Brain derived neurotrophic factor circulating levels in patients undergoing IVF (original) (raw)
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Fertility and Sterility, 2008
Objective: To determine follicular-fluid neurotrophin levels in women undergoing assisted reproductive techniques for different etiologies of infertility. Design: Prospective observational study. Setting: Academically affiliated assisted reproductive techniques unit. Patient(s): One hundred six patients undergoing an IVF cycle for different etiologies of infertility. Intervention(s): Assessment of follicular fluid for neurotrophins. Main Outcome Measure(s): Follicular-fluid neurotrophin concentrations.
Journal of International Medical Research, 2019
Objective This study aimed to examine the effect of interactions between serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and kisspeptin on the reproductive potential in women receiving in vitro fertilization (IVF). Methods Paired serum and follicular fluid (FF) samples were obtained from 30 consecutive patients receiving IVF. Primary and secondary outcome measures were the rate of chemical/clinical pregnancy and the number of mature oocytes and embryos, respectively. Serum and FF 5-HT, BDNF, kisspeptin, and platelet-activating factor (PAF) levels were measured by enzyme-linked immunosorbent assay. Results In response to ovarian hyperstimulation, serum 5-HT and kisspeptin levels significantly increased, whereas serum BDNF and PAF levels remained unchanged. These factors were detected in FF, but they were unrelated to serum levels. FF 5-HT and BDNF levels were positively correlated. Serum kisspeptin levels were negatively correlated with FF BDNF and serum and FF PAF levels...
Brain-Derived Neurotrophic Factor: A Novel Human Ovarian Follicular Protein
The Journal of Clinical Endocrinology and Metabolism, 2002
Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their roles in the mammalian nervous system. One such neurotrophin, brain-derived neurotrophic factor (BDNF) was originally described in the nervous system but has now been shown to be expressed in a variety of nonneuronal tissues including endocrine tissues. We examined the human ovarian follicle for its possible secretion of BDNF and further studied mouse oocytes to determine BDNF's possible influence upon oocyte maturation. In a series of experiments derived from human specimens from in vitro fertilization following oocyte retrieval, BDNF was detected in human follicular fluid. To define the source of BDNF, cumulus granulosa cells (the cells that immediately surround the developing oocyte) were grown in cell culture for 1-2 d. BDNF protein increased over 24 h in the culture medium. Moreover, the release of BDNF was enhanced upon stimulation with cAMP or forskolin, an activator of cAMP. In contrast, mural granulosa (cells lining the follicle), oocytes, and embryos did not release appreciable quantities of BDNF. To examine possible targets of BDNF, mouse studies were used to localize the BDNF receptor, Trk B, immunocytochemically. The receptor was present on the surface of isolated oocytes. Moreover, BDNF promoted mouse oocyte maturation in culture. These experiments demonstrate for the first time the presence and secretion of BDNF from follicular cells in the human ovary and suggest a possible role for BDNF in the regulation and modulation of oocyte maturation.
Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors
Human reproduction (Oxford, England), 2015
Are brain-derived neurotrophic factor (BDNF) and its receptors, NTRK2, NGFR and SORT1, regulated by ovarian steroids in the uterus? BDNF and its low affinity receptor, nerve growth factor receptor (NGFR), are regulated by estradiol in the uterus. Recent studies have revealed a central role for neurotrophins in placental development, endometrial stem cell neurogenesis, endometrial carcinoma and endometriosis. Complex signaling pathways involving BDNF and its receptors are regulated by ovarian hormones in the brain, however their expression and regulation in the uterus is poorly defined. This experimental animal study involved a total of 80 mice. Female C57BL/6 mice (n = 50) were monitored daily for estrous cycle stage, and uterine horns were collected. A second group of mice (n = 30) were ovariectomized and given estradiol, progesterone, estradiol + progesterone, or saline for 4 days. Uterine expression of BDNF and its receptors were quantified by real-time PCR and western blot, and ...
Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor
Human Reproduction, 2007
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity and influences learning, memory and cognitive behaviour. The aim of this study is to assess plasma BDNF variations according to hormonal status. METHODS: A total of 60 subjects were included: 20 fertile ovulatory women, 15 amenorrhoeic women and 25 postmenopausal women. Blood samples were collected after overnight fasting. For 5 out of the 20 fertile women, samples were collected every 2 days throughout the whole menstrual cycle. Following basal evaluation, 10 out of 25 postmenopausal women were administered a hormone replacement therapy (HRT) and reevaluated after 6 months of treatment. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. In fertile women, estradiol (E 2 ), progesterone and gonadotrophins were also assessed. RESULTS: In fertile women, luteal phase levels of plasma BDNF were significantly higher than follicular phase levels (P < 0.001). BDNF increased from early follicular phase up to Day 14 of the cycle, reaching a pre-ovulatory peak, similar to E 2 . A second rise took place during mid-luteal phase, with a peak on Day 24. Amenorrhoeic subjects, as well as postmenopausal women, showed significantly lower plasma BDNF levels compared with fertile females (P < 0.001). BDNF was positively correlated with E 2 and progesterone and negatively correlated with menopausal age. HRT restored BDNF levels to those present in fertile women during the follicular phase. CONCLUSIONS: Plasma BDNF levels are influenced by hormonal status. Modifications in BDNF circulating levels during the menstrual cycle suggest a potential role for gonadal sex hormones (E 2 and progesterone) in regulating neurotrophin expression.
The Journal of Clinical Endocrinology & Metabolism, 2002
Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their role in the mammalian nervous system. We first reported the unique presence of one neurotrophin, brain-derived neurotrophic factor (BDNF), in the follicular fluid of the human ovarian follicle. The BDNF receptor, Trk B, was identified in mouse oocytes, and BDNF accelerated first polar body extrusion in vitro. In the present study, we examined human follicular fluid and mouse immature oocytes to determine whether another Trk B ligand, neurotrophin-4/5 (NT-4/5), is present within the ovarian follicle and if so, whether it demonstrates activity similar to that of BDNF. We also examined whether a non-Trk B neurotrophin ligand, neurotrophin-3 (NT-3), is present within the follicle and has a possible role in oocyte maturation.
Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis
Fertility and Sterility, 2015
To evaluate novel clinical markers of endometriosis including the neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) and compare them to others previously reported in the literature including cancer antigen 125 (CA-125) and C-reactive protein (CRP). Prospective study. University hospital. One hundred thirty-eight women were prospectively and consecutively recruited (April 2011-April 2015; cases: undergoing endometriosis surgery, n = 96; controls: benign gynecological surgery, n = 24 combined with healthy women, no history of pelvic pain, not undergoing surgery, n = 18). Collection of peripheral blood, gynecological and demographic information, eutopic biopsy in women undergoing laparoscopy. Circulating BDNF, NGF, NT4/5, CA-125, and CRP were quantified by ELISA. Plasma concentrations of BDNF were significantly greater in women with endometriosis (1,091.9 pg/mL [640.4-1,683.1]; n = 68, untreated) than in controls (731.4 pg/mL [352.1-1,176.2]; n = 36), whereas circulating NGF, NT4/5, CA-125, and CRP were not different. When assessed for their ability to differentiate between women with revised Classification of the American Society of Reproductive Medicine stage 1 and 2 or stage 3 and 4 disease and controls, BDNF was the only putative marker able to identify stage 1 and 2 disease, with a sensitivity and specificity of 91.7% and 69.4%, respectively, using an arbitrary cutoff value of 1,000 pg/mL. We also demonstrated that circulating BDNF in women with endometriosis who were receiving ovarian suppression for disease was equivalent to that in the control group. This suggests that BDNF may also offer the opportunity to monitor patient response to treatment. Plasma BDNF is a potentially useful clinical marker of endometriosis that is superior to NGF, NT4/5, CA-125, and CRP.
Role of Neurotrophic Factors in Early Ovarian Development
Seminars in Reproductive Medicine, 2009
Much is known about the endocrine hormonal mechanisms controlling ovarian development. More recently, attention has been focused on identifying regulatory pathways that, operating within the ovarian microenvironment, contribute to the acquisition of ovarian reproductive competence. Within this framework, the concept has been developed that neurotrophins (NTs) and their Trk tyrosine kinase receptors, long thought to be exclusively required for the development of the nervous system, are also involved in the control of ovarian maturation. The ovary of several species, including rodents, sheep, cows, nonhuman primates and humans, produce NTs and express both the high-affinity receptors and the common p75 NTR receptor required for signaling. Studies in humans and rodents have shown that this expression is initiated during fetal life, before the formation of primordial follicles. Gene targeting approaches have identified trkB, the highaffinity receptor for neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF), as a signaling module required for follicular assembly, early follicular growth and oocyte survival. A similar approach has shown that nerve growth factor (NGF) contributes independently to the growth of primordial follicles into gonadotropin-responsive structures. Altogether, these observations indicate that NTs are important contributors to the gonadotropin-independent process underlying the formation and initiation of ovarian follicular growth.
Reproduction, 2005
The ability of an oocyte to support early embryonic development requires both nuclear and cytoplasmic maturation. We have investigated the effects of brain-derived neurotrophic factor (BDNF) on maturation of the bovine oocyte and embryo development after parthenogenetic activation. By RT-PCR and immunohistochemistry, cumulus and oocytes were shown to express mRNA and protein for BDNF and the p75 common neurotrophin receptor. However, mRNA for the BDNF-specific full length and truncated isoforms of the TrkB receptor are only detected in cumulus, suggesting that oocytes and cumulus differ in their capacity to respond to neurotrophin signalling. In in vitro maturation experiments, the proportion of cumulus oocyte complexes maturing to metaphase II was not altered by BDNF in groups lacking fetal calf serum (FCS), but was significantly lower than the positive control containing 10% FCS (P < 0.01). However, after maturation, the proportion of parthenogenetically activated oocytes forming blastocysts was highest for 10 ng/ml BDNF (24%, n 5 95) followed by 100 ng/ml BDNF (18%, n 5 91) and 10% FCS (15%, n 5 103), which in turn were greater than no serum (10%, n 5 83; P < 0.01). Maturation in the presence of a BDNF blocking antibody resulted in a blastocyst yield that was comparable to the absence of serum, and lower than in the presence of BDNF (P < 0.01). Similar effects on progression to metaphase II and blastocyst formation were observed using oocytes matured without cumulus. Together, these results provide the first evidence for a role for neurotrophins in promoting oocyte cytoplasmic competence to support embryonic development, despite being insufficient in the absence of serum to enhance nuclear maturation. Reproduction (2005) 129 423-434 q 2005 Society for Reproduction and Fertility