Biology subjects

Calisi, R. M.

Publications and source records attributed to Calisi, R. M..

5 recordsLinked to original sources

bioRxiv2021

Prolactin maintains parental responses and alters reproductive axis gene expression, but not courtship behaviors, in both sexes of a biparental bird

Prolactin, a hormone involved in vertebrate parental care, is hypothesized to inhibit reproductive hypothalamic-pituitary-gonadal (HPG) axis activity during parenting, thus maintaining investment in the current brood as opposed to new reproductive efforts. While prolactin underlies many parental behaviors in birds, its effects on other reproductive behaviors, such as courtship, remain unstudied. How prolactin affects neuropeptide and hormone receptor expression across the avian HPG axis also remains unknown. To address these questions, we administered ovine prolactin (oPRL) or a vehicle control to both sexes in experienced pairs of the biparental rock dove (Columba livia), after nest removal at the end of incubation. We found that oPRL promoted parental responses to novel chicks and stimulated crop growth compared to controls, consistent with other studies. However, we found that neither courtship behaviors, copulation rates nor pair maintenance differed with oPRL treatment. Across the HPG, we found oPRL had little effect on gene expression in hypothalamic nuclei, but increased expression of FSHB and hypothalamic hormone receptor genes in the pituitary. In the gonads, oPRL increased testes size and gonadotropin receptor expression, but did not affect ovarian state or small white follicle gene expression. However, the oviducts of oPRL-treated females were smaller and had lower estrogen receptor expression compared with controls. Our results highlight that some species, especially those that show multiple brooding, may be able to maintain mating behavior despite elevated prolactin. Thus, mechanisms may exist for prolactin to promote investment in parental care without concurrent inhibition of reproductive function or HPG axis activity.

animal behavior and cognition↗

bioRxiv2021

Prolactin and prolactin receptor expression in the HPG axis and crop sac during parental care in both sexes of a biparental bird (Columba livia)

During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary-gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.

animal behavior and cognition↗

bioRxiv2020

Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response

The negative impacts of stress on reproduction have long been studied. A large focus of investigation has centered around the effects of the adrenal steroid hormone corticosterone (CORT) on a system of tissues vital for reproduction, the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Investigations of the role of CORT on the HPG axis have predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT, characteristic of the stress response, affects the activity of the HPG axis, we experimentally examined its role at the level of the genome in both male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating corticosterone in vertebrates. We examined all changes in genomic transcription within the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls, as well as between the sexes. We report causal and sex-specific effects of CORT on the HPG stress response at the level of the transcriptome. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects who underwent restraint stress and those who were given exogenous CORT. In response to CORT elevation characteristic of the stress response, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. These results provide novel targets for new lines of further investigation and therapy development. We present an extensive and openly accessible view of the role corticosterone in the HPG genomic stress response, offering novel gene targets to inspire new lines of investigation of stress-induced reproductive dysfunction. Because the HPG system is well-conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

physiology↗

bioRxiv2019

Stress-mediated convergence of splicing landscapes in male and female Rock Doves

BackgroundThe process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothlamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.\n\nResultsThis study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, post submitting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3UTR end of transcripts than the 5UTR or coding regions.\n\nConclusionsOur results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.

genomics↗

bioRxiv2016

Transcriptomics reveals patterns of sexually dimorphic gene expression in an avian hypothalamic-pituitary-gonadal (HPG) axis

The hypothalamic-pituitary-gonadal (HPG) axis is a key biological system required for reproduction and associated sexual behaviors to occur. Each of these tissues, the hypothalamus in the brain, the pituitary gland, and the gonads (testes and ovaries), has specialized and sometimes sex-specific functions that promote, amongst other things, reproductive processes. To fully characterize the transcript community of each aspect of the HPG axis, as well as to uncover potentially important sex-specific differences, we characterized patterns of gene expression in sexually mature male and female rock dove (Columba livia) hypothalamus, pituitary, and gonads. We describe patterns of gene expression amongst tissues as well as patterns of sex-biased gene expression which may underlie some of the fundamental differences between male and female reproductive behavior. We report greater sex-biased differential expression in the pituitary (233 genes out of 15,102 genes) as compared to the hypothalamus (1 gene out of 15,102 genes), with multiple genes overexpressed in the male pituitary gland being related to locomotion, and multiple genes over-expressed in the female pituitary gland being related to reproduction, growth and development. These genes may be associated with facilitating the different roles the HPG system plays in sex-specific reproductive behavior, including life-history strategies characterized by short-term payoffs in males (i.e. locomotion) and longer-term payoffs in females (i.e. development and reproduction). In addition, we report novel patterns of sex-biased expression in genes involved in reproduction-associated processes. Gonadotropin-releasing hormone, Progesterone, and Androgen receptor were upregulated in the female pituitary as compared to the male pituitary. We also found greater expression of Prolactin in the female pituitary as compared to the male pituitary, but it was more highly expressed in the male hypothalamus as compared to the female hypothalamus. The Prolactin receptor was also more highly expressed in the male hypothalamus and pituitary gland as compared to corresponding female tissues. Finally, we discovered greater expression of Arginine Vasopressin Receptor 1A in the male pituitary as compared to the female pituitary. Using a more global analysis, we discovered other interesting sex-biased patterns in genes not originally targeted for investigation. These genes include like Betacellulin (BTC), which was upregulated in the female pituitary and compared to males, and Ecto-NOX Disulfide-Thiol Exchanger 1 (ENOX1), which was upregulated in the male pituitary as compared to females. These genes may play important, though currently unknown, roles in reproductive physiology and behavior. In conclusion, we reveal patterns of tissue specific and sexually dimorphic gene expression in the HPG axis, highlighting the need for sex parity in transcriptomic studies and providing new lines of investigation of the mechanisms of reproductive function.

neuroscience↗