The Regulation of Gonadal Somatic Cell Differentiation in Humans

Chen, Min; Gao, Fei

doi:10.1016/j.gpb.2022.04.003

Cited by 5 publications

(7 citation statements)

References 25 publications

(35 reference statements)

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“…Moreover, a proper interaction between germ cells and gonadal somatic cells is not only crucial for gonads but also for gene regulation in the brain. 4. This study revealed the key genes and neural signaling pathways of different brain regions that are involved in modulating brain dimorphism and male mating behavior in zebrafish.…”

Section: Highlightsmentioning

confidence: 90%

“…Although the role of germ cells in sexual differentiation has been widely studied among species, little is known about the influence of germ cells on the formation of SSCs and sexual behaviors. In most animals, gonadal sex is determined by signals from the somatic cells, such as mice [4]; however, there is no evidence on whether the complete loss of germ cells could affect the formation of SSCs and sexual behaviors. Zebrafish gonadal sex differentiation is mainly under the control of multiple genes and the number of germ cells [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish Gonad Mutant Models Reveal Neuroendocrine Mechanisms of Brain Sexual Dimorphism and Male Mating Behaviors of Different Brain Regions

Dai

Pradhan

Liu

et al. 2023

Preprint

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Background: Sexually dimorphic mating behaviors differ between sexes and involve gonadal hormones and possibly sexually dimorphic gene expression in the brain. However, the associations among the brain, gonad, and sexual behavior in teleosts are still unclear. Here, we utilized germ cells-free tdrd12 knockout (KO) zebrafish, and steroid synthesis enzyme cyp17a1-deficient zebrafish to investigate the differences and interactions in the brain-gonad-behavior axis, and the molecular control of brain dimorphism and male mating behaviors. Methods: Tdrd12+/-; cyp17a1+/- double heterozygous parents were crossed to obtain tdrd12-/-;cyp17a1+/+ (tdrd12 KO), tdrd12+/+;cyp17a1-/- (cyp17a1 KO), and tdrd12-/-;cyp17a1-/- (double KO) homozygous progenies. Comparative analysis of mating behaviors were evaluated by using Viewpoint zebrafish tracking software and sexual traits were thoroughly characterized based on anatomical and histological experiments in these KOs and wide-types. The steroid hormone levels (testosterone, 11-ketotestosterone and estrogen) in the brains, gonads, and serum were measured using ELISA kits. To achieve a higher-resolution view of the diﬀerences in region-specific expression patterns of the brain, the brains of these KOs, and control male and female fish were dissected into three regions: the forebrain, midbrain, and hindbrain for transcriptomic analysis. Results: Qualitative analysis of mating behaviors demonstrated that tdrd12-/- fish behaved in the same manner as wild-type males to trigger oviposition behavior, while cyp17a1-/- and double knockout (KO) fish did not exhibit these behaviors. Based on the observation of sex characteristics, mating behaviors and hormone levels in these mutants, we found that the maintenance of secondary sex characteristics and male mating behavior did not depend on the presence of germ cells; rather, they depended mainly on the 11-ketotestosterone and testosterone levels secreted into the brain-gonad-regulatory axis. RNA-seq analysis of different brain regions revealed that the brain transcript profile of tdrd12-/- fish was similar to that of wild-type males, especially in the forebrain and midbrain. However, the brain transcript profiles of cyp17a1-/- and double KO fish were distinct from those of wild-type males and were partially biased towards the expression pattern of the female brain. Our results revealed key genes and signaling pathways, such as synaptic signaling/neurotransmission, MAPK signaling, and steroid hormone pathways, that shape brain dimorphism and modulate male mating behavior in zebrafish. Conclusions: Our results provide comprehensive analyses and new insights regarding the endogenous interactions in the brain-gonad-behavior axis. Moreover, this study revealed the key genes and neural signaling pathways of different brain regions that are involved in modulating brain dimorphism and male mating behavior in zebrafish, which would significantly light up the understanding the neuroendocrine and molecular mechanisms modulating brain dimorphism and male mating behavior in zebrafish and other teleost fish.

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Section: Highlightsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Zebrafish Gonad Mutant Models Reveal Neuroendocrine Mechanisms of Brain Sexual Dimorphism and Male Mating Behaviors of Different Brain Regions

Dai

Pradhan

Liu

et al. 2023

Preprint

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“…During mouse embryonic development between 10.5 and 12.5 dpc, when the genital ridge remains undifferentiated, SRY is temporarily expressed in XY embryos, which peaks at approximately 11.5 dpc ( 51 ). Consequently, SOX9 is rapidly translocated from the cytoplasm to the nucleus.…”

Section: Role Of Sertoli Cell Lineage Differentiation In Male Sex Det...mentioning

confidence: 99%

“…If either SRY or SOX9 activation fails to occur, the development of granulosa cells and ovarian pathways is initiated instead ( 57 , 58 ). The expression of SOX9 also enhances the expression of testicular development-related factors, such as prostaglandin D2 synthase ( PTGDS ), anti-Müllerian hormone ( AMH ), WT1 , GATA4 , and ex-determining region Y-box 8 ( SOX8 ), while concurrently inhibiting the expression of ovarian determinants, including WNT4 , R-spondin 1 ( RSPO1 ), and β-catenin ( 51 , 54 , 59 ). Moreover, SOX9 can further enhance its own expression by activating the PGD2 and fibroblast growth factor 9 (FGF9) signaling pathways ( 60 ), thereby forming a positive feedback loop ( 51 ).…”

Section: Role Of Sertoli Cell Lineage Differentiation In Male Sex Det...mentioning

confidence: 99%

Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review

Gao,

Wang,

Long

et al. 2024

Front. Endocrinol.

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In mammals, gonadal somatic cell lineage differentiation determines the development of the bipotential gonad into either the ovary or testis. Sertoli cells, the only somatic cells in the spermatogenic tubules, support spermatogenesis during gonadal development. During embryonic Sertoli cell lineage differentiation, relevant genes, including WT1, GATA4, SRY, SOX9, AMH, PTGDS, SF1, and DMRT1, are expressed at specific times and in specific locations to ensure the correct differentiation of the embryo toward the male phenotype. The dysregulated development of Sertoli cells leads to gonadal malformations and male fertility disorders. Nevertheless, the molecular pathways underlying the embryonic origin of Sertoli cells remain elusive. By reviewing recent advances in research on embryonic Sertoli cell genesis and its key regulators, this review provides novel insights into sex determination in male mammals as well as the molecular mechanisms underlying the genealogical differentiation of Sertoli cells in the male reproductive ridge.

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“…The interaction between PGCs and surrounding granulosa cells highly affects the growth and differentiation of both cell types. To better understand the time-dependent interaction among follicular cells, single cell RNA-sequencing was used to elucidate the trajectory and crucial signalling pathways for pre-GC differentiation in mouse and human ovarian cells ( Stévant et al, 2019 ; Niu and Spradling, 2020 ; Wang et al, 2020 ; Fukuda et al, 2021 ; Chen and Gao, 2022 ; Garcia-Alonso et al, 2022 ). Not until recently, by following the developmental trajectory, the protocol for deriving foetal ovarian somatic cell-like cells (FOSLCs) from mESCs was reported ( Figure 3 ).…”

Section: Current Progress On In-vitro Differentiat...mentioning

confidence: 99%

Current progress on in vitro differentiation of ovarian follicles from pluripotent stem cells

Chen

Yeung

et al. 2023

Front. Cell Dev. Biol.

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Mammalian female reproduction requires a functional ovary. Competence of the ovary is determined by the quality of its basic unit–ovarian follicles. A normal follicle consists of an oocyte enclosed within ovarian follicular cells. In humans and mice, the ovarian follicles are formed at the foetal and the early neonatal stage respectively, and their renewal at the adult stage is controversial. Extensive research emerges recently to produce ovarian follicles in-vitro from different species. Previous reports demonstrated the differentiation of mouse and human pluripotent stem cells into germline cells, termed primordial germ cell-like cells (PGCLCs). The germ cell-specific gene expressions and epigenetic features including global DNA demethylation and histone modifications of the pluripotent stem cells-derived PGCLCs were extensively characterized. The PGCLCs hold potential for forming ovarian follicles or organoids upon cocultured with ovarian somatic cells. Intriguingly, the oocytes isolated from the organoids could be fertilized in-vitro. Based on the knowledge of in-vivo derived pre-granulosa cells, the generation of these cells from pluripotent stem cells termed foetal ovarian somatic cell-like cells was also reported recently. Despite successful in-vitro folliculogenesis from pluripotent stem cells, the efficiency remains low, mainly due to the lack of information on the interaction between PGCLCs and pre-granulosa cells. The establishment of in-vitro pluripotent stem cell-based models paves the way for understanding the critical signalling pathways and molecules during folliculogenesis. This article aims to review the developmental events during in-vivo follicular development and discuss the current progress of generation of PGCLCs, pre-granulosa and theca cells in-vitro.

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The Regulation of Gonadal Somatic Cell Differentiation in Humans

Cited by 5 publications

References 25 publications

Zebrafish Gonad Mutant Models Reveal Neuroendocrine Mechanisms of Brain Sexual Dimorphism and Male Mating Behaviors of Different Brain Regions

Zebrafish Gonad Mutant Models Reveal Neuroendocrine Mechanisms of Brain Sexual Dimorphism and Male Mating Behaviors of Different Brain Regions

Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review

Current progress on in vitro differentiation of ovarian follicles from pluripotent stem cells

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