Oxytocin Release Research Articles

Human-animal relationship in water buffalo: quality of stockpeople interactions and their effect on dairy and meat production

Human-animal relationships for livestock refer to the interaction between stockpeople and animals during different stages of the productive cycle. For dairy buffaloes, the interaction during milking requires proper tactile stimulation to promote oxytocin release and prevent stressful handling that might reduce milk ejection. For buffaloes used for meat production, events such as mobilization and transport need to be performed by trained personnel to avoid injuries and negative behavioral responses from the animals. Maintaining a positive human-animal relationship is not only important from an economic perspective, but it is important to improve the welfare of water buffalo.

Biological marker of withdrawal ruptures: Dyadic pattern of incongruence in oxytocin release.

Despite widespread clinical, theoretical, and empirical support for the importance of alliance ruptures, little is known about the underlying biological level at times of rupture. The overarching goal of the present study was to investigate dyadic patterns of in-session oxytocin (OT) change between patients and therapists (e.g., patient's OT increases more than therapist's OT) as markers of withdrawal ruptures. Hypothesis 1 construed that OT incongruence (e.g., larger patient increase in OT in comparison to their therapist OT increase) will mark the occurrence of withdrawal ruptures. Hypothesis 2 construed that this effect of OT incongruence will be more pronounced when anxious attachment orientation is low. Surface analysis was conducted on 628 saliva samples that were gathered before and after therapeutic sessions of 53 patient-therapist dyads enrolled in a randomized control trial treating major depression. Only Hypothesis 2 received empirical support, meaning it was only when anxious attachment orientation was low that there were significantly more withdrawal ruptures when the patient's OT increase was higher than their therapist's OT increase. This is consistent with the literature, suggesting that in times of withdrawal ruptures, the patient and therapist are in an incongruent state. Findings suggest that this incongruence is mirrored at the biological level only when anxious attachment orientation is low. Results shed light on what may be happening between patients and therapists on a biological level during a withdrawal rupture. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Allostasis and Resilience from a Neuroendocrine Perspective

Resilience is a term that describes the capacity of coping with and recovering from stress and adversity. In terms of the concept of allostasis, resilience is the ability to appropriately regulate allostasis, efficiently terminate the allostatic response, prevent the occurrence of allostatic load/overload or restore homeostasis. Recently, it has been shown that oxytocin may be involved in this series of stress adaptation systems. We aim to discuss the changes in oxytocin neuron activation, oxytocin release and its actions of stress adaptation in response to internal and external environmental changes, and the regulation of resilience by oxytocin.

The endocrine disruptor DE-79 alters oxytocinergic transmission and sexual behavior expression in male rats

Polybrominated diphenyl ethers (PBDEs), used as flame retardants are persistent organic pollutants exerting important health effects. PBDEs with >5 bromide substitutions were considered less harmful and therefore extensively used commercially. DE-79 was a widely used PBDE mixture of hexa-, hepta-, octa- and nona-brominated compounds that increases vasopressin (AVP) production. AVP and oxytocin (OT) are both produced in neurons of the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei projecting to the neurohypophysis and to brain regions involved in copulatory behavior. OT plays an important role in male copulation. Since DE-79 alters AVP expression in the SON and PVN, it might also modify OT content and alter male sexual behavior. We analyzed if repeated DE-79 exposure of adult male rats affected OT content and OT receptor (OTR) density in the SON, PVN, medial preoptic area (mPOA), ventral tegmental area, nucleus accumbens, and amygdala, and if male copulatory behavior was affected. We show that DE-79 exposure produces a generalized decrease in brain OT immunoreactivity, increases OTR density in all brain regions analyzed but the mPOA, and reduces the ejaculatory threshold after a first ejaculation. The documented ejaculation-induced OT release might participate in this last effect. Thus, one-week DE-79 exposure alters the OT-OTR system and modifies male rat sexual performance. Based on the literature it could be speculated that these effects are related to the putative endocrine disrupting actions of DE-79, ultimately altering brain OT levels and OTR expression that might affect copulation and other important OT-mediated brain functions.

Genetic variability in the oxytocin system is linked to individual differences in cuddliness among human infants

Pleasant touch facilitates social interactions, affiliative behavior and emotional bonding, contributing to positive infant and child development. Oxytocin is presumed to play an important role in mediating these effects of pleasant touch on brain, body and behavior. However, little is known about the role the oxytocin system plays in pleasant touch during infancy. This study examined the hypothesis that genetic variability in the oxytocin system is linked to individual differences in infants’ cuddliness operationalized as parent-reported behaviors indexing an infant’s motivation to seek out and enjoy caregiver touch. Our results (N = 82) show that a polymorphism in CD38 (rs3796863), previously linked with increased release of oxytocin in adults, was associated with higher reported rates of cuddliness. In contrast, infants with CD38 genotype previously linked to autism spectrum disorder (ASD) and reduced release of oxytocin in adults, was associated with lower rates of cuddliness. These findings support the hypothesis that, from early in human ontogeny, genetic variation in the oxytocin system is systematically linked to individual differences in the reported motivation to seek out, and the enjoyment of receiving, pleasant caregiver touch. This provides novel insights into the neurohormonal processes involved in pleasant touch.

FRI003 Oxytocin Response To Feeding Predicts Reward-driven Calorie Consumption In Adults With Obesity

Abstract Disclosure: R. Boutin: None. M. Wronski: None. A. Aulinas Maso: None. M. Muhammed: None. F. Galbiati: None. L. Kerem: None. S. Carter: None. H. Nazarloo: None. J.M. Davis: None. K. Holman: None. J. Gydus: None. S. Smith: None. E. Asanza: None. F. Plessow: None. E.A. Lawson: Consulting Fee; Self; OXT Therapeutics. Stock Owner; Self; OXT Therapeutics. Objectives: Oxytocin (OXT) is a hypothalamic peptide hormone that reduces reward-related food intake and is under investigation as a potential weight loss therapy. Activation of OXT neurons in appetite pathways results in suppression of posterior pituitary release of OXT to the circulation, such that peripheral OXT levels (in response to feeding) may reflect the opposite of central OXT activity. While a relationship between peripheral OXT response to feeding and appetite has been reported in healthy females, there are no data related to OXT levels and appetite or eating behavior in individuals with obesity. We hypothesized that in individuals with obesity, higher OXT levels in response to feeding would be associated with greater reward-driven food intake assessed during a Cookie Taste Test. Methods: In a cross-sectional study of 53 adults with obesity (56% females; age [mean±SD] 33.7±6.2 years; BMI 36.9±4.9 kg/m2), participants presented after an overnight fast and were provided with a standard 400 kcal mixed meal. We sampled blood before and 30, 60 and 120 minutes after the meal for OXT levels and calculated area under the curve (AUC) as an integrated measure of OXT response to feeding. After receiving a subsequent snack, subjects ate as many cookies as needed to rate the cookies on various characteristics (i.e. sweetness, texture, delectability). We logarithmically transformed non-normal data to achieve a normalized distribution and used Pearson correlation to evaluate the relationship between OXT AUC and number of calories eaten during the Cookie Taste Test (behavioral marker of reward-related eating). Results: OXT AUC in response to a standardized meal predicted subsequent calories consumed at the Cookie Taste Test (R=0.30, p=0.036), such that those with higher OXT levels consumed more calories. Conclusions: Consistent with our hypothesis, peripheral OXT response to a standardized meal predicted subsequent reward-driven caloric intake in adults with obesity. These data suggest that endogenous OXT is involved in regulation of hedonic eating and supports targeting OXT pathways in the treatment of obesity. Presentation: Friday, June 16, 2023

Early Initiation of Breastfeeding Can Accelerate Uterine Involution in Postpartum Women

<div><table cellspacing="0" cellpadding="0" align="left"><tbody><tr><td align="left" valign="top"><p><em>Maternal Mortality Rate (MMR) in Indonesia is still high with the main causes of pre-eclampsia and postpartum hemorrhage, this occurs due to endometritis, congenital coagulation disorders as well as residual conception products, subinvolution of blood vessels at placental implantation. Therefore, efforts are needed to increase uterine contractions in the first minute after birth by stimulating the release of the hormone oxytocin so that the uterus contracts adequately with early initiation of breastfeeding (EIB). This study aims to determine the effect of EIB on uterine involution in postpartum mothers in Bengkulu Regency, Bengkulu Province. </em><em>Design</em><em> of research is cross sectional with independent variable of EIB, dependent variable of uterine involution. External variables measured include early mobilization, age and parity. The sample in this study were postpartum mothers on day 7, a total of 54 people selected by purposive sampling. The research site was located in Central Bengkulu Regency, Bengkulu Province. Data were analyzed univariate, bivariate with Mann Whitney and multivariate with ancova. There is an effect of EIB with uterine involution p=0.000. There is no relationship between parity and uterine involution p=0.100. There is a relationship between age and uterine involution p=0.00. There is a relationship between early mobilization and uterine involution p=0.00. EIB is the dominant factor affecting uterine involution in postpartum mothers. EIB is the dominant factor affecting uterine involution. Health care providers should perform EIB within the first hour after the birth of the baby to prevent sub involution in postpartum women</em><em>.</em></p><p><em> </em></p></td></tr></tbody></table></div><strong><em>Keywords: Breastfeeding, Early, Initiation, Involution, Uterine</em></strong>

Neural circuitry for maternal oxytocin release induced by infant cries.

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing1-6. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers7, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.

The role of the oxytocin system in the resilience of patients with breast cancer.

Breast cancer is a grave traumatic experience that can profoundly compromise patients' psychological resilience, impacting their overall quality of life. The oxytocin system represents one of the essential neurobiological bases of psychological resilience and plays a critical role in regulating resilience in response to social or traumatic events during adulthood. Oxytocin, through its direct interaction with peripheral or central oxytocin receptors, has been found to have a significant impact on regulating social behavior. However, the precise mechanism by which the activation of peripheral oxytocin receptors leads to improved social is still not completely comprehended and requires additional research. Its activation can modulate psychological resilience by influencing estrogen and its receptors, the hypothalamic-pituitary-adrenal axis, thyroid function, 5-hydroxytryptamine metabolism levels, and arginine pressure release in breast cancer patients. Various interventions, including psychotherapy and behavioral measures, have been employed to improve the psychological resilience of breast cancer patients. The potential effectiveness of such interventions may be underpinned by their ability to modulate oxytocin release levels. This review provides an overview of the oxytocin system and resilience in breast cancer patients and identifies possible future research directions and interventions.

Variability inthe expression andperception ofpositive affect inhuman infancy.

Positive emotions play a critical role in guiding human behavior and social interactions. This study examined whether and how genetic variability in the oxytocin system is linked to individual differences in expressing positive affect in human infants. Our results show that genetic variation in CD38 (rs3796863), previously linked to increased release of oxytocin, was associated with higher rates of positive affective displays among a sample of 7-month-old infants, using established parent-report measures. Moreover, infants displaying increased levels of positive affect (smiling and laughter) also showed enhanced brain responses in the right inferior frontal cortex, a brain region previously linked to perception-action coupling, when viewing others smile at them. These findings suggest that, from early in development, genetic variation in the oxytocin system is associated with individual differences in expressed positive affect, which in turn are linked to differences in perceiving positive affect. This helps uncover the neurobiological processes accounting for variability in the expression and perception of positive affect in infancy.

Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling

ABSTRACT Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We find that L. reuteri facilitates oxytocin secretion from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion by L. reuteri is dependent on the gut hormone secretin, which is produced in enteroendocrine cells, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated by L. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.

СИМУЛАЦИОННИ МОДЕЛИ НА ТЕХНОЛОГИЧНИТЕ ОПЕРАЦИИ ПРИ МАШИННО ДОЕНЕ В ДОИЛНИ ЗАЛИ ПАРАЛЕЛ

The hourly productivity of the milking parlour is significantly influenced by the organization of the technological process. Milkers perform a series of sequential operations (entry on the platforms, washing, drying, placing the milking units, removing them, disinfecting the teats, exiting the platforms of the milking parlour) the duration of which is a large part of the total milking time. The duration of the latent period from the release of oxytocin to its contact with the myoepithelial cells in the glandular part of the udder is from 30 s to 90 s (average 60 s). In this line of thought, the following questions arise: "in what time interval should the preparatory operations for milking be performed and what is their permissible duration". The aim of the present study is to develop methodologies (models) for simulating the work of milkers in "Parallel" type parlours. It was found that under the initially set working conditions of only two milkers in the milking parlour, all developed models are applicable for capacities up to 2x8. Models II, III and IV are unacceptable for capacities above 2x8, as the total duration of preparation of milking cows exceeds the time frame by between 30-80%. This finding proves that for a capacity over 2x8 it is necessary to perform technological operations with a larger number of milkers.

Flaxseed can Prevent Adverse Effects of Toluene on Human Ovarian Cell Functions

Background: The aim of our study was to investigate the mechanisms of oil-related product toluene and functional food flaxseed Linum usitatissimum L. on ovaries in humans and the potential protective effect of flaxseed against adverse toluene action. We examined 1) the action of toluene (at doses 0, 10, and 100 ng/ml), 2) flaxseed extract (10 μg/ml), and their combination on cultured human ovarian granulosa cells. Methods: Viability, markers of proliferation (accumulation of PCNA) and apoptosis (accumulation of bax), the release of steroid hormones, IGF-I, oxytocin, and prostaglandin F were analyzed by Trypan blue exclusion test, quantitative immunocytochemistry, and EIA/ELISA. Results: Toluene suppressed all analyzed ovarian parameters. Flaxseed stimulated proliferation, progesterone and IGF-I and reduced prostaglandin F output. The presence of flaxseed supported toluene action on cell viability and apoptosis and inverted its effect on proliferation, progesterone, testosterone, and IGF-I release. Conclusion: These observations a) confirm direct inhibitory/toxic action of toluene on ovarian cells, b) demonstrate the ability of flaxseed to affect ovarian cell functions, c) show the ability of flaxseed to prevent some toxic effect of toluene, and d) indicate the that flaxseed could be a biostimulator of human reproduction and protector against the adverse influence of toluene on female reproduction.

Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation

Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD.

Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory.

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.

O-245 Monitoring oxytocin release in vivo during female sexual behavior using a genetically encoded sensor

Abstract Study question To investigate if the release of oxytocin (OT) in the medial prefrontal cortex (mPFC) fluctuates during discrete phases of female sexual behavior. Summary answer Using a highly sensitive OT-specific genetically encoded sensor, we have recorded behavioral phase-specific OT release in mPFC in freely moving mice. What is known already OT has been reported to participate in the regulation of sexual behavior of both male and female mice. OT activated mPFC neurons by increasing their firing activity. Loss of function studies indicated that pharmacological or genetic ablation of OT signaling in mPFC largely disrupts female sociosexual interest in male mice. OT action is indispensable in female sociosexual behavior, however, its release dynamics have never been recorded before due to technical difficulties. We have developed a highly sensitive OT-specific G-protein-coupled receptor activation-based sensor (OT1.0), and recorded intracellular OT release in behaving mice on the millisecond time-scale. Study design, size, duration Eight C57BJ/6N mice were divided into two groups (n = 4 per group). Intracellular viral transduction with OT1.0 or OT1.0mut vectors was administrated to each group. After viral transduction, 3 weeks were waited to allow sufficient viral expression. Participants/materials, setting, methods After anesthetization, AAVs encoding hSyn-OT1.0 or hSyn-OT1.0mut were injected into the left mPFC of adult female wild-type C57BJ/6N mice; Optical fibers were implanted into the mPFC 3 weeks after AAV injection. The animal’s sexual behaviors were recorded and annotated, while a fiber photometry system was used to record fluorescence signals in the mPFC, using a 470-nm laser at 50 μW for OT1.0 or OTmut. Main results and the role of chance To investigate the dynamics of OT release in mPFC during female sexual behavior, we recorded OT1.0 fluorescence in behaving female mice using fiber photometry. In mPFC of female mice, increases in OT1.0 fluorescence were first observed during the sniffing stage (with rise and decay time constants (T1/2) of 0.4 s and 1.4 s, respectively ). After ejaculation of male mice, mPFC OT1.0 signals of the female mice increased significantly with rise and decay time constants (T1/2) of 0.5 s and 1.5 s, respectively. As a negative control, fluctuation of fluorescence was not observed during any phase of sexual behavior in mice expressing OT1.0mut, suggesting the specificity of the signals measured in mice expressing OT1.0. Limitations, reasons for caution The OT dynamics in mPCF during female sexual behaviors are only recorded in mice. Clinical trials and imaging studies are required to substantiate the therapeutic role of OT in human subjects. Wider implications of the findings This study is likely to deepen our understanding of the role of OT in modulating female sociosexual behavior, which provides more evidence suggesting OT’s potential therapeutic potential in treating sexual dysfunctions. Trial registration number not applicable

Application of intranasal oxytocin and affectionate touch reduce subsequent cortisol concentrations in romantic couples: Results from an ecological momentary assessment study

Social interactions and particularly affectionate touch are vital for mental and physical health. Research shows that affectionate touch is associated with release of oxytocin and has calming and stress reducing effects suggesting a regulatory effect of oxytocin on the hypothalamic pituitary adrenal (HPA) axis. Here, we aimed to systematically investigate the effects of repeated intranasal oxytocin administration on salivary cortisol. Furthermore, we focused on the moderating role of couples’ affectionate touch on biopsychological stress outcomes in everyday life. 80 heterosexual romantic couples (N=160 individuals) completed ecologically momentary assessments over five days. Six times per day participants answered smartphone-based questions regarding affectionate touch and momentary stress levels providing concomitant saliva samples for cortisol assessment. Half of the sample was randomly assigned to an instructed positive appraisal task. In a randomized double-blind design, both partners self-administered oxytocin or placebo on five days twice during the early evening. Multilevel analyses showed that oxytocin administration was associated with higher cortisol in the following morning and stronger decreases during the day. Subjectively reported momentary stress was associated with increase of affectionate touch in couples. Moreover, results indicate that participants, who received affectionate touch from their partner showed significantly lower cortisol levels after oxytocin administration. These results suggest that oxytocin administration paired with affectionate touch in romantic couples can influence HPA axis regulation as indicated via diurnal cortisol levels. Thereby, the data shed light on the neuroendocrine underpinnings of the health-promoting effects of intimate social relationships.

Can flaxseed, chia or puncture vine affect mare ovarian cell functions and prevent the toxic effect of the environmental contaminant toluene?

The aim of this in vitro study was to examine the potential effect of functional food plant extracts, namely, extracts of flaxseed (Linum usitatissimum L.), chia (Salvia hispanica) and puncture vine (Tribulus terrestris L.), on basic mare ovarian cell functions and their response to the environmental contaminant toluene. Mare granulosa cells were incubated with and without toluene (0, 0.02, 0.2 or 2.0 μg/mL) in the presence or absence of flaxseed, chia and puncture vine extracts (10 μg/mL). Markers of cell proliferation (accumulation of proliferating cell nuclear antigen, PCNA) and apoptosis (accumulation of bax), viability (Trypan blue extrusion) and the release of progesterone (P), oxytocin (OT) and prostaglandin F 2 alpha (PGF) were measured. Toluene reduced all other measured parameters except OT release. All the tested plants were able to reduce cell viability and the release of P and PGF, but they did not influence other indexes. Moreover, flaxseed mitigated toluene action on ovarian cell proliferation, apoptosis, OT and PGF, whilst puncture vine prevented and inverted toluene action on P and PGF ourput. Chia extract did not modify toluene action on any parameter. On the other hand, toluene was able to promote the inhibitory action of flaxseed on cell viability and P release and to prevent the inhibitory action of all the plant extracts on PGF release.The present study (1) is the first demonstration, that flaxseed, chia and puncture vine can directly suppress mare ovarian cell functions, (2) shows that toluene can suppress basic ovarian cell functions and modify the reproductive effect of food plants and (3) demonstrates the ability of flaxseed and puncture vine, but not of chia, to prevent some toxic effect of toluene on mare ovarian cell functions.

MicroRNA miR-152 can support ovarian granulosa cell functions and modify apigenin actions

The study aimed to evaluate the involvement of apigenin, microRNA (miR)-152, and their interrelationships in the control of basic ovarian granulosa cell functions. The effects of apigenin (0, 10, and 100 µg/mL), miR-152 analogues or miR-152 inhibitor, and their combinations with apigenin on porcine granulosa cells were examined. Expression levels of miR-152, viability, proliferation, apoptosis, steroid hormones, IGF-I, oxytocin, and prostaglandin E2 release were analyzed. Apigenin increased the expression of miR-152, cell proliferation, and estradiol release and reduced apoptosis, progesterone, and IGF-I output. MicroRNA-152 analogues promoted cell viability and proliferation, as well as the release of progesterone, IGF-I, oxytocin, and prostaglandin E2; however, it inhibited apoptosis and estradiol output. miR-152 inhibitor had the opposite effect. Moreover, miR-152 analogues suppressed the effect of apigenin on cell apoptosis and estradiol release. These observations 1) confirm the involvement of apigenin in the control of basic ovarian cell functions; 2) are the first demonstration of importance of miR-152 in the control of these functions; 3) show the ability of apigenin to promote miR-152 expression and the ability of miR-152 to modify apigenin effects on ovarian cells.

Effects of embryo flushing on serum progesterone levels and the inter-ovulatory period in Arabian donor mares

To obtain the maximum number of cycles throughout the breeding season, avoid unwanted pregnancies and possible endometritis, the luteal phase of donor mares is shortened after embryo flushing. This is achieved by treating the donor with prostaglandin F2α (PGF2α) to destroy the corpus luteum and hence shorten the inter-ovulatory interval (IOI). It has been suggested that manipulation of the cervix and/or uterus during embryo flushing may result in release of endogenous of PGF2α and/or oxytocin, resulting in altered luteal function with a consequent decrease in progesterone and shortening of the cycle. Conversely, other authors have proposed no change in or extension of cycle length following embryo flushing. The purpose of this study was to evaluate the effects of embryo flushing with or without administration of PGF2α on serum progesterone levels and inter-ovulatory interval (IOI). Over two breeding seasons, 26 cycles of 6 Arabian donor mares, aged 4-15 years were studied. Inseminated mares were flushed on Day 8 or 9 post ovulation using Ringer's Lactate and a standard closed embryo flushing technique. After flushing the mares were divided into 2 groups; Group 1 (n=9) were treated with dl-Cloprostenol and Group 2 (n=17) were untreated. Blood wascollected on the day of embryo flushing and 48h later and the serum frozen until analysis using a progesterone ELISA kit (DRG Instruments, Marburg, Germany). For statistical analysis, a Shapiro-Wilks normality test was performed before 2-way ANOVA, followed by Tukey's post hoc and unpaired T tests. A significant decrease in plasma progesterone concentrations was observed in Group 1 mares (12.08 ± 3.91 ng/ml at flushing vs 0.7 ± 0.28 ng/ml at 48h, p<0.001) but not in Group 2 (12.62 ± 4.76 ng/ml at flushing vs 10.89 ± 3.57 ng/ml at 48h, p=0.549). The inter-ovulatory interval was shorter in Group 1 compared to Group 2 mares (18.56 ± 1.94 vs. 20.94 ± 1.84 days, respectively; p=0.006). Only 2 cycles had follicles ≥28mm at the time of embryo flushing and PGF2α was not administered in those cycles. Although the IOI was shortened by a mean of 2.38 days in mares given PGF2α, this was less than the 5-6 days which the dioestrous phase of the cycle had been shortened by. Based on the results obtained in this study, manipulation of the reproductive tract during embryo flushing does not result in endogenous release of PGF2α and/or oxytocin that is sufficient to cause luteolysis of the CL or cause a significant decrease in serum progesterone levels in embryo donor mares.