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Comparative analysis among different species reveals that androgen receptor is a core transcriptional factor regulating the chicken follicular selection and ovulation [ChIP-Seq]

ABSTRACT: The differences of reproductive processes at molecular levels between the viviparous and oviparous animals are still unclear, and in the oviparous animal, the locations to synthetize sex hormones and also the trends to enrich sex hormones during follicle development are different from that of viviparous animals. To explore the commonalities (key factors for follicular development) and individualities (factors that cause differences among species) in the follicular development of viviparous and oviparous animals, we compared the similarities and differences in follicle development between viviparous and oviparous animals in terms of transcriptome and super-enhancer-based transcriptional regulation, using humans, bovines, and mice as representatives of viviparous animals and chickens, for oviparous animals. It was found that follicle development in molecular terms tended to be more conservative between viviparous and oviparous animals. Estrogen receptors and androgen receptors occupied central positions in the transcriptional regulatory networks of viviparous and oviparous animals respectively, which may be related with differences in the synthesis and secretion of sex hormones between oviparous and viviparous animals. The role of androgen receptors in chicken follicle development was verified through cell level and field experiments. Our study would facilitate to extend existing results of follicle development in viviparous animals to oviparous animals, and our results emphasized the importance of the androgen receptor in chicken follicle development. Comparative analysis among different species in follicle development will help us to gain insight on the mechanisms of follicle development.

ORGANISM(S): Gallus gallus

PROVIDER: GSE163889 | GEO | 2021/02/28

REPOSITORIES: GEO

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Project description:The differences in reproductive processes at the molecular level between viviparous and oviparous animals are evident, and the site in the ovary that synthesizes sex hormones (androgens and oestrogens) and the trends for enriching sex hormones during follicle development in chickens are different from those in mammals, suggesting that the effect of sex hormones on follicle development in chickens is probably different from that in viviparous animals. To explore the specific role of androgen receptors (ARs) on chicken follicular development, we matched the correspondence of follicular development stages among chickens, humans, cows and identified chicken-specific genes related to follicle development (GAL-SPGs) by comparing follicle development-related genes and their biological functions among species (chickens, humans, and cows). A comparison of the core transcription factor regulatory network of granulosa cells (or ovaries) based on super enhancers among species (chicken, human, and mouse) revealed that AR is a core transcriptional regulator specific to chickens. In vivo experiments showed that inhibition of AR significantly reduced the number of syf (selected stage follicles) in chickens and decreased the expression of GAL-SPGs in F5 follicles, while in vitro experiments showed that inhibition of AR expression in chicken granulosa cells (GCs) significantly down-regulated the expression levels of GAL-SPGs, indicating that AR could regulate follicle selection through chicken-specific genes related to follicle development. A comparison among species (77 vertebrates) of the conserved genomic regions, where chicken super-enhancers are located, revealed that the chicken AR super-enhancer region is conserved in birds, suggesting that the role of AR in follicle selection may be widespread in birds. In summary, we found that AR can regulate follicle selection through chicken-specific genes related to follicle development, which also emphasizes the important role of AR in follicle selection in chickens and provides a new perspective for understanding the unique process of follicle development in chickens.

Project description:Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology and activity, synapse molecular organization, synaptic plasticity, and molecular signalling pathways. Among different processes assuring proper synapse function are posttranslational modifications, and among them, S-palmitoylation emerges as a crucial mechanism underlying synaptic integrity. Protein S-palmitoylation (S-PALM) refers to the covalent attachment of palmitic acid (C16:0) to cysteine residue(s) via the formation of a thioester bond. Protein S-PALM is governed by a family of PATs, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase. Under physiological conditions, DHHC7 emerges of particular interest because it palmitoylates various synaptic proteins involved in the regulation of cellular polarity and proliferation as well as in stress and anxiety-related pathology. Moreover, DHHC7 is responsible for S-PALM of sex steroid receptors. Functionally, S-PALM of these receptors regulates their trafficking to the plasma membrane as well as their rapid responses to sex steroid hormones. Using mass spectrometry-based method PANIMoni we identified sex-dependent differences in the S-palmitoylation of synaptic proteins, potentially involved in the regulation of passive membrane properties and excitability (e.g. potassium voltage-gated channels), synaptic transmission (e.g. subunits of glutamate or kainate receptors, voltage-dependent calcium channels) as well as signalling proteins involved in structural plasticity of dendritic spines (e.g. G-proteins and Rab GTPase). Furthermore, to determine a mechanistic source for sex-dependent changes in protein S-palmitoylation we used synaptoneurosomes from DHHC-7 knock-out -/- (DHHC7 KO) female and male mice. Our data showed sex-dependent action of DHHC-7 acyltransferase. Such discovery will facilitate the development of novel and targeted treatments congruous with biological sex.

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Comparative analysis among different species reveals that androgen receptor is a core transcriptional factor regulating the chicken follicular selection and ovulation [ChIP-Seq]

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