Authors: Constantina Theofanopoulou

Vertebrate genome evolution remains a hotly debated topic, specifically as regards the number and the timing of putative rounds of whole genome duplication events. In this study, I sought to shed light to this conundrum through assessing the evolutionary history of the oxytocin/vasotocin receptor family. I performed ancestral analyses of the genomic segments containing oxytocin and vasotocin receptors (OTR-VTRs) by mapping them back to the reconstructed ancestral vertebrate/chordate karyotypes reported in five independent studies (Nakatani et al., 2007; Putnam et al., 2008; Smith and Keinath, 2015; Smith et al., 2018; Simakov et al., 2020) and found that two alternative scenarios can account for their evolution: one consistent with one round of whole genome duplication in the common ancestor of lampreys and gnathostomes, followed by segmental duplications in both lineages, and another consistent with two rounds of whole genome duplication, with the first occurring in the gnathostome-lamprey ancestor and the second in the jawed vertebrate ancestor. Combining the data reported here with synteny and phylogeny data reported in our previous study (Theofanopoulou et al., 2021), I put forward that a single round of whole genome duplication scenario is more consistent with the synteny and evolution of chromosomes where OTR-VTRs are encountered, without excluding the possibility of a scenario including two rounds of whole genome duplication. Although the analysis of one gene family is not able to capture the full complexity of vertebrate genome evolution, this study can provide solid insight, since the gene family used here has been meticulously analyzed for its genes' orthologous and paralogous relationships across species using high quality genomes.

Topics: Animals; Biological Evolution; Databases, Genetic; Evolution, Molecular; Gene Duplication; Gene Expression; Gene Expression Regulation; Genome; Humans; Oxytocin; Phylogeny; Receptors, Oxytocin; Receptors, Vasopressin; Vasotocin

PubMed: 34329619
DOI: 10.1016/j.ydbio.2021.07.012

Authors: Li Kang Lyu, Jian Shuang Li, Xiao Jie Wang...

Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies () were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis isotocin (IT) receptors (ITRs). One copy each of and and two copies of were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10, 10, and 10 mol/L) significantly activated (P < 0.05). experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (), which is the rate-limiting enzyme involved in PG biosynthesis, and by AVT and IT. Furthermore, dual hybridization detected positive signals for and at the same site, implying that ITR1 may regulate gene expression. Measurement of prostaglandin F (PGF) concentrations showed that AVT induced PGF synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis ITR and that PGF induces delivery behavior in ovoviviparous guppies.

Topics: Animals; Behavior, Animal; Cyclooxygenase 2; Dinoprost; Oxytocin; Parturition; Poecilia; Receptors, Vasopressin; Up-Regulation; Vasotocin

PubMed: 33967951
DOI: 10.3389/fendo.2021.617580

Authors: Constantina Theofanopoulou, Gregory Gedman, James A Cahill...

Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; hereafter VT) are neurotransmitter ligands that function through specific receptors to control diverse functions. Here we performed genomic analyses on 35 species that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project. Our findings support the claim that OT (also known as OXT) and VT (also known as AVP) are adjacent paralogous genes that have resulted from a local duplication, which we infer was through DNA transposable elements near the origin of vertebrates and in which VT retained more of the parental sequence. We identified six major oxytocin-vasotocin receptors among vertebrates. We propose that all six of these receptors arose from a single receptor that was shared with the common ancestor of invertebrates, through a combination of whole-genome and large segmental duplications. We propose a universal nomenclature based on evolutionary relationships for the genes that encode these receptors, in which the genes are given the same orthologous names across vertebrates and paralogous names relative to each other. This nomenclature avoids confusion due to differential naming in the pre-genomic era and incomplete genome assemblies, furthers our understanding of the evolution of these genes, aids in the translation of findings across species and serves as a model for other gene families.

Topics: Animals; Evolution, Molecular; Gene Duplication; Ligands; Multigene Family; Oxytocin; Phylogeny; Receptors, Oxytocin; Receptors, Vasopressin; Synteny; Terminology as Topic; Vasotocin; Vertebrates

PubMed: 33911268
DOI: 10.1038/s41586-020-03040-7

Authors: Sean C Lema, Elsie H Washburn, Mary E Crowley...

The nonapeptide arginine vasotocin (AVT) regulates osmotic balance in teleost fishes, but its mechanisms of action are not fully understood. Recently, it was discovered that nonapeptide receptors in teleost fishes are differentiated into two V1a-type, several V2-type, and two isotocin (IT) receptors, but it remains unclear which receptors mediate AVT's effects on gill osmoregulation. Here, we examined the role of nonapeptide receptors in the gill of the euryhaline Amargosa pupfish () during osmotic acclimation. Transcripts for the teleost V1a-type receptor were upregulated over fourfold in gill 24 h after transferring pupfish from 7.5 ppt to seawater (35 ppt) or hypersaline (55 ppt) conditions and downregulated after transfer to freshwater (0.3 ppt). Gill transcripts for the nonapeptide degradation enzyme leucyl-cystinyl aminopeptidase (LNPEP) also increased in fish acclimating to 35 ppt. To test whether the effects of AVT on the gill might be mediated by a V1a-type receptor, we administered AVT or a V1-type receptor antagonist (Manning compound) intraperitoneally to pupfish before transfer to 0.4 ppt or 35 ppt. Pupfish transferred to 35 ppt exhibited elevated gill mRNA abundance for cystic fibrosis transmembrane conductance regulator (), but that upregulation diminished under V1-receptor inhibition. AVT inhibited the increase in gill Na/Cl cotransporter 2 () transcript abundance that occurs following transfer to hypoosmotic environments, whereas V1-type receptor antagonism increased mRNAs even without a change in salinity. These findings indicate that AVT acts via a V1-type receptor to regulate gill Cl transport by inhibiting Cl uptake and facilitating Cl secretion during seawater acclimation.

Topics: Animals; Cystic Fibrosis Transmembrane Conductance Regulator; Cystinyl Aminopeptidase; Female; Fish Proteins; Gills; Killifishes; Male; Osmoregulation; Oxytocin; Receptors, Vasopressin; Salinity; Salt Tolerance; Seawater; Signal Transduction; Solute Carrier Family 12, Member 1; Up-Regulation; Vasotocin

PubMed: 30916577
DOI: 10.1152/ajpregu.00328.2018

Authors: Rashmi Srivastava, Lawrence E Cornett, Chandra Mohini Chaturvedi...

Role of estrogen and photoperiod is well-established in avian reproduction. In addition, the distribution and the expression of arginine vasotocin (AVT) and its receptor VT3 to ensure reproductive/breeding conditions in Japanese quail influenced by them has been the main focus of this review. To consider this aspect the mRNA expression of VT3 receptor and its ligand AVT in the shell gland has been emphasized. In birds, AVT performs a dual role as an anti-diuretic hormone and the functions accomplished by oxytocin in mammals. The physiological actions of AVT in birds are mediated through its diverse receptor subtypes VT1, VT2, VT3 and VT4.  Dynamic alteration of VT3 expression during different reproductive and photo-sexual conditions of quail can be modulated by estrogen. In addition to the endocrine effect of AVT, the shell gland is complemented by its paracrine action via its receptors. Evidences indicate that the expression of shell gland AVT modulated by estrogen appears to play a priming role by modulating the availability of VT3 receptor for the required action of neurohypophysial AVT during oviposition.

Topics: Animals; Coturnix; Estrogens; Female; Oviposition; Oxytocin; Photoperiod; Quail; Receptors, Vasopressin; Reproduction; Tamoxifen; Vasopressins; Vasotocin

PubMed: 29772564
DOI: 10.2741/S522

Corticosterone suppresses vasotocin-enhanced clasping behavior in male rough-skinned newts by novel mechanisms interfering with V1a receptor availability and receptor-mediated endocytosis.

Authors: Audrey Davis, Emily Abraham, Erin McEvoy...

In rough-skinned newts, Taricha granulosa, exposure to an acute stressor results in the rapid release of corticosterone (CORT), which suppresses the ability of vasotocin (VT) to enhance clasping behavior. CORT also suppresses VT-induced spontaneous activity and sensory responsiveness of clasp-controlling neurons in the rostromedial reticular formation (Rf). The cellular mechanisms underlying this interaction remain unclear. We hypothesized that CORT blocks VT-enhanced clasping by interfering with V1a receptor availability and/or VT-induced endocytosis. We administered a physiologically active fluorescent VT conjugated to Oregon Green (VT-OG) to the fourth ventricle 9 min after an intraperitoneal injection of CORT (0, 10, 40 μg/0.1mL amphibian Ringers). The brains were collected 30 min post-VT-OG, fixed, and imaged with confocal microscopy. CORT diminished the number of endocytosed vesicles, percent area containing VT-OG, sum intensity of VT-OG, and the amount of VT-V1a within each vesicle; indicating that CORT was interfering with V1a receptor availability and VT-V1a receptor-mediated endocytosis. CORT actions were brain location-specific and season-dependent in a manner that is consistent with the natural and context-dependent expression of clasping behavior. Furthermore, the sensitivity of the Rf to CORT was much higher in animals during the breeding season, arguing for ethologically appropriate seasonal variation in CORT's ability to prevent VT-induced endocytosis. Our data are consistent with the time course and interaction effects of CORT and VT on clasping behavior and neurophysiology. CORT interference with VT-induced endocytosis may be a common mechanism employed by hormones across taxa for mediating rapid context- and season-specific behavioral responses.

Topics: Animals; Brain; Corticosterone; Down-Regulation; Endocytosis; Male; Neurons; Receptors, Vasopressin; Reticular Formation; Salamandridae; Sexual Behavior, Animal; Signal Transduction; Vasotocin

PubMed: 25528549
DOI: 10.1016/j.yhbeh.2014.12.006

Authors: Nicole M Baran, Nathan C Sklar, Elizabeth Adkins-Regan...

Zebra finches demonstrate selective affiliation between juvenile offspring and parents, which, like affiliation between pair partners, is characterized by proximity, vocal communication and contact behaviors. This experiment tested the hypothesis that the nonapeptide arginine vasotocin (AVT, avian homologue of vasopressin) and nonapeptide receptors play a role prior to fledging in the development of affiliative behavior. Zebra finch hatchlings of both sexes received daily intracranial injections (post-hatch days 2-8) of either AVT, Manning Compound (MC, a potent V1a receptor antagonist) or saline (vehicle control). The social development of both sexes was assessed by measuring responsiveness to isolation from the family and subsequent reunion with the male parent after fledging. In addition, we assessed the changes in affiliation with the parents, unfamiliar males, and unfamiliar females each week throughout juvenile development. Compared to controls, MC subjects showed decreased attachment to the parents and MC males did not show the normal increase in affiliative interest in opposite sex individuals as they reached reproductive maturity. In contrast, AVT subjects showed a sustained affiliative interest in parents throughout development, and males showed increased interest in opposite sex conspecifics as they matured. These results provide the first evidence suggesting that AVT and nonapeptide receptors play organizational roles in social development in a bird.

Topics: Aggression; Aging; Animals; Behavior, Animal; Female; Finches; Growth and Development; Hierarchy, Social; Hormone Antagonists; Male; Play and Playthings; Social Behavior; Vasopressins; Vasotocin

PubMed: 26476409
DOI: 10.1016/j.yhbeh.2015.10.005

Authors: Juan Antonio Martos-Sitcha, Marco Antonio Campinho, Juan Miguel Mancera...

Aquaporins (AQPs) are specific transmembrane water channels with an important function in water homeostasis. In terrestrial vertebrates, AQP2 function is regulated by vasopressin (AVP) to accomplish key functions in osmoregulation. The endocrine control of aquaporin function in teleosts remains little studied. Therefore, in this study we investigated the regulatory role of vasotocin (AVTR) and isotocin (ITR) receptors in Aqp1 paralog gene function in the teleost gilthead sea bream (Sparus aurata). The complete coding regions of Aqp1a, Aqp1b, AVTR V1a2-type, AVTR V2-type and ITR from sea bream were isolated. A Xenopus oocyte-swelling assay was used to functionally characterize AQP1 function and regulation by AVT and IT through their cognate receptors. Microinjection of oocytes with Aqp1b mRNA revealed regulation of water transport via PKA (IBMX+forskolin sensitive), whereas Aqp1a mRNA injection had the same effect via PKC signaling (PDBU sensitive). In the absence of expressed receptors, AVT and IT (10(-8) mol l(-1)) were unable to modify AQP1 function. AVT regulated AQP1a and AQP1b function only when the AVTR V2-type was co-expressed. IT regulated AQP1a function, but not AQP1b, only when ITR was present. Considering that Aqp1a and Aqp1b gene expression in the sea bream intestine is highly salinity dependent in vivo, our results in ovo demonstrate a regulatory role for AVT and IT in AQP1 function in the sea bream in the processing of intestinal fluid to achieve osmoregulation.

Topics: Animals; Aquaporin 1; Cell Size; Female; Gene Expression Regulation; Male; Oocytes; Osmoregulation; Oxytocin; RNA, Messenger; Receptors, Vasopressin; Salinity; Sea Bream; Vasotocin; Xenopus laevis

PubMed: 25573823
DOI: 10.1242/jeb.114546

Authors: Saori Yokoi, Teruhiro Okuyama, Yasuhiro Kamei...

To increase individual male fitness, males of various species remain near a (potential) mating partner and repel their rivals (mate-guarding). Mate-guarding is assumed to be mediated by two different types of motivation: sexual motivation toward the opposite sex and competitive motivation toward the same sex. The genetic/molecular mechanisms underlying how mate presence affects male competitive motivation in a triadic relationship has remained largely unknown. Here we showed that male medaka fish prominently exhibit mate-guarding behavior. The presence of a female robustly triggers male-male competition for the female in a triadic relationship (2 males and 1 female). The male-male competition resulted in one male occupying a dominant position near the female while interfering with the other male's approach of the female. Paternity testing revealed that the dominant male had a significantly higher mating success rate than the other male in a triadic relationship. We next generated medaka mutants of arginine-vasotocin (avt) and its receptors (V1a1, V1a2) and revealed that two genes, avt and V1a2, are required for normal mate-guarding behavior. In addition, behavioral analysis of courtship behaviors in a dyadic relationship and aggressive behaviors within a male group revealed that avt mutant males displayed decreased sexual motivation but showed normal aggression. In contrast, heterozygote V1a2 mutant males displayed decreased aggression, but normal mate-guarding and courtship behavior. Thus, impaired mate-guarding in avt and V1a2 homozygote mutants may be due to the loss of sexual motivation toward the opposite sex, and not to the loss of competitive motivation toward rival males. The different behavioral phenotypes between avt, V1a2 heterozygote, and V1a2 homozygote mutants suggest that there are redundant systems to activate V1a2 and that endogenous ligands activating the receptor may differ according to the social context.

Topics: Aggression; Animals; Copulation; Female; Male; Marriage; Motivation; Oryzias; Reproduction; Sexual Behavior, Animal; Vasotocin

PubMed: 25719383
DOI: 10.1371/journal.pgen.1005009

Authors: J A Martos-Sitcha, J Fuentes, J M Mancera...

The dynamic changes in mRNA expression levels for vasotocin (AVT) and isotocin (IT) receptor gene levels were assessed in a time-course response study in immature male specimens of the gilthead sea bream (Sparus aurata) submitted to hyper- (55‰ salinity) and hypo-osmotic (5‰ salinity) challenges. Two different cDNAs for the AVT receptor and one for the IT receptor (V1a2-type and V2-type AVTR, and ITR, respectively) were cloned by screening an S. aurata brain cDNA library. Genes for these receptors were expressed differentially and is nearly ubiquitously in 26 of the examined tissues. In the gills, both environmental salinity challenges up-regulated AVTR V1a2-type gene expression concomitantly with mRNA expression protein activity of Na(+), K(+)-ATPase gene expression and protein, whereas the AVTR V2-type and cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels were associated with mRNAs environmental salinity, indicating a possible connection between AVTRs and these transporters. In kidney, AVTR V1a2-type gene expression peaked rapidly and lasted only a short time (12-24h) in response to both osmotic challenges. In contrast, AVTR V2-type mRNA levels were enhanced in specimens exposed to hyperosmotic conditions, whereas they decreased under hypoosmotic environments, suggesting an antidiuretic role related to the vasoconstriction function. In the hypothalamus, only the expression of the AVTR V2-type gene was enhanced at 7 and 14 days under both experimental conditions. In the liver, both AVTRs had increased mRNA levels, with the upregulation of their AVTR V2-type gene increasing faster than the V1a2-type. The ITR gene was not sensitive to variations of external salinity in any of the analyzed tissues. Our results demonstrate the involvement of the vasotocinergic, but not the isotocinergic, pathway as well as the hypothalamic function, in the adjustments of both osmoregulatory and metabolic processes after osmotic challenges.

Topics: Amino Acid Sequence; Animals; Base Sequence; DNA, Complementary; Gene Expression Regulation; Gills; Hypothalamus; Liver; Male; Molecular Sequence Data; Osmoregulation; Osmotic Pressure; Oxytocin; Phylogeny; RNA, Messenger; Receptors, Vasopressin; Salinity; Sea Bream; Vasotocin

PubMed: 24332959
DOI: 10.1016/j.ygcen.2013.11.026