Clinical Benefits of Decreased Photo-Oxidative Stress on Human Embryo Development.

OBJECTIVE: Early embryonic development is characterized by rapid cell division and gene activation, making the embryo extremely sensitive to environmental influences. Light exposure can affect embryonic development through a direct toxic effect on the embryo via the generation of reactive oxygen species. In a previous study, we demonstrated the positive effect of improved light-protected embryo culture conditions implemented in our laboratory. This study aimed to investigate the changes in human embryo development under light protection during the conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: We tested the potential beneficial effect of light filters to reduce the risk of toxic effects of light. IVF outcomes were compared between two experimental conditions, light protection with red light filters versus no light protection as a control. RESULTS: Blastocyst development rate in IVF was significantly higher in the light-protected group than in the group treated under conventional conditions (46.6 vs. 26.7%). In the case of ICSI, we obtained a similar result (44.5 vs. 31.6%). The rate of cryopreservation with at least one embryo was higher in the light-protected phase (32.8%) than in the conventionally manipulated phase (26.8%). The abortion rate was also significantly lower during the light-protected period in IVF, resulting in a higher live birth rate. CONCLUSIONS: The implementation of light protection to reduce the embryotoxic wavelengths of light in IVF centers may improve the blastocyst development rate and embryo quality while maintaining embryo safety.

Thrombocytes and Platelet-Rich Plasma as Modulators of Reproduction and Fertility.

Thrombocytes play an essential role in hemostasis and thrombosis. Moreover, the controlled activation of thrombocytes is required in reproduction and fertility. The platelet-activating factor and the controlled activation of platelets have important roles in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets accumulate in the follicular vessels surrounding the follicle and, due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters), locally increase oocyte maturation and hormone secretion. Furthermore, activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Low-dose aspirin can prevent OHSS during ovulation induction, while intrauterine or intraovarian administration of platelet-rich plasma (PRP) increases the endometrium thickness and receptivity as well as oocyte maturation. Activated thrombocytes rapidly release the contents of intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of thrombocytes, it is reasonable to suppose a platelet-associated regulatory system (PARS) in reproduction. Although we are far from a complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilization are promising.

Oxidative Stress in Assisted Reproductive Techniques, with a Focus on an Underestimated Risk Factor.

Based on current findings, the presence of oxidative stress has a significant impact on the quality of gametes and embryos when performing assisted reproductive techniques (ART). Unfortunately, in vitro manipulation of these cells exposes them to a higher level of reactive oxygen species (ROS). The primary goal of this review is to provide a comprehensive overview of the development of oxidative stress in female and male reproductive systems, as well as in the case of the pre-implantation embryo and its environment. This review also focuses on the origins of ROS and the mechanisms of oxidative stress-induced damage during ART procedures. A well-known but underestimated hazard, light exposure-related photo-oxidation, is particularly concerning. The effect of oxidative stress on ART outcomes, as well as the various strategies for preventing it, are also discussed. We emphasize the role and significance of antioxidants and light protection including forms, functions, and mechanisms in the development of gametes and embryos in vivo and in vitro.

The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.

Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.

Prenatal dance activity enhances foetal and postnatal cognitive and motor development.

Introduction: No research has examined the impact of any physical-artistic-cognitive activity on foetal neurodevelopment. The aim of the study was to investigate the efficacy of a unique prenatal dance activity in pre- and postnatal cognitive and motor development as a complementary health care practice. Methods: 26 clinically uncomplicated primiparas and multiparas with singleton pregnancies and their later born children were examined in this prospective study at the University of Pécs, Hungary. The activity group participated in supervised, 60-min, twice-weekly, moderate-intensity prenatal dance classes for 19.56 ± 3.97 weeks, whereas the control group did not. We determined the developmental ages of their children with the Bayley Scales of Infant and Toddler Development in both groups at 5 weeks of age and in the activity group at 33 months of age. Results: Prenatal dance activity did not cause any adverse outcomes. Infants in the activity group had significantly higher mean developmental ages than the control group regarding cognitive skills (P < 0.001), receptive (P < 0.001) and expressive communication (P = 0.007), fine (P < 0.001) and gross motor (P = 0.001). As toddlers their mean developmental ages were significantly higher than their mean calendar age regarding cognitive skills (P = 0.001), receptive (P = 0.001) and expressive communication (P = 0.001), fine (P = 0.002) and gross motor (P = 0.001). Conclusions: Our results confirm the safe implementation of this prenatal dance activity and the more advanced cognitive and motor development of children in the activity group as infants compared to the control group and as toddlers compared to the norm. These results offer a novel approach to dance in pre- and postnatal clinical practice.

The role of platelets in reproduction / A thrombocyták szerepe a reprodukcióban

It is well known that platelets play a major role in hemostasis and thrombosis. Beyond these classic functions, the controlled activation of platelets is required in reproduction and immune response. In this review, we attempt to summarize the most important roles of thrombocytes in reproduction. The most recent studies of thrombocyte research provide remarkable insights into the physiological and clinical importance of this cellular fragment. We have summarized the key findings we have taken from the relevant literature ­ including our previous publications ­ and emphasized their significance. The plateletactivating factor and the controlled activation of platelets have important role in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Lowdose aspirin can prevent OHSS during ovulation induction, while intrauterine infusion of plateletrich plasma (PRP) increases the endometrium thickness and receptivity. Activated platelets rapidly release the contents of preformed intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of platelets, it is reasonable to suppose a plateletassociated regulatory system (PARS) in reproduction. Several studies prove the importance of thrombocytes in various essential physiological processes including reproduction. Although we are far from the complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilisation are promising.

Tissue Sodium Accumulation: Pathophysiology and Clinical Implications.

Excessive sodium intake has been well established as a risk factor for the development and progression of cardiovascular and renal diseases. Its adverse effects are achieved by renal sodium retention and related volume expansion and by inducing low-grade inflammation and oxidative stress (OS) in the target tissues. This review presents the recent concept of nonosmotic sodium storage in the skin interstitium, the subsequent dissociation of sodium and volume homeostasis, and the cellular response to the increased tissue sodium concentration. Furthermore, data are shown on the sodium barrier and buffering potential of the endothelial glycocalyx that may protect the functional integrity of the endothelium when it is challenged by an increased sodium load. Finally, examples will be given of the involvement of oxygen free radicals (OFR) in sodium-induced tissue damage, and some clinical entities will be mentioned that are causally associated with sodium/volume retention and OS.

Key to Life: Physiological Role and Clinical Implications of Progesterone.

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means "promoting gestation", this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.

Measurement of Food Losses in a Hungarian Dairy Processing Plant.

The phenomenon of food waste and food loss at any stage of the supply chain is significant in developed economies. The purpose of this article is to highlight the areas of milk processing where milk loss occurs, and, after quantifying the data obtained, reveal the extent of the losses. To achieve the goals, we conducted on-site visits to one of Hungary's milk processors. The methodology is based on the Food Loss and Waste (FLW) standard, accordingly we determined the extent of milk loss at the company level, supplemented with loss values by each dairy product. During the analyzed processing stages (receiving of raw milk, skimming, pasteurization, Extended Shelf-Life (ESL) milk, cheese milk, sour cream, yoghurt, and kefir) 1203.4-1406.8 L of raw material per day can be accounted as losses, which makes up 0.9-1% of daily production. A Milk Production-Milk Losses (MPML) model was created where six factors (technology and automation, design of the plant aspects, quantity of orders, expertise of employees, number of product variants, optimal storage capacity) were methodized that significantly influence the rate of milk losses over different time periods. Our paper highlights how areas of the production stage can be developed to decrease milk loss.

How to Reduce the Potential Harmful Effects of Light on Blastocyst Development during IVF.

PURPOSE: Earlier findings revealed the damaging effect of visible light on zygotes and gametes. The aim of our study is to eliminate or significantly reduce the potentially harmful effects of light exposure during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and to investigate the effect of light protection on embryo development and implantation. MATERIALS AND METHODS: To protect sperm cells, oocytes, and embryos from the potential harmful effects of light exposure during laboratory procedures, we created a dark environment for the cells and applied red filters on laboratory lamps and UV or infrared filters in the microscopes in order to eliminate white light exposure of the cells throughout all work stages. RESULTS: The fertilization rate was significantly (p = 0.011) higher in light-protected ICSI cycles. Blastocyst development rates (blastocyst/embryo) were significantly (p < 0.001) higher in light-protected embryos than in those manipulated in conventional light conditions both in IVF (20.9% difference) and ICSI (38.6% difference). Numbers of clinical pregnancies/transfers of ICSI fertilized day 5 blastocysts were also significantly (p = 0.040) higher in light-protected conditions. CONCLUSIONS: These data show that light protection has a positive effect on fertilization rate and increases the blastocyst development as well as the number of clinical pregnancies/transfers. Implementation of this light protection method in IVF centers may improve the success rate while maintaining maximal embryo safety.

Disturbance of taste reactivity and other behavioral alterations after bilateral interleukin-1ß microinjection into the cingulate cortex of the rat.

The anterior cingulate cortex (ACC), is known to be intimately involved in food-related motivational processes and their behavioral organization, primarily by evaluating hedonic properties of the relevant stimuli. In the present study, the involvement of cingulate cortical interleukin-1ß (IL-1ß) mediated mechanisms in a) gustation associated facial and somato-motor behavioral patterns of Wistar rats were examined in taste reactivity test (TR). In addition, b) conditioned taste aversion (CTA) paradigm was performed to investigate the role of these cytokine mechanisms in taste sensation associated learning processes, c) the general locomotor activity of the animals was observed in open field test (OPF), and d) the potentially negative reinforcing effect of IL-1ß was examined in conditioned place preference test (CPP). During the TR test, species specific behavioral patterns in response to the five basic tastes were analyzed. Response rates of ingestive and aversive patterns of the cytokine treated and the control groups differed significantly in case of the weaker bitter (QHCl, 0.03 mM), and the stronger umami (MSG, 0.5 M) tastes. IL-1ß itself did not elicit CTA, it did not interfere with the acquisition of LiCl induced CTA, and it also failed to cause place preference or aversion in the CPP test. In the OPF paradigm, however, significant differences were found between the cytokine treated and the control groups in the rearing and grooming, the number of crossings, and in the distance moved. Our results indicate the involvement of cingulate cortical IL-1ß mechanisms in the control of taste perception and other relevant behavioral processes.

Follicular fluid progesterone concentration is associated with fertilization outcome after IVF: a systematic review and meta-analysis.

Follicular fluid is a key biochemical environment for oocyte development. The potential effect of follicular progesterone level on successful fertilization is a subject of debate, and so the aim of this study was to provide a summary of the currently available evidence on the association between follicular fluid progesterone level and fertilization outcome. To do so, a systematic review and a meta-analysis were performed, with the literature searches being conducted in three databases (PubMed, Embase and the Cochrane Library) to identify all relevant studies published up to 19 August 2017. Data were available from 13 studies (four intracytoplasmic sperm injection [ICSI] and nine conventional IVF) and 1009 individually aspirated follicular fluid samples were included in the analysis. The progesterone levels in follicular fluid were significantly higher in normal fertilization than in failed fertilization, both in conventional IVF (33% difference, P < 0.001) and ICSI (34% difference, P = 0.004). Although these data show that fertilized oocytes are derived from follicles with higher levels of progesterone, the results must be interpreted with caution, because of various progesterone measurement methods and different treatment protocols and it is too early to state that follicular fluid progesterone level could be considered as a marker for oocyte quality.

The effect of loss of the glucose-monitoring neurons in the anterior cingulate cortex: Physiologic challenges induce complex feeding-metabolic alterations after local streptozotocin microinjection in rats.

The anterior cingulate cortex (ACC) is interrelated to limbic structures, parts of the central glucose-monitoring (GM) network. GM neurons, postulated to exist here, are hypothesised to participate in regulatory functions, such as the central control of feeding and metabolism. In the present experiments, GM neurons were identified and examined in the ACC by means of the multibarreled microelectrophoretic technique. After bilateral ACC microinjection of streptozotocin (STZ), glucose tolerance tests (GTTs), and determination of relevant plasma metabolite concentrations were performed. Body weights were measured at regular time points during the GTT experiment. Ten percent of the neurons - 30 of 282 recorded cells - responded to the administration of D-glucose, thus, declared to be the GM units. The peak values and dynamics of the GTT blood glucose curves, the plasma metabolite concentrations, and the weight gain were pathologically altered in the STZ treated animals. Our recording experiments revealed the existence of GM neurons in the anterior cingulate cortex. STZ induced selective destruction of these chemosensory cells resulted in feeding and metabolic alterations. The present findings indicate distinguished significance of the cingulate cortical GM neurons in adaptive processes of maintenance of the homeostatic balance.

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance.

[Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis]. / A medialis ventrolateralis praefrontalis (orbitofrontalis) kéreg glükózmonitorozó idegsejtjei szerepet játszanak a homeosztázis fenntartásában.

INTRODUCTION: The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. AIM: The functional significance of these chemosensory neurons was to be elucidated. METHOD: Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. RESULTS: Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. CONCLUSIONS: Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors.

Taste reactivity alterations after streptozotocin microinjection into the mediodorsal prefrontal cortex.

The mediodorsal prefrontal cortex (mdPFC), as an integrant part of the forebrain glucose-monitoring neural network, plays important roles in neural control of feeding. Previous studies suggested that streptozotocin (STZ) causes selective destruction of forebrain glucose-monitoring (GM) neurons leading to development of feeding disturbances. The goal of this research was to evaluate gustatory consequences of bilateral streptozotocin microinjection into the mediodorsal prefrontal cortex of male Wistar rats during conditioned taste avoidance (CTA) acquisition, as well as during taste reactivity tests. Bilateral streptozotocin microinjection failed to impair CTA learning, tested in a saccharin CTA paradigm. However, taste reactivity deficit was found by a modified version of the protocol introduced by Grill and Norgren. The streptozotocin treated animals displayed significantly poorer ingestive reactions to pleasant taste stimuli than did rats of the control group. The unpleasant taste stimuli elicited ingestive and rejective taste reactivity patterns in a comparable manner in rats of the STZ vs. vehicle microinjected groups. The glucose-monitoring neurons of the mdPFC and their distinct role in the gustatory perception may have particular significance in the adaptive control of feeding.

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control.

Homeostatic alterations after IL-1beta microinjection into the nucleus accumbens of the rat.

The present study investigates the effects of direct administration of interleukin-1beta (IL-1beta) into the nucleus accumbens (NAcc) on homeostatic regulation. Short- and long-term food intakes (FI), water intakes (WI) and body temperature (BT) were measured before and after bilateral microinjection of IL-1beta (with or without paracetamol pretreatment) into the NAcc of Wistar rats, and the effects were compared with those found in vehicle treated control animals. In addition, blood glucose levels, along with a glucose tolerance test (GTT), and plasma concentrations of metabolic parameters, such as total cholesterol, triglycerides, HDL, LDL and uric acid were determined in cytokine treated and control rats. Short-term FI and WI were suppressed after intraaccumbens application of IL-1beta. A significant increase of BT was also observed after the cytokine microinjection. Pretreatment with paracetamol failed to influence the anorexigenic, adipsogenic, and pyrogenic effects of IL-1beta. A definite glucose intolerance of the cytokine treated animals and their pathologically elevated blood glucose levels became obvious in the acute GTT. Following IL-1beta microinjection, plasma levels of triglycerides, total cholesterol and LDL were found increased. Our present findings show that the NAcc is an important site of action of IL-1beta mediated processes in central homeostatic regulation.