Multidisciplinary team training in postpartum hemorrhage: impact on the use of blood products.

Objective: Compare the number of puerperal women submitted to blood transfusion before and after the implementation of a care protocol for postpartum hemorrhage (PPH) with multidisciplinary team training. Methods: Cross-sectional study in a university hospital, analyzing births from 2015 to 2019, compared the use of blood products before and after the adoption of a PPH protocol with multidisciplinary training. Results: Between 2015 and 2019, there were 17,731 births, with 299 (1.7%) postpartum women receiving blood products and 278 postpartum women were considered for this analysis, 128 (0.7%) at Time 1 and 150 (0.8%) at Time 2. After the multiprofessional team training (T2), there was a difference in the complete use of the PPH protocol (use of oxytocin, misoprostol and tranexamic acid) (T1 = 5.1% x T2 = 49.5%, p≤0.0001). An individual categorized analysis revealed that, in the T2 period, there was lower use of blood component units per patient compared to T1 (Mann-Whitney, p=0.006). It should be noted that at T1 and T2, 54% and 24% respectively received two units of blood products. It is important to highlight that after the multidisciplinary team training for the PPH protocol, the goal of zero maternal death due to hemorrhage was reached. Conclusion: The adoption of a specific protocol for PPH, combined with the training of a multidisciplinary team, had an impact on the ability to identify women at high risk of hemorrhage, resulting in a decrease in the use of blood components.

(-)-Carvone Inhibits Oxytocin-induced Writhing Via Uterine Relaxation in Rodents.

(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.

High-dose versus low-dose oxytocin for labor augmentation: a meta-analysis of randomized controlled trials

BACKGROUND/OBJECTIVES: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. RESULTS: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). CONCLUSIONS: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.

From molecular variations to behavioral adaptations: Unveiling adaptive epistasis in primate oxytocin system.

OBJECTIVE: Our primary objective was to investigate the variability of oxytocin (OT) and the GAMEN binding motif within the LNPEP oxytocinase in primates. MATERIALS AND METHODS: We sequenced the LNPEP segment encompassing the GAMEN motif in 34 Platyrrhini species, with 21 of them also sequenced for the OT gene. Our dataset was supplemented with primate sequences of LNPEP, OT, and the oxytocin receptor (OTR) sourced from public databases. Evolutionary analysis and coevolution predictions were made followed by the macroevolution analysis of relevant amino acids associated with phenotypic traits, such as mating systems, parental care, and litter size. To account for phylogenetic structure, we utilized two distinct statistical tests. Additionally, we calculated binding energies focusing on the interaction between Callithtrix jacchus VAMEN and Pro8OT. RESULTS: We identified two novel motifs (AAMEN and VAMEN), challenging the current knowledge of motif conservation in placental mammals. Coevolution analysis demonstrated a correlation between GAMEN, AAMEN, and VAMEN and their corresponding OTs and OTRs. Callithrix jacchus exhibited a higher binding energy between VAMEN and Pro8OT than orthologous molecules found in humans (GAMEN and Leu8OT). DISCUSSION: The coevolution of AAMEN and VAMEN with their corresponding OTs and OTRs suggests a functional relationship that could have contributed to specific reproductive and adaptive behaviors, including paternal care, social monogamy, and twin births, prominent traits in Cebidae species, such as marmosets and tamarins. Our findings underscore the coevolution of taxon-specific amino acids among the three studied molecules, shedding light on the oxytocinergic system as an adaptive epistatic repertoire in primates.

Uterotonics, magnesium sulphate and antibiotics during childbirth and peripartum: Important obstetric drugs for the anaesthesiologist.

The main causes of maternal mortality are comorbidities, hypertensive pregnancy syndrome, obstetric haemorrhage, and maternal sepsis. For this reason, uterotonics, magnesium sulphate, and antibiotics are essential tools in the management of obstetric patients during labour and in the peripartum period. These drugs are widely used by anaesthesiologists in all departments, and play a crucial role in treatment and patient safety. For the purpose of this narrative review, we performed a detailed search of medical databases and selected studies describing the use of these drugs in patients during pregnancy, delivery and the pospartum period. Uterotonics, above all oxytocin, play an important role in the prevention and treatment of pospartum haemorrhage, and various studies have shown that in obstetric procedures, such as scheduled and emergency caesarean section, they are effective at lower doses than those hitherto accepted. We also discuss the use of carbetocin as an effective alternative that has a therapeutic advantage in certain clinical circumstances. Magnesium sulphate is the gold standard in the prevention and treatment of eclampsia, and also plays a neuroprotective role in preterm infants. We describe the precautions to be taken during magnesium administration. Finally, we discuss the importance of understanding microbiology and the pharmacology of antibiotics in the management of obstetric infection and endometritis, and draw attention to the latest trends in antibiotic regimens in labour and caesarean section.

Methods of induction and augmentation of labor in a freestanding birth center: a cross-sectional study.

OBJECTIVE: To describe and analyze the use of methods of induction and augmentation of labor in a freestanding birth center (FBC). METHOD: Cross-sectional study carried out at a FBC located in São Paulo (SP), with all women booked from 2011 to 2021 (n = 3,397). RESULTS: The majority of women (61.3%) did not receive any method. The methods were used alone or in combination (traditional Chinese medicine, massage, castor oil, stimulating tea, amniotomy, and oxytocin). Traditional Chinese medicine (acupuncture, acupressure, and moxa) was the most used method (14.7%) and oxytocin was the least frequent (5.1%). The longer the water breaking time, the greater the number of methods used (p < 0.001). Amniotomy was associated with maternal transfers (p < 0.001). CONCLUSION: Induction and augmentation of labor were strictly adopted. The use of natural or non-pharmacological methods prevailed. Robust clinical studies are needed to prove the effectiveness of non-pharmacological methods of stimulation of childbirth, in addition to strategies for their implementation in other childbirth care services, to really prove the effectiveness of non-pharmacological methods in the parturition process, that is, in labor and birth.

Effects of physical training on hypothalamic neuronal activation and expressions of vasopressin and oxytocin in SHR after running until fatigue.

To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.

Oxytocin alleviates periodontitis in adult rats.

OBJECTIVE: The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis. BACKGROUND DATA: Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease. METHODS: We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 µg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1ß, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR. RESULTS: We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1ß (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model. CONCLUSIONS: Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.

Oxytocin neuron activation by acute infusion of Montanoa genus plants in the Wistar rats / Activación de neuronas de oxitocina por la infusión aguda de plantas del género de Montanoa en la rata Wistar

In tradition al Mexican medicine, plants from the Montanoa genus, family Asteraceae ( Montanoa tomentosa , Montanoa grandiflora , and Montanoa frutescens ) have been used to induce labor owing to their uterotonic properties like those produced by oxytocin (OXT). However, w hether infusions of these plants can activate hypothalamic OXT - producing neurons is unknown. To test this possibility, five independent groups of Wistar rats (n=4) were included: intact, vehicle, and three groups that received 50 mg/kg p.o. of M. tomentosa , M. grandiflora , and M. frutescens infusions, respectively. Ninety min after treatment, the brains were obtained and processed using double - labeled immunohistochemistry for Fos protein and oxytocin (Fos/OXT - ir). Rats that received Montanoa infusions had s ignificantly greater number of Fos/OXT - ir cells in the paraventricular (PVN) and supraoptic (SON) nuclei, with respect to intact and vehicle groups. These findings demonstrate that Montanoa infusions activated OXT neurons, an effect that may be related to the reported pharmacological properties.

En la medicina tradicional mexicana, plantas del género Montanoa , familia Asteraceae ( Montanoa tomentosa , Montanoa grandiflora y Montanoa frutescens ), se han utilizado para inducir el parto debido a sus propiedades uterotónicas, aparentemente similares a las producidas por la hormona oxitocina (OXT). Sin embargo, se desconoce si las infusiones de estas plantas pueden activar neuronas hipotalámicas productoras de OXT. Para probar esta posibilidad, se incluyeron cinco grupos independientes (n=4): intacto, vehículo y tres grupos que recibieron 50 mg/kg p.o. de infusiones de M. tomentosa , M. grandiflora , y M. frute scens , respectivamente. Noventa minutos después del tratamiento, los cerebros fueron obtenidos y procesados por doble marcaje de inmunohistoquímica para la proteína Fos y oxitocina (Fos/OXT - ir). Las ratas que recibieron infusiones de Montanoa aumentaron si gnificativamente el número de células Fos/OXT - ir en los núcleos paraventricular (PVN) y supraóptico (SON), respecto a los grupos intacto y vehículo. Estos hallazgos demuestran que las infusiones de Montanoa activan neuronas de OXT, lo que podría estar rela cionado con sus propiedades farmacológicas

Role of serotonin, estrogen, and TNF-α in the paroxetine-impaired steroidogenesis and testicular macrophages polarization.

BACKGROUND: Paroxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, has caused male sexual dysfunction; however, the paroxetine mechanisms of action in testes are still unclear. OBJECTIVES: Paroxetine serotonergic effects in testes were evaluated, focusing on steroidogenesis and the correlation between macrophages population and possible TNF-α-derived oxidative stress. We also verified whether the changes are reversible following treatment interruption. MATERIALS AND METHODS: Adult rats received paroxetine (PG35 and PG65) or tap water (CG) for 35 days. PG65 was maintained without treatment for 30 more days. Intratesticular testosterone (IT), nitrite, and malondialdehyde concentrations were measured. To confirm serotonergic and estrogenic effects, Htr1b and Esr1 expressions were analyzed. The daily sperm production (DSP), frequency of abnormal seminiferous tubules (ST), SC number, ST area, and Leydig cells nuclear area (LCnu) were evaluated. TUNEL+ germ cells, M1 (CD68+ ), and M2 (Perls+ ) macrophages were quantified. 17ß-HSD7, CYP19A1, NDRG2, oxytocin, TNF-α, and iNOS were evaluated by immunoreactions. Oxytocin and NDRG2 protein levels as well as Tnfa mRNA expression were also analyzed. RESULTS: The Htr1b downregulation in testes confirmed the paroxetine serotonergic effect. The testicular sections showed abnormal ST frequency, ST atrophy and reduction of DSP, LCnu, SC number and Perls+ macrophages. TUNEL+ germ cells and LC were associated with strong NDRG2 immunoexpression. Paroxetine reduced IT levels and 17ß-HSD7 immunoexpression in parallel to increased CYP19A1, oxytocin, TNF-α and iNOS. Esr1 and Tnfa overexpression and increased number of CD68+ macrophages were also observed together with high nitrite and malondialdehyde levels. Most parameters were not recovered in PG65. CONCLUSIONS: Paroxetine serotonergic effect impairs LC steroidogenesis, via aromatization, increasing estrogen/testosterone ratio, which in turn upregulate NDRG2, promoting apoptosis, and impairing sperm production. Serotonin-estrogen pathways may be responsible for M2/M1 polarization, Tnfa upregulation, and induction of oxidative stress. The unrecovered testicular changes after treatment discontinuation are due to persistent paroxetine serotonin/estrogen effects.

Vasotocin but not isotocin is involved in the emergence of the dominant-subordinate status in males of the weakly electric fish, Gymnotus omarorum.

The establishment of the dominant-subordinate status implies a clear behavioral asymmetry between contenders that arises immediately after the resolution of the agonistic encounter and persists during the maintenance of stable dominance hierarchies. Changes in the activity of the brain social behavior network (SBN) are postulated to be responsible for the establishment and maintenance of the dominant-subordinate status. The hypothalamic nonapeptides of the vasopressin (AVP) and oxytocin (OT) families are known to modulate the activity of the SBN in a context-dependent manner across vertebrates, including status-dependent modulations. We searched for status-dependent asymmetries in AVP-like (vasotocin, AVT) and OT-like (isotocin, IT) cell number and activation immediately after the establishment of dominance in males of the weakly electric fish, Gymnotus omarorum, which displays the best understood example of non-breeding territorial aggression among teleosts. We used immunolabeling (FOS, AVT, and IT) of preoptic area (POA) neurons after dyadic agonistic encounters. This study is among the first to show in teleosts that AVT, but not IT, is involved in the establishment of the dominant-subordinate status. We also found status-dependent subregion-specific changes of AVT cell number and activation. These results confirm the involvement of AVT in the establishment of dominance and support the speculation that AVT is released from dominants' AVT neurons.

Assessing the effects of oxytocin in changes of core body temperature during LPS-induced endotoxemia: A novel approach using Extended Poincaré Plot Analysis.

Oxytocin has shown cardioprotective effects during inflammation and may modify the core body temperature changes in LPS-induced endotoxemia. Notably, the time series analysis of core body temperature fluctuations may indicate thermoregulation alterations. This study aims to assess the effects of oxytocin on changes in the core body temperature by analyzing the fluctuations of the temperature time series of endotoxemic rats. Twelve hours of continuous core body temperature fluctuations time series were obtained from adult male Dark Agouti rats implanted with a telemetric transmitter under the following treatment: lipopolysaccharide (LPS); oxytocin (O); lipopolysaccharide + oxytocin (LPS + O), and vehicle or control (C). The temperature fluctuations time series were analyzed using the Extended Poincaré Plot Analysis (EPPA), a novel approach for measuring nonlinear features, to compute the autocorrelation by Pearson's correlation coefficient r, the standard deviation perpendicular to the line of identity (SD1), and the standard deviation parallel to the line of identity (SD2). The autocorrelation of the temperature fluctuations assessed by Pearson's coefficient was significantly higher in the LPS group compared to control rats (C). Likewise, the co-administration of oxytocin during endotoxemia (LPS + O) significantly reduced the autocorrelation and increased the short-term variability (SD1) of temperature fluctuations compared to those recorded with a single dose of LPS. Thus, we concluded that oxytocin may introduce thermoregulatory changes under LPS-induced endotoxemia. The EPPA is a simple and powerful approach to assess physiological variability that can provide valuable insights into changes in thermoregulation.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Effects of oxytocin induction on early postpartum hemorrhage, perineal integrity, and breastfeeding: a case-control study.

OBJECTIVE: The aim of this study was to evaluate the postpartum hemorrhage, perineal integrity, and breastfeeding results of mothers who underwent oxytocin induction in the first stage of labor in the early postpartum period. METHODS: This single-center observational case-control study was conducted in the obstetric unit of a public hospital in Istanbul. The study sampling included 44 pregnant women who received oxytocin induction (case group) and 44 pregnant women who did not receive oxytocin (control group). The Personal Information Form, LATCH Breastfeeding Assessment Tool, Breastfeeding Self-Efficacy Scale, Redness, Edema, Ecchymosis, Discharge, and Approximation Scale, and Postpartum Hemorrhage Collection Bag were used in data collection, and pad follow-up was carried out. RESULTS: The amount of hemorrhage in the first 24 h of the postpartum period and the mean Redness, Edema, Ecchymosis, Discharge, and Approximation Scale score were significantly higher in the case group. While 47.7% of the oxytocin-induced women had 1st or 2nd, and 11.4% had 3rd or 4th degrees of lacerations, 20.5% of the control group had 1st or 2nd, and 2.3% had 3rd or 4th degrees of lacerations. There was no significant difference between the mean scores of the Breastfeeding Self-Efficacy Scale and LATCH Breastfeeding Assessment Tool in both groups. CONCLUSION: According to the study findings, it was determined that oxytocin induction administered in the first stage of labor increased hemorrhage and perineal trauma in the early postpartum period but did not affect the results of breastfeeding. CLINICAL TRIAL REGISTRATION NUMBER: NCT04441125.

Increased proliferation and neuronal fate in prairie vole brain progenitor cells cultured in vitro: effects by social exposure and sexual dimorphism.

BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.

In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.

Transcervical artificial insemination in the brown brocket deer (Subulo gouazoubira): a promising method for assisted reproduction in deer.

The present study aimed to test the efficiency of transcervical artificial insemination techniques with cervical immobilization (TCAI-CI) or cervical traction (TCAI-CT), associated or not with the use of oxytocin (OT) as a protocol for cervical dilation, in the brown brocket deer (Subulo gouazoubira). The study was carried out in a crossover design using four adult females in two replicates with an interval of 60 days. Estrus was synchronized with oral melengestrol acetate (MGA) associated with estradiol benzoate and sodium cloprostenol. TCAI techniques were performed from 18 to 24 h after estrus onset. All females received either an i.v. application of 50 IU of OT (G-OT, n = 4) or 1 mL of saline solution (G-Control, n = 4) 20 min before the TCAI procedure. The TCAIs were performed using frozen-thawed semen motility 40%, vigor 3, acrosome integrity 87%, membrane integrity of 95% and 13% of total post-thaw defects from the same batch. Behavioral estrus was observed in 100% of the females, in both replicates. It was achieved a 50% (4/8) success of cervical transposition with semen deposition in the uterine. Regarding inseminations, most of them (87.5%) were performed using the TCAI-CT technique, and the overall conception rate was 50%. Cervical transposition times (< 1 min) and TCAI procedures (~ 17 min) were considered satisfactory. Thus, the performance of the TCAI-CI and TCAI-CT techniques was successful, regardless of using OT as a cervical dilation protocol. This procedure is proposed as a method of choice for artificial insemination with greater applicability in different conservation centers, compared to more advanced reproductive biotechniques, and with a favorable impact on the conservation of deer species.

Non-canonical Ca2+- Akt signaling pathway mediates the antiproteolytic effects induced by oxytocin receptor stimulation in skeletal muscle.

Although it has been previously demonstrated that oxytocin (OXT) receptor stimulation can control skeletal muscle mass in vivo, the intracellular mechanisms that mediate this effect are still poorly understood. Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. The results indicated that both OXT and WAY-267,464 suppressed muscle proteolysis, and this effect was blocked by the addition of ATB. Furthermore, the WAY-induced anti-catabolic action on protein metabolism did not involve the coupling between OXTR and Gαi since it was insensitive to pertussis toxin (PTX). The decrease in overall proteolysis induced by WAY was probably due to the inhibition of the autophagic/lysosomal system, as estimated by the decrease in LC3 (an autophagic/lysosomal marker), and was accompanied by an increase in the content of Ca2+-dependent protein kinase (PKC)-phosphorylated substrates, pSer473-Akt, and pSer256-FoxO1. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca2+ release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca2+-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis.

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.

Cocaine use disorder effects on blood oxytocin levels and OXTR DNA methylation.

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.

What do healthcare providers think of the quality of uterotonics? A mixed-methods systematic review.

OBJECTIVES: To synthesise evidence on the perceptions of healthcare providers (HCPs) about the quality of oxytocin and misoprostol available in their settings, and their actions as a result of these perceptions. DESIGN: Mixed-methods systematic review. ELIGIBILITY CRITERIA: We included quantitative and qualitative studies reporting HCPs' perceptions about oxytocin or misoprostol quality. DATA SOURCES: We searched CINAHL, Cochrane Library, Ebscohost, Embase, PubMed, Global Index Medicus, Portal regional BVS, PsycNET, Scopus and Web of Science from inception to 31 March 2022 and grey literature. RISK OF BIAS: We used the Center for Evidence-Based Management critical appraisal tool for surveys. For qualitative studies, we used the Critical Appraisal Skills Programme tool. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers performed study selection, data extraction and quality assessment. We conducted separate quantitative and qualitative syntheses and integrated the evidence into a narrative synthesis (convergent segregated review design). RESULTS: We included five (three quantitative and two qualitative) studies, of moderate or high quality, conducted in low-income and middle-income countries (LMICs). In the three quantitative studies (N=7065 participants), 8.2-21.3% of HCPs had experienced problems due to known/suspected low-quality oxytocin and 3.3% due to low-quality misoprostol. In the two qualitative studies, perception of oxytocin quality varied. In quantitative studies, when confronted with suspected/known low-quality oxytocin, 29-78% of HCPs would inform a supervisor, 62% would document this in writing, 45-54% would change to another drug and 5-37% would double the dose of oxytocin. Qualitative evidence suggests that many HCPs do not formally report suspected low-quality oxytocin or misoprostol, and use higher doses or additional uterotonics. CONCLUSIONS: A proportion of HCPs from LMICs perceive oxytocin to be of low quality. There is very limited evidence on their perceptions about misoprostol. Many HCPs do not report suspected low-quality uterotonics but change to another medicine or double the dose of oxytocin. PROSPERO REGISTRATION NUMBER: CRD42022323812.