suggest that endometriosis can be artificially induced in baboons, and the role of exogenous and endogenous estradiol in proliferation, angiogenesis, and immune modulations can now be evaluated in a potentially systemic manner.
 ...
PMID:A modified baboon model for endometriosis. 1194 57

Angiogenesis is a key aspect of the dynamic changes occurring during the normal ovarian cycle. Hyperplasia and hypervascularity of the ovarian theca interna and stroma are also prominent features of the polycystic ovary syndrome (PCOS), a leading cause of infertility. Compelling evidence indicated that vascular endothelial growth factor (VEGF) is a key mediator of the cyclical corpus luteum angiogenesis. However, the nature of the factor(s) that mediate angiogenesis in PCOS is less clearly understood. Endocrine gland-derived (EG)-VEGF has been recently identified as an endothelial cell mitogen with selectivity for the endothelium of steroidogenic glands and is expressed in normal human ovaries. In the present study, we compared the expression of EG-VEGF and VEGF mRNA in a series of 13 human PCOS and 13 normal ovary specimens by in situ hybridization. EG-VEGF expression in normal ovaries is dynamic and generally complementary to VEGF expression in both follicles and corpora lutea. A particularly high expression of EG-VEGF was detected in the Leydig-like hilus cells found in the highly vascularized ovarian hilus. In PCOS ovaries, we found strong expression of EG-VEGF mRNA in theca interna and stroma in most of the specimens examined, thus spatially related to the new blood vessels. In contrast, VEGF mRNA expression was most consistently associated with the granulosa cell layer and sometimes the theca, but rarely with the stroma. These findings indicate that both EG-VEGF and VEGF are expressed in PCOS ovaries, but in different cell types at different stages of differentiation, thus suggesting complementary functions for the two factors in angiogenesis and possibly cyst formation.
 ...
PMID:Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. 1275 45

Overexpression of vascular endothelial growth factor (VEGF) in the testis of transgenic mice induces infertility, suggesting a potential role for VEGF in the process of spermatogenesis. Spermatogenesis occurs within the confines of the seminiferous tubules, and the seminiferous epithelium lining these tubules consists of Sertoli cells and germ cells in various stages of maturation. We investigated the source of VEGF and VEGF-target cells within the seminiferous tubules of the normal mouse testis. Sections of testes fixed in Bouin solution and embedded in paraffin were subjected to immunofluorescent staining with specific antibodies against VEGF, and its receptors, VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1). Total RNA was extracted from isolated populations of Sertoli cells, type A spermatogonia, pachytene spermatocytes, and spermatids. Primer pairs specific for VEGF and its receptors were designed and reverse-transcriptase polymerase chain reaction (RT-PCR) was performed. Immunofluorescent studies indicated that VEGF is strongly expressed in the cytoplasm of Sertoli cells. VEGFR-1 and VEGFR-2 were not expressed by the Sertoli cell. In contrast, a differential expression of VEGF receptors was observed in germ cells. Although VEGFR-2 was expressed in the cytoplasm of type A spermatogonia, VEGFR-1 was expressed in the acrosomal region of spermatids and spermatozoa. Pachytene spermatocytes did not exhibit any staining. Further, we examined the transcription of VEGF and its receptors by RT-PCR. VEGF was actively transcribed only in Sertoli cells. The transcription of VEGFR-2 was confined to type A spermatogonia. Interestingly, VEGFR-1 was transcribed both in pachytene spermatocytes and round spermatids. The mRNA expression of VEGFR-1 and VEGFR-2 in germ cells was inversely correlated during postnatal development of the mouse testis. Thus, VEGF may play a potential role in regulating the initial stages of the process of spermatogonial proliferation through VEGFR-2 and spermiogenesis through VEGFR-1.
 ...
PMID:Expression of vascular endothelial growth factor receptors during male germ cell differentiation in the mouse. 1277 25

Perifollicular angiogenesis is closely associated with ovarian follicular development. To investigate whether additional induction of perifollicular angiogenesis would support subsequent follicular development, we directly injected vascular endothelial growth factor (VEGF) gene fragments into the ovaries of miniature gilts, followed by gonadotroph treatment to stimulate follicle growth. In addition, to confirm extraexpression of the VEGF gene after injection, we assessed the expression of two isoforms of VEGF (VEGF 120 and VEGF 164) in granulosa cells and expression of fms-like tyrosine kinase (Flt-1), expression of fetal liver kinase (Flk-1), and density of capillary networks in theca cells. Direct injection of VEGF gene fragments into the ovaries was performed 7 days before eCG treatment. The ovaries in miniature gilts were removed 72 h after eCG treatment for histological examination. Granulosa cells and thecal tissues in the antral follicles (diameter, >4 mm) were collected to detect the mRNA expression of VEGF isoforms in the granulosa cells and of Flt-1 and Flk-1 in the thecal tissues by semiquantitative reverse transcription-polymerase chain reaction. The VEGF levels were measured in the follicular fluid by enzyme immunoassay. Injection of VEGF gene fragments increased the level of mRNA expression of VEGF 120 and 164 isoforms in the granulosa cells and VEGF protein contents in the follicular fluid. The number of preovulatory follicles and the capillary density in the theca interna increased significantly in the ovaries injected with VEGF gene fragments compared with those treated with eCG alone. The Flt-1, but not the Flk-1, mRNA expression show a tendency toward increasing in the thecal tissues of antral follicles in the ovaries injected with VEGF gene fragments. These results demonstrate that Flt-1 may be predominantly involved in the regulation of the capillary network in the theca interna during follicular development. Our data suggest that the regulation of perifollicular angiogenesis during follicular development is a very important factor in the development of ovulatory follicles. Our findings may offer an innovative technique for enhanced induction of follicular development in the ovary through gene and hormonal treatment, which may lead to prevention of infertility caused by ovarian dysfunction.
 ...
PMID:Induction of follicular development by direct single injection of vascular endothelial growth factor gene fragments into the ovary of miniature gilts. 1282 86

Postoperative peritoneal adhesions are common and serious complications of general abdominal and gynecological surgery that can lead to chronic abdominal pain, small-bowel obstruction and infertility. The specific pathophysiology of peritoneal adhesions remains elusive and current treatment is relegated to prevention through meticulous surgical technique and protective physical barriers, gels and solutions. We have reported that reactive oxygen species (ROS), generated by phagocytic cells at the site of tissue injury, serve as major signaling molecules regulating the expression of vascular endothelial growth factor (VEGF) and subsequent wound repair. We hypothesized that peritoneal adhesions are a product of over-healing surgical wounds and that, like in wound healing, ROS are implicated in their pathogenesis. We examined the presence of footprints of ROS and the ROS-inducible angiogenic factor VEGF in human adhesion tissue. An experimental model of peritoneal adhesion was established in rodents to study of the dynamics of ROS-induced gene expression during de novo adhesion tissue formation. Immunohistochemical analysis demonstrated presence of ROS/oxidant and macrophages in human peritoneal tissue. The presence of ROS and ROS-sensitive transcription factor EGR-1 was also evident in an experimental rodent peritoneal adhesion model. Along with ROS, VEGF, and a large number of mature and immature CD31/vWF positive blood vessels were present in the adhesion tissue. These observations are not consistent with the contention that adhesions are non-functional scar tissue. The newly developed rodent model of adhesion may present a useful approach to reproducibly and objectively study molecular mechanisms underlying the dynamic process of de novo adhesion tissue formation.
 ...
PMID:Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesions. 1496 Nov 85


1 2 3 4 5 6 Next >>