Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.

Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders. VIDEO ABSTRACT.

Primiparas' prenatal depressive symptoms, anxiety, and salivary oxytocin level predict early postnatal maternal-infant bonding: a Japanese longitudinal study.

PURPOSE: It was reported that maternal-infant bonding failure predicts abusive parenting. Maternal-infant bonding is important to prevent child abuse. This study aimed to investigate the association between prenatal depressive symptoms, anxiety, cortisol, and oxytocin levels, and postnatal maternal-infant bonding. METHODS: The participants completed a self-report prenatal questionnaire that included the Edinburgh Postnatal Depression Scale (EPDS) and State-Trait Anxiety Inventory (STAI) in the second trimester. Blood and saliva were collected in the second trimester. Cortisol levels were measured in plasma, while oxytocin levels were measured in saliva. Postnatal questionnaires, including the Mother-to-Infant Bonding Scale (MIBS), were administered at 2-5 days, 1 month, and 3 months postpartum. Multiple linear regression and generalized estimating equation (GEE) were conducted for analysis. RESULTS: Sixty-six primiparas participated in the study. Prenatal depressive symptoms (EPDS ≥ 9) and anxiety (STAI-S ≥ 42) were observed in 21.2% and 28.8% of the participants, respectively. The median cortisol and oxytocin levels were 21.0 µg/dL and 30.4 pg/mL, respectively. Multivariate linear regression showed that postnatal social support, prenatal depressive symptoms, anxiety, and salivary oxytocin levels predicted MIBS scores at 2-5 days postpartum. At 1 month postpartum, household income, history of miscarriage, postnatal social support, and prenatal anxiety predicted MIBS scores. At 3 months postpartum, only postnatal social support predicted MIBS scores. The results of GEE showed that prenatal anxiety, oxytocin levels, postpartum period, household income, and postpartum social support were associated with MIBS scores. CONCLUSION: Prenatal depressive symptoms, anxiety, and lower salivary oxytocin levels were predicted to worsen maternal-infant bonding at 2-5 days postpartum. Prenatal anxiety was predicted to cause the same 1 month postpartum. Measuring prenatal depressive symptoms, anxiety, and salivary oxytocin levels may render the assessment of the risk of maternal-infant bonding failure during the early postpartum period and intervene during pregnancy possible.

Estimation of udder emptying based on milk constituents of strip samples after milking.

Milk ejection disorders were induced by oxytocin receptor blockade. We tested the hypothesis that the degree of udder emptying at incomplete milk ejection can be estimated based on the concentration of various milk constituents in different milk fraction samples. To induce different levels of spontaneous udder emptying (SUE) 10 Holstein dairy cows were milked either with or without i.v. injection of the oxytocin receptor blocking agent atosiban (ATO). In ATOearly, 12 µg/kg BW ATO was injected immediately before and in ATOlate directly after a 1-min manual udder preparation. The normal milking routine served as the control treatment. In all 3 treatments the udder was completely emptied by the i.v. injection of 10 IU oxytocin (OT) at the end of spontaneous milk flow. During all experimental milkings 4 milk samples were taken in all treatments: at the start of udder preparation (foremilk; FM), immediately after cessation of spontaneous milk flow and cluster detachment by hand stripping (strip milk; SM), from spontaneous removed milk in bucket 1 (milk before OT; MBOT) and from the milk obtained after OT injection in bucket 2 (milk after OT; MAOT). Fat, protein, lactose, and electrolytes (Na, Cl, and K) were measured in each milk sample. In addition, electrical conductivity (EC) was determined in parallel to continuous milk flow recording. The treatments induced individual degrees of SUE; therefore, the final evaluations of data were based on SUE classes instead of treatments. The most pronounced differences of milk constituents at different degrees of SUE were found for the milk fat content. The fat content of SM and MBOT remained almost unchanged up to 60% SUE, but was considerably higher if >80% of the milk was spontaneously removed. The concentrations of Na and Cl were highest and of K lowest if less than 20% of milk was received in the different samples. The EC was higher in SM and MBOT if <20% of milk was received. In conclusion, the blockade of the OT effect influences primarily the fat content, which confirmed an OT-induced fat secretion during milking. Similar effects are likely found in situations of disturbed milk ejections, caused by a lack of or reduced release of OT in response to different degrees of tactile udder stimulation. Our results show that the measurement of fat content and the EC in SM samples collected after cluster detachment can be used to estimate the completeness of udder emptying.

Highly Specific Detection of Oxytocin in Saliva.

Oxytocin is a peptide neurophysin hormone made up of nine amino acids and is used in induction of one in four births worldwide (more than 13 percent in the United States). Herein, we have developed an antibody alternative aptamer-based electrochemical assay for real-time and point-of-care detection of oxytocin in non-invasive saliva samples. This assay approach is rapid, highly sensitive, specific, and cost-effective. Our aptamer-based electrochemical assay can detect as little as 1 pg/mL of oxytocin in less than 2 min in commercially available pooled saliva samples. Additionally, we did not observe any false positive or false negative signals. This electrochemical assay has the potential to be utilized as a point-of-care monitor for rapid and real-time oxytocin detection in various biological samples such as saliva, blood, and hair extracts.

Endogenous oxytocin levels in extracted saliva elevates during breastfeeding correlated with lower postpartum anxiety in primiparous mothers.

BACKGROUND: Breastfeeding in the early postpartum period is expected to have mental benefits for mothers; however, the underlying psychobiological mechanisms remain unclear. Previously, we hypothesized that the release of oxytocin in response to the suckling stimuli during breastfeeding would mediate a calming effect on primiparous mothers, and we examined salivary oxytocin measurements in primiparous mothers at postpartum day 4 using saliva samples without extraction, which was erroneous. Thus, further confirmation of this hypothesis with a precise methodology was needed. METHODS: We collected saliva samples at three time points (baseline, feeding, and post-feeding) to measure oxytocin in 24 primiparous mothers on postpartum day 2 (PD2) and 4 (PD4) across the breastfeeding cycle. Salivary oxytocin levels using both extracted and unextracted methods were measured and compared to determine the qualitative differences. State and trait anxiety and clinical demographics were evaluated to determine their association with oxytocin changes. RESULTS: Breastfeeding elevated salivary oxytocin levels; however, it was not detected to a significant increase in the extraction method at PD4. We found a weak but significant positive correlation between changes in extracted and unextracted oxytocin levels during breastfeeding (feeding minus baseline); there were no other significant positive correlations. Therefore, we used the extracted measurement index for subsequent analysis. We showed that the greater the increase in oxytocin during breastfeeding, the lower the state anxiety, but not trait anxiety. Mothers who exclusively breastfed at the 1-month follow-up tended to be associated with slightly higher oxytocin change at PD2 than those who did not. CONCLUSIONS: Breastfeeding in early postpartum days could be accompanied by the frequent release of oxytocin and lower state anxiety, potentially contributing to exclusive breastfeeding.

Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice.

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.

Oxytocin receptor gene polymorphism and low serum oxytocin level are associated with hyperphagia and obesity in adolescents.

BACKGROUND/OBJECTIVES: In recent years, oxytocin (OXT) and polymorphisms in the oxytocin receptor (OXTR) gene have been reported to play roles in obesity pathogenesis. However, there was no study evaluating OXTR gene variants in childhood obesity. The aim of the study was to investigate the relation of OXTR gene polymorphisms and serum OXT levels with metabolic and anthropometric parameters in obese and healthy adolescents. SUBJECTS/METHODS: The study was a multi-centered case-control study, which was conducted on obese and healthy adolescents aged between 12 and 17 years. Serum OXT and leptin levels were measured, and OXTR gene variants were studied by qPCR (rs53576) and RFLP (rs2254298) methods. RESULTS: A total of 250 obese and 250 healthy adolescents were included in this study. In the obese group, serum OXT level was lower and leptin level was higher than the control group. In the obese group, frequencies of homozygous mutant (G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were higher than the control group. Homozygous mutant(G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were found to increase the risk of obesity compared to the wild type (A/A) genotype [OR = 6.05 and OR = 3.06; p < 0.001, respectively]. In patients with homozygous mutant (G/G) and heterozygous (A/G) genotype for rs53576 polymorphism, serum OXT levels were lower than the wild type (A/A) genotype. In the obese group, hyperphagia score was higher than the control group and correlated negatively with serum OXT level. CONCLUSIONS: This study revealed that low serum OXT level, which is associated with hyperphagia may be an underlying cause for obesity in adolescents. For rs53576 polymorphism of the OXTR gene, obesity risk is higher in patients with homozygous mutant(G/G) and heterozygous(A/G)genotypes.

Structurally related peptide impurity identification and accurate quantification for synthetic oxytocin by liquid chromatography-high-resolution mass spectrometry.

Oxytocin (OXT) is an important peptide that is mainly used as a therapeutic drug to induce labor or strengthen uterine contractions, or to control bleeding after childbirth. OXT has also been reported as a biomarker linked to emotion, and as a potential biomarker for cancer diagnosis. The accurate purity characterization of OXT calibrators is critical for quality control of pharmaceuticals and the development of reference measurement systems for this analyte in laboratory medicine. OXT possesses the particular analytical measurement challenge of a disulfide bond. Accurate value assignment of the purity of oxytocin calibrators can be carried out by applying the mass balance approach or alternative approaches such as amino acid analysis, quantitative nuclear magnetic resonance spectrometry, and nitrogen determination. In order to avoid biases, all these approaches require a correction for structurally related peptide impurities. Structurally related peptide impurities present in a synthetic OXT material have been identified and quantified by a newly developed and in-house-validated liquid chromatography-high-resolution mass spectrometry (LC-hrMS) method. This method was adopted for the measurement of the study material used for an international comparison evaluating the competencies of laboratories to perform peptide characterization. Eighteen structurally related impurities were identified, confirmed, and accurately quantified in the OXT study material by using LC-hrMS. The study material contained a total mass fraction of 31.1 mg/g structurally related OXT impurities with an associated expanded uncertainty of 1.7 mg/g.

Changes in the cortisol and oxytocin levels of first-time pregnant women during interaction with an infant: a randomized controlled trial.

BACKGROUND: During pregnancy, physiological, psychological, and social changes affect pregnant women's childcare anxiety and childrearing behavior. However, there are scarce reports on hormonal evaluation related to such anxiety and behavior. Herein, we evaluated changes in salivary cortisol (primary outcome) and oxytocin (secondary outcome) levels of first-time pregnant women when interacting with an infant and discussed the relation of these changes to the women's stress level. METHODS: This was a two-arm randomized controlled trial. Participants were randomly assigned using a web-based randomization system. The experimental group involved interaction with an infant for 30 min. The control group involved watching a DVD movie of an infant for 30 min. Saliva samples were collected at preintervention and postintervention. Saliva samples were assayed, and all data were compared between and within the groups using independent t-test and paired t-test with a two-sided 5% significance level. This study was approved by the Research Ethics Committee of St. Luke's International University. RESULTS: A total of 102 women were randomly assigned to the experimental (n = 51) and control (n = 51) groups. Finally, 38 women in the experimental group and 42 women in the control group were analyzed. The salivary cortisol level significantly decreased after the interventions in both groups (t = 4.57, p = 0.00; t = 5.01, p = 0.00). However, there were no significant differences in the salivary cortisol (t = 0.349, p = 0.73) and oxytocin (t = - 1.945, p = 0.58) levels between the two groups. CONCLUSIONS: The salivary cortisol level of first-time pregnant women significantly decreased in the experimental and control groups postintervention, although no significant difference was found between the two groups. Such decrease indicates stress reduction and release among these women. The absence of a significant increase in salivary oxytocin level in both groups may be related to the limitations of an insufficient number of samples that could be analyzed owing to the small saliva volume in some samples and the lack of adequate tactile stimulation of the intervention protocol. These results and procedural limitations provide useful insights into approaching subsequent studies aiming at continuously optimizing detection procedures. TRIAL REGISTRATION: UMIN000028471 (Clinical Trials Registry of University Hospital Information Network. July 31, 2017- Retrospectively registered.

Demographic, sampling- and assay-related confounders of endogenous oxytocin concentrations: A systematic review and meta-analysis.

Studies on endogenous oxytocin concentrations are often criticized for the debatable comparability between specimens and the variation in reported values. We performed meta-regressions on k = 229 studies (n = 12 741 participants), testing whether specimen, extraction, sex, age, time of day, or fasting instructions influenced oxytocin measurements. Predicted oxytocin concentrations differed depending on specimen and extraction: Measurements were extremely high in unextracted blood, compared to extracted blood and other specimens. Measurements were higher in samples with more female participants and higher age. Instructions not to smoke before sampling were correlated with higher oxytocin in unextracted samples. There was no impact of instructions to refrain from eating, drinking, consume caffeine, alcohol or exercising. Oxytocin concentrations increased from morning to afternoon. Our results showed that oxytocin is differentially reflected in blood, saliva, urine and cerebrospinal fluid. Extraction impacts oxytocin measurements, particularly in blood. Considering relevant confounders might increase comparability between studies.

Experimental empathy induction promotes oxytocin increases and testosterone decreases.

Oxytocin and testosterone coordinate adaptive social behaviors with stimuli in the environment. Administration of oxytocin and testosterone is associated with increased and reduced indicators of empathy, respectively, but how levels of these hormones are jointly affected by naturalistic empathy-inducing stimuli remains unclear. In this study, salivary oxytocin and testosterone levels were measured in 173 healthy adults before and after watching a video involving a gravely ill child. Participants also completed questionnaires to assess psychological variables predicted to affect oxytocin reactivity (Autism-Spectrum Quotient, Interpersonal Reactivity Index, Empathy and Systemizing Quotients). On average, there was a 14% increase in oxytocin (p = 0.003) and 4% decrease in testosterone (p = 0.001) pre- to post-video. Opposite directional changes in hormone levels occurred together, as supported by a chi-square test (p < 0.001) and a circular statistics test (p < 0.05). Considered separately, psychological traits did not predict hormone levels or changes to any appreciable degree. However, oxytocin and testosterone changes were linked with empathy relative to systemizing such that: (1) 'Empathy Bias' was associated with a large oxytocin increase but little change in testosterone, while (2) 'Systemizing Bias' and 'Balance' between empathy and systemizing were associated with a decrease in testosterone but little change in oxytocin. These findings suggest that participants were divisible into 'high oxytocin responders' (relatively empathetic) and 'high testosterone responders' (balanced or systemizing-biased). These findings support a model of joint, opposite changes in oxytocin and testosterone under experimental empathy induction, with high, somewhat predictable, diversity in individual responses.

Quality, availability and storage conditions of oxytocin and misoprostol in Malawi.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs. METHODS: In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017. RESULTS: All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter. CONCLUSION: Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.

Oxytocin Levels Inversely Correlate With Skin Age Score and Solar Damage.

BACKGROUND: Studies have shown oxytocin (OT) and its carrier protein neurophysin 1 are found in the epidermis. The oxytocin receptor, which is found on human fibroblasts has been shown, when activated by oxytocin, to inhibit senescence-associated secretory phenotype (SASP). SASP activation induces the release of proinflammatory cytokines which contribute to skin aging. Therefore, its inhibition by oxytocin would constitute a protective mechanism. This pilot study was designed to explore clinical evidence of oxytocin levels correlating to the skin’s appearance in subjects. METHODS: Oxytocin levels, facial photographs, and lifetime sun exposure questionnaires from six female subjects aged 48–61 years old were analyzed. A skin age score (SAS) was determined for each subject and was compared to the expected average SAS for each subject based on their age to determine a percentage in change, if any. A reduction in SAS would indicate more youthful appearing skin than the average person of that age. RESULTS: All subjects had at least some reduction in SAS score as compared to their expected score. An almost linear relationship of SAS reduction as related to OT levels was found, showing a correlation of more youthful appearing skin with higher OT levels. CONCLUSIONS: This study links previously published evidence of oxytocin’s protective role against inflammatory cytokine release in the skin with clinical evidence of OT levels correlating with SAS scores. Furthermore, it shows OT is likely inducing a protective function in the epidermis in the case of sun exposure and possibly with intrinsic aging. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5063.

Monolithic and core-shell particles stationary phase morphologies in protein analysis; peptide mapping of erythropoietin hormone and determination of carbetocin.

Chromatographic application of two recent HPLC stationary phases for protein analysis was demonstrated. These two stationary phases are namely monolithic rods and core-shell particles. Monolithic rods have higher permeability and larger porous structure allowing faster elution, while smaller core-shell particles have narrower particle size distribution and better packing allowing larger number of resolved peptides. Peptide mapping of erythropoietin hormone, which is used in the treatment of symptomatic anaemia associated with chronic renal failure in adult and pediatric patients, was carried out on monolithic column and core-shell particles. Comparison between the effectiveness of separation on both columns was established and the new morphologies proved their capability of replacing the totally porous particles with higher resolution power at shorter analysis time. Carbetocin is an oxytocin analogue with a longer duration of action that stimulates uterine contraction and milk ejection in mammals. Monolithic column was also applied for quantitative HPLC analysis of carbetocin using ethanol as cheap and greener alternative organic modifier without compromise to a full impurity profiling. The proposed method was validated concerning with accuracy, precision, robustness, sensitivity, limits of detection and quantitation and proved to be green and stability indicating.

Detection of oxytocin, atrial natriuretic peptide, and brain natriuretic peptide using novel imprinted polymers produced with amphiphilic monomers.

The cystine-bridged cyclic peptide hormones (CBCPHs) represent signature structural feature as well as unique biological activity. In this study, three CBCPHs have been identified and characterized, namely, oxytocin, atrial natriuretic peptides (ANPs), and brain natriuretic peptides (BNPs). Because research has shown that ANPs and BNPs are powerful diagnostic biomarkers for heart disease, a highly laudable endeavor would be to develop a novel sensor for detecting ANP or BNP levels. Therefore, an amphiphilic monomer Acr-His-NHNH-Fmoc was synthesized to form molecularly imprinted polymers (MIPs) for targeted CBCPH detection. First, oxytocin, a cardiovascular hormone and a CBCPH, was used as a template to fabricate MIPs on quartz crystal microbalance (QCM) chips. On the other hand, fabricated selected ANP segment or BNP segment as an epitope is able to construct epitope-mediated MIPs (EMIPs) for ANP or BNP. The developed oxytocin or ANP sensor reached a detection limitation of 0.1nM with the dissociation constants being 30pM for oxytocin and 20pM for ANP. Moreover, BNP sensor achieved a detection limitation of 2.89pM with an even lower Kd value as 2pM. Compared with the performance of EMIPs, the imprinted films showed high affinity and selectivity in special binding to CBCPHs. The developed MIPs-QCM biosensors thus provide an improved sensing platform using an amphiphilic monomer and may be useful for applications toward cyclotides, cystine knot motifs, or insulin-like peptides.

Combined Proinflammatory Biomarkers Have Better Predictive Value for Term Labor than Single Markers.

BACKGROUND The timing of parturition is an important determinant of labor and delivery care. Early parturition is associated with increased neonatal morbidity and mortality. Most existing studies analyzed a single factor for the initiation of parturition, and the role of multiple factors in initiating parturition has not been comprehensively analyzed. MATERIAL AND METHODS We measured the levels of proinflammatory mediators, hypoxia factor, matrix metalloproteinases, hormones, and oxytocin, as well as fetal umbilical blood flow, before and after labor, and their associations with parturition. We also built a statistical model to predict the timing of parturition based on the measurement data. RESULTS IL-1ß, IL-6, TNF-alpha, MMP-9, and HIF-1alpha concentrations significantly increased from full term to labor. The PRL level significantly decreased from full term to parturition. There was no significant change in MCP-1, E3, and OT concentrations from full term to parturition. IL-1ß, IL-6, TNF-alpha, and MMP-9 concentrations were negatively correlated with the initiation of parturition. There was a small but nonsignificant increase in umbilical venous blood flow before parturition. Multiple factors showed a close correlation with the initiation of parturition, and area under the curve analysis showed that a multiple factor model was superior to single factors in the establishment of a model to predict initiation of parturition; however, these results need further confirmation. CONCLUSIONS Combined proinflammatory biomarkers have better predictive value for term labor than single biomarkers.

Development and Validation of a Simple LC-MS Method for the Quantification of Oxytocin in Dog Saliva.

Oxytocin (OT) is a mammalian neuropeptide with various functions in regulating birth, lactation, parenting, and social recognition. The study of OT became of increasing interest for the petcare industry due to its role in animal behavior and socialization. In the present study, a simple, sensitive, and accurate liquid chromatography-mass spectrometry (LC-MS) method for quantifying OT in dog saliva was developed and validated. OT and its deuterated internal standard (OT-d5) were detected with multiple reaction monitoring (MRM) in a positive ion mode using an AB Sciex 6500+ QTRAP mass spectrometer. Chromatographic separation was achieved by using an ACE Excel C18 column and a gradient elution at a flow rate of 0.5 mL/min over a 5 min run. The mobile phases consisted of 0.1% (v/v) acetic acid in water and 0.1% (v/v) acetic acid in acetonitrile. After development and optimization, the performance of the method was validated to prove its reliability. Calibration curves were linear over the range of 50-20,000 pg/mL and recovery of OT was above 87.8%. The validated method was successfully applied to evaluate OT concentrations in multiple batches of dog saliva samples.

Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements.

Oxytocin and parenting behavior among impoverished mothers with low vs. high early life stress.

Recent work suggests that key aspects of sensitive parenting (e.g., warmth, emotional attunement) may be shaped in part by biology, specifically the neuropeptide oxytocin. However, some studies have found that oxytocin may not act in expected ways in higher-risk populations (e.g., those with postnatal depression or borderline personality disorder). This study examined the relation between oxytocin and parenting among mothers with varying levels of early life stress. Forty low-income mothers and their 34- to 48-month-old child participated in this study. Mother-child dyads were observed in an interaction task in their home, and videos of these interactions were later coded for parenting behaviors. Mothers' oxytocin production before and after the interaction task was assessed through saliva. Mothers' early stress was assessed via the Adverse Childhood Experiences Scale (ACES; Felitti et al. Am J Prev Med 14:245-258, 1998). For mothers with low ACEs, higher oxytocin secretion was associated with more positive parenting. For mothers with high ACEs, higher oxytocin secretion was associated with lower levels of positive parenting. Oxytocin may be operating differently for mothers who experienced harsh early social environments, supporting more defensive behaviors and harsh parenting than anxiolytic and prosocial behaviors.