A systematic review focused on lubricant use and sperm quality: Improving human reproductive success by informing lubricants toxicity.

Lubricants play a pivotal role in human reproductive health, particularly concerning their impact on sperm parameters. In this systematic review, we assess the implications of both synthetic and natural or organic lubricants on sperm health and fertility, based on a compilation of 20 distinct studies. Synthetic lubricants, including K-Y Jelly, Replens, and Astroglide, predominantly containing ingredients like methylparaben and glycerin, have been linked to detrimental effects on sperm motility and chromatin integrity. Chemical characteristics, notably osmolality and pH, are central to understanding these effects. Despite the World Health Organization's osmolality recommendation of 380 mOsm/kg, many commercial products surpass this. Natural solutions offer varied results, while olive oil exhibits unfavorable effects on sperm health, egg white proves non-toxic, potentially benefitting sperm health. Conversely, Pre-Seed, widely endorsed in the research community, generally demonstrates minimal adverse impact on sperm. The review highlights the significance of lubricant selection in evidence-based reproductive strategies.

Técnicas de substituição de DNA mitocondrial para reduzir a transmissão da Síndrome de Leigh / Mitochondrial DNA replacement techniques to reduce Leigh syndrome transmission

A Síndrome de Leigh (SL) é uma doença neuro-metabólica congênita, que faz parte do grupo das encefalopatias fatais, com progressão e morte dentro de 2 anos, em média. A SL é causada por mutações no DNA que causam alterações na geração de ATP celular pelas mitocôndrias. As mitocôndrias contêm seu próprio DNA (mtDNA) e, ao contrário do DNA nuclear, o mtDNA é herdado somente da mãe. Mulheres portadores de mutações causadoras da SL podem vivenciar experiências muito tristes ao tentarem realizar o sonho da maternidade. As técnicas de substituição de mtDNA mutado com mtDNA saudável de doadora, oferecem a essas mulheres a possibilidade de terem uma criança geneticamente relacionada sem a SL. O desenvolvimento e a aplicação clínica de terapias de substituição de mtDNA já são uma realidade, tendo o primeiro bebê gerado a partir da técnica nascido em 2016. Mas será que essas técnicas são seguras? Neste trabalho, revisamos a SL e algumas técnicas de substituição de mtDNA já aplicadas em humanos, que envolvem a transferência de pronúcleos de zigotos ou de fuso acromático de oócitos. Concluímos que, apesar dos resultados promissores, ainda é cedo para assegurar a aplicabilidade clínica de técnicas de substituição de mtDNA em seres humanos. (AU)

Leigh syndrome (SL) is a congenital neurometabolic disease included in the group of fatal encephalopathies, with progression and death within 2 years on average. SL is caused by mutations in the DNA that cause changes in the generation of cellular ATP by mitochondria. Mitochondria contain their own DNA (mtDNA) and, unlike nuclear DNA, mtDNA is inherited only from the mother. Women with SL mutations may experience mournful situations when attempting to fulfill the dream of motherhood. Techniques for replacing mutant mtDNA with healthy donor mtDNA provide these women with the possibility of having a genetically related child without SL. The development and clinical application of mtDNA replacement therapies is a reality, and the first baby generated using the technique was born in 2016. However, are these techniques safe? In this article, we review SL and some mtDNA replacement techniques that have been used in humans, which involve zygote pronuclear transfer or oocyte spindle transfer. We conclude that, despite the promising results, it is too early to ensure that mtDNA replacement techniques are clinically applicable to humans. (AU)

Hippocampal gene expression patterns in oxytocin male knockout mice are related to impaired social interaction.

Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC). AVP gene (Avp) expression was analyzed in the HPT. Gene expression results were discussed regarding to social interaction and sexual behavior findings. Additionally, we analyzed the influence of OT absence on the Avp mRNA expression levels in the HPT. RNA extraction and cDNAs synthesis followed by quantitative polymerase chain reaction were performed for gene expression determination. Results were calculated with the 2-ΔΔCt method. Our main finding was that HPC is more susceptible to gene expression changes due to the lack of OT. OTKOs exhibited decreased expression of Drd2 and Avpr1b, but increased expression of Oxtr in the HPC. In the PFC, Esr2 was increased. In the HPT, there was a reduced Avp expression in the OTKO group. No differences were detected in the OB and HPT. Despite these changes in gene expression, sexual behavior was not affected. However, OTKO showed higher social investigation and lower aggressive performance than wild-type mice. Our data highlight the importance of OT for proper gene expression of neurotransmitter receptors related to the regulation of social interaction in male mice.

Alterações na epigenética do sistema ocitocinérgico em resposta ao cuidado materno negligente / Epigenetics changes into the oxytocinergic system in response to negligent maternal care

O cuidado materno negligente, a falta de afeto e a dificuldade de interagir socialmente estão relacionadas com o desequilíbrio neurofisiológico da ocitocina, neurormônio com papel importante de modulação dos comportamentos sociais. Em seres humanos existem ligações conhecidas entre o estresse pré-natal e perinatal e transtornos psiquiátricos e de desenvolvimento. O objetivo deste estudo foi revisar o conceito de epigenética com foco no efeito a longo prazo do cuidado materno negligente e sua relação com alterações do sistema ocitocinérgico baseado em estudos com animais e humanos. Uma revisão narrativa da literatura foi realizada entre junho de 2017 e janeiro de 2019 através da busca de estudos na base PUBMED, com foco nos resultados qualitativos das relações epigenéticas com a negligência infantil, doenças psiquiátricas e sistema ocitocinérgico. Os estudos referidos demonstram que o cuidado materno negligente é um fator de risco para o desenvolvimento de transtornos mentais, principalmente os que incluem sintomas de desordem social. A ocitocina, por agir como uma potente mediadora das interações sociais, confiança e controle da ansiedade, parece ter papel fundamental neste contexto. A notória transgeracionalidade dos transtornos encontrados em proles de mães negligentes parece estar envolvida com mecanismos epigenéticos que inativam genes específicos do sistema ocitocinérgico no sistema nervoso central. (AU)

Negligent maternal care, lack of affection and difficulty in social interaction are related to a neurophysiological imbalance in oxytocin levels, an important modulator of social behaviors. In humans there are known links between prenatal and perinatal stress and psychiatric and developmental disorders. This study aimed to review the concept of epigenetics with a focus on the long-term effect of negligent maternal care and its relationship to changes in the oxytocinergic system, based on animal and human studies. A narrative review of the literature was conducted using studies from June 2017 to January 2019 available in the PUBMED database, focusing on qualitative results of epigenetic relationships with child neglect, psychiatric diseases and oxytocinergic system. These studies demonstrate that negligent maternal care is a risk factor for the development of mental disorders, especially those that include symptoms of social disorder. Oxytocin, as a neurohormone that acts as a potent mediator of social interactions, confidence and anxiety control, seems to play a fundamental role in this context. The notorious transgenerationality of the disorders found in the offspring of negligent mothers seems to be due to epigenetic mechanisms that inactivate specific genes of the oxytocinergic system in the central nervous system.

The Impact of Oxytocin Gene Knockout on Sexual Behavior and Gene Expression Related to Neuroendocrine Systems in the Brain of Female Mice.

Social relations are built and maintained from the interaction among individuals. The oxytocin (OT), vasopressin (VP), estrogen, dopamine, and their receptors are involved in the modulation of sexual behavior in females. This study aimed to analyze the impact of OT gene knockout (OTKO) on sexual behavior and the gene expression of oxytocin (OTR), estrogen alpha (ERα), estrogen beta (ERß), vasopressin (V1aR), and dopamine (D2R) receptors in the olfactory bulb (OB), prefrontal cortex (PFC), hippocampus (HPC), and hypothalamus (HPT), as well as in the synthesis of VP in the HPT of female mice. Wild-type (WT) littermates were used for comparisons. The CDNAs were synthesized by polymerase chain reaction and the gene expression was calculated with the 2-ΔΔCt formula. Our results showed that the absence of OT caused an increase in the frequency and duration of non-receptive postures and a decrease in receptive postures in the OTKO. OTKO females showed a significant decrease in the gene expression of OTR in the HPC, V1aR in the HPT, and ERα and ERß in the PFC. There was no significant difference in the gene expression of D2R of OTKO. However, OTKO showed an increased gene expression of V1aR in the HPC. There is no significant difference in VP mRNA synthesis in the HPT between OTKO and WT. Our findings demonstrate that the absence of OT leads to significant changes in the expression of the studied genes (OTR, ERα, ERß, V1aR), and these changes may contribute to the decreased sexual behavior observed in OTKO females.

Examining the Role of Vasopressin in the Modulation of Parental and Sexual Behaviors.

Vasopressin (VP) and VP-like neuropeptides are evolutionarily stable peptides found in all vertebrate species. In non-mammalian vertebrates, vasotocin (VT) plays a role similar to mammalian VP, whereas mesotocin and isotocin are functionally similar to mammalian oxytocin (OT). Here, we review the involvement of VP in brain circuits, synaptic plasticity, evolution, and function, highlighting the role of VP in social behavior. In all studied species, VP is encoded on chromosome 20p13, and in mammals, VP is produced in specific hypothalamic nuclei and released by the posterior pituitary. The role of VP is mediated by the stimulation of the V1a, V1b, and V2 receptors as well as the oxytocinergic and purinergic receptors. VT and VP functions are usually related to osmotic and cardiovascular homeostasis when acting peripherally. However, these neuropeptides are also critically involved in the central modulation of social behavior displays, such as pairing recognition, pair-bonding, social memory, sexual behavior, parental care, and maternal and aggressive behavior. Evidence suggests that these effects are primarily mediated by V1a receptor in specific brain circuits that provide important information for the onset and control of social behaviors in normal and pathological conditions.

Gene expression in the CNS of lactating rats with different patterns of maternal behavior.

For most mammalian species, maternal behavior has an essential role in the development of the offspring. The frequency of licking/grooming (LG) the pups has been used as a parameter to evaluate maternal care, having mothers with high (HL) or low (LL) frequencies of LG. This study aimed to analyze the gene expression of the receptors for dopamine (Drd1a), prolactin (Prlr), serotonin (Htr1a, Htr1b), estrogen (Esr1, Esr2), and of Bdnf in the olfactory bulb (OB), hippocampus (HP), prefrontal cortex (PFC), and striatum (ST) of Wistar rats from three groups: LL (n = 8); HL (n = 8); virgin females in diestrus (D; n = 6). Maternal behavior was studied between the 1st and 7th postpartum days. Brain parts were analyzed by qRT-PCR. LL showed a decrease in the frequency of nursing, and an increase of remaining off the pups. There was an increase in gene expression of Drd1a, Prlr, Htr1a, Htr1b and Esr1 in the OB of HL, compared to LL. In the HP, Drd1a, Prlr and Htr1a were differently expressed when comparing HL, or LL, with D. The main finding is that HL had higher gene expression levels in the OB, which is a crucial structure to promote behavioral differences.

Transcriptional expression study in the central nervous system of rats: what gene should be used as internal control?

OBJECTIVE: A growing number of published articles report the expression of specific genes with different behavior patterns in rats. The levels of messenger ribonucleic acid transcripts are usually analyzed by reverse transcription followed by polymerase chain reaction and quantified after normalization with an internal control or reference gene (housekeeping gene). Nevertheless, housekeeping genes exhibit different expression in the central nervous system, depending on the physiological conditions and the area of the brain to be studied. The choice of a good internal control gene is essential for obtaining reliable results. This study evaluated the expression of three housekeeping genes (beta-actin, cyclophilin A, and ubiquitin C) in different areas of the central nervous system in rats (olfactory bulb, hippocampus, striatum, and prefrontal cortex). METHODS: Wistar rats (virgin females, n=6) during the diestrum period were used. Total ribonucleic acid was extracted from each region of the brain; the complementary deoxyribonucleic acid was synthesized by reverse transcription and amplified by real-time quantitative polymerase chain reaction using SYBR™ Green and primers specific for each one of the reference genes. The stability of the expression was determined using NormFinder. RESULTS: Beta-actin was the most stable gene in the hippocampus and striatum, while cyclophilin A and ubiquitin C showed greater stability in the prefrontal cortex and the olfactory bulb, respectively. CONCLUSION: Based on our study, further studies of gene expression using rats as animal models should take into consideration these results when choosing a reliable internal control gene.

Transcriptional expression study in the central nervous system of rats: what gene should be used as internal control? / Estudo de expressão transcricional no sistema nervoso central de ratos: qual gene deve ser usado como controle interno?

Objective A growing number of published articles report the expression of specific genes with different behavior patterns in rats. The levels of messenger ribonucleic acid transcripts are usually analyzed by reverse transcription followed by polymerase chain reaction and quantified after normalization with an internal control or reference gene (housekeeping gene). Nevertheless, housekeeping genes exhibit different expression in the central nervous system, depending on the physiological conditions and the area of the brain to be studied. The choice of a good internal control gene is essential for obtaining reliable results. This study evaluated the expression of three housekeeping genes (beta-actin, cyclophilin A, and ubiquitin C) in different areas of the central nervous system in rats (olfactory bulb, hippocampus, striatum, and prefrontal cortex). Methods Wistar rats (virgin females, n=6) during the diestrum period were used. Total ribonucleic acid was extracted from each region of the brain; the complementary deoxyribonucleic acid was synthesized by reverse transcription and amplified by real-time quantitative polymerase chain reaction using SYBR™ Green and primers specific for each one of the reference genes. The stability of the expression was determined using NormFinder. Results Beta-actin was the most stable gene in the hippocampus and striatum, while cyclophilin A and ubiquitin C showed greater stability in the prefrontal cortex and the olfactory bulb, respectively. Conclusion Based on our study, further studies of gene expression using rats as animal models should take into consideration these results when choosing a reliable internal control gene. .

Objetivo Um número crescente de artigos publicados relaciona a expressão de genes específicos com diferentes padrões de comportamento em ratos. Os níveis de transcritos de ácido ribonucleico mensageiro são geralmente analisados por transcrição reversa, seguida de reação em cadeia da polimerase, e quantificados após a normalização com um controle interno ou gene de referência (gene housekeeping). No entanto, os genes housekeeping exibem expressão diferencial no sistema nervoso central, dependendo das condições fisiológicas e da área do cérebro a ser estudada. A escolha de um bom gene de controle interno é essencial para a obtenção de resultados confiáveis. Este estudo avaliou a expressão de três genes housekeeping (beta-actina, ciclofilina A e ubiquitina C) em diferentes áreas do sistema nervoso central de ratos (bulbo olfatório, hipocampo, estriado e córtex pré-frontal). Métodos Foram usadas ratas Wistar (fêmeas virgens, n=6) durante o período de diestro. O ácido ribonucleico total foi extraído a partir de cada região do cérebro; o ácido desoxirribonucleico complementar foi sintetizado por transcrição reversa e amplificado por reação em cadeia da polimerase quantitativo em tempo real utilizando SYBR® Green e primers específicos para cada um dos genes de referência. A estabilidade de expressão foi determinada utilizando NormFinder. Resultados A beta-actina foi o gene mais estável no hipocampo e estriado, enquanto a ciclofilina A e a ubiquitina C apresentaram maior estabilidade no córtex pré-frontal e no bulbo olfatório, respectivamente. Conclusão Com base em nosso trabalho, estudos posteriores de expressão gênica utilizando ratos como modelos animais devem levar ...

Sexual behavior and dendritic spine density of posterodorsal medial amygdala neurons in oxytocin knockout female mice.

Central oxytocin (OT) and arginine-vasopressin (AVP) have been shown to play an important role in sexual behavior and neuroendocrine secretion in rodents. The results of exogenous OT administration on sexual behaviors in male and female mice are controversial. This study aimed to analyze the role of OT in sexual behavior, the number of oocytes and the density of dendritic spines in the posterodorsal medial amygdala (MePD) of female mice with selective deletion of the OT gene (OTKO). Female C57BL/6 mice were genotyped and divided into control (WT) and OTKO groups (n=11 each). All experiments were performed in the proestrus phase. Compared to WT data, our results showed that the OTKO group had a significant increase in the latency for the display of lordosis behavior (490.8 ± 113.8 and 841.9 ± 53.9, respectively) and a decrease in both the frequency (6.3 ± 2.4 and 0.5 ± 0.4) and duration (49.3 ± 19.9 and 7.2 ± 7.1) of lordosis and a reduction in the number of oocytes (12.2 ± 0.8 and 9.9 ± 0.6). However, the OTKO group showed a higher density of proximal dendritic spines in the MePD compared to the WT group (2.4 ± 0.1 and 1.9 ± 0.1 spines/dendritic µm, respectively). No significant difference was observed in the plasma levels of AVP between the groups (OTKO: 617.1 ± 96.0 and WT: 583.3 ± 112.0 pg/mL). Our data suggest that OT plays a crucial role in the sexual behavior display, number of released oocytes and density of dendritic spines in the MePD of female mice. The AVP plasma concentration was not affected in the OTKO animals.

Oxytocin modulates social interaction but is not essential for sexual behavior in male mice.

Recently, several studies have shown different conclusions regarding the effect of oxytocin (OT) on the social behaviors of male mice. Most of these studies used exogenous OT, but currently, investigations of the neural bases of social behavior are increasingly employing gene inactivation. This study aimed to analyze the role of OT in the modulation of social behaviors (i.e., sexual and social interaction behaviors) in male mice with selective deletions of the OT gene (OTKO) and the influence of this deletion in basal vasopressin (AVP) plasma concentrations. Our results showed that in the social interaction test, OTKO mice exhibited lower levels of social behaviors and higher levels of non-social behaviors compared to the wild type (WT) group. Additionally, the OTKO group showed a decrease in the number of agonistic behaviors delivered, and consequently, their dominance score was lower than that of the WT group. In the ethological analysis, the OTKO group had a lower aggressive performance and increased social investigation than the WT group. No significant differences were observed in the sexual behavior between groups. Finally, we found lower AVP plasma concentrations in the OTKO compared with the WT group. In conclusion, our data suggest that OT modulates social investigation behavior and the aggressiveness of male mice. The decrease in AVP concentrations in the OTKO group allows us to infer that AVP is physiologically relevant to these behavioral modulations. However, sexual behaviors do not seem to be affected by the lack of OT or by a decrease in the AVP concentration.

Analysis of transcriptional levels of the oxytocin receptor in different areas of the central nervous system and behaviors in high and low licking rats.

The natural variation in maternal care is an interesting model to analyze the physiological mechanisms that lead to differences in the mother-infant interaction. Several studies have shown differences in the expression of brain receptors such as the dopamine, estrogen and oxytocin receptors in areas classically involved in the onset and/or maintenance of maternal behavior: the medial preoptic area, the nucleus accumbens, the amygdala, the lateral septum, and the bed nucleus of the stria terminalis. The present study examined the responses of HL and LL rats in several behavioral tests and analyzes the transcription of the oxytocin receptor (OXTR) in the olfactory bulb (OB), the prefrontal cortex (FPC), the hippocampus (HP) and the striatum (ST) in different patterns of licking behavior. Our results showed that, in the second week postpartum, HL and LL mothers did not show behavioral differences in the elevated plus maze (EPM), the forced swimming test (FST) or the open field test. In the maternal aggressive behavior test, HL females showed a higher frequency of biting compared to LL females, but no significant differences in other aggressive behaviors were detected. LL mothers had higher levels of transcriptional OXTR in the OB and in the HP when compared to HL mothers. No differences in other areas were detected when compared LL and HL. These findings suggest that variations in maternal behavior may be associated with biting behavior of mothers and that OXTR participates in modulation of maternal behavior in rats, while other emotional behaviors are less related to such behavior.