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Molecular and cellular design of ovotestis development

ABSTRACT: Ovotestis often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains unknown. Here, we report the first comprehensive single-cell developmental atlas of the model fish ovotestis. We provide an overview of ovotestis cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by developmental defects in oogenesis owing to dynamic autophagic degradation in female germline cells, and in spermatogenesis due to deficiency of histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germline cells synergistically determined cell fates of both male and female germlines in ovotestis. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation directions of ovotestis, and provide novel insights into ovotestis development.

ORGANISM(S): Monopterus albus

PROVIDER: GSE153961 | GEO | 2021/04/21

REPOSITORIES: GEO

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Project description:The nuclear receptor subfamily 5 group A member 1 (NR5A1), encoding steroidogenic factor 1 (SF-1), has been identified as a critical factor in gonadal development in animal studies. A previous study of ours suggested that upregulation of NR5A1 during early gonadal differentiation in male (46,XY) human pluripotent stem cells steers the cells into a more mature gonadal cell type. However, the detailed role of NR5A1 in female gonadal differentiation has yet to be determined. In this study, by combining the processes of gonadal differentiation and conditional gene activation, we show that NR5A1 induction predominantly upregulates the female gonadal marker inhibin subunit α (INHA) and steroidogenic markers steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 17 subfamily A member 1 (CYP17A1), hydroxy-delta-5-steroid dehydrogenase (HSD3B2) and hydroxysteroid 17-beta dehydrogenase 1 (HSD17B1). In contrast, NR5A1 induction did not seem to affect the bipotential gonadal markers gata binding protein 4 (GATA4) and Wilms tumour suppressor 1 (WT1) nor the female gonadal markers r-spondin 1 (RSPO1) and wnt family member 4 (WNT4). Differentially expressed genes were highly associated with adrenal and ovarian steroidogenesis pathways. Moreover, time-series analysis revealed different dynamic changes between male and female -induced samples, where continuously upregulated genes in female gonadal differentiation were mostly associated with adrenal steroidogenesis. Thus, in contrast to male gonadal differentiation, NR5A1 is necessary but not sufficient to steer human embryonic stem cell (hESC)-derived bipotential gonadal-like cells towards a more mature somatic, female cell fate. Instead, it seems to direct bipotential gonadal-like cells more towards a steroidogenic-like cell population. The information obtained in this study helps in elucidating the role of NR5A1 in gonadal differentiation of a female stem cell line.

Project description:The widely distributed thicklip grey mullet (Chelon labrosus) has been proposed as a suitable sentinel of pollution since it is able to survive heavily polluted marine/estuarine waters. Previous studies applying molecular to histological level biomarkers have indicated that mullets respond to exposure to chemical compounds. Microarrays are used to identify gene pathways responsive to specific chemical exposures. In this context, fragments of 129 genes relevant in peroxisome proliferation, detoxification, lipid metabolism, inflammatory/immune response, metal sequestration, oxidative and general stress, cell cycle regulation and proliferation, apoptosis, protein synthesis/degradation, and endocrine disruption were cloned through homological cloning using degenerate primers for microchip creation. Additional 31 sequences available in databases belonging to mugilid fishes were included in the final Agilent custom-microchip design. Female multitissue transcritome analysis was performed in mullets from Ondarrua. 108 genes showed differential expression when comparing female brain, gonad, gill and liver. Typical brain transcripts such as aromatase or dopamine receptor were expressed preferentially in the brain, whereas liver specific genes were detected in the liver; choriogenin-L, vitellogenins, fibrinogens or hepatocyte growth-factor. Genes related to peroxisome proliferation were systematically overrepresented in gonads. Female thicklip grey mullet tissue transcriptome comparission from Ondarrua, Basque Country GSM861357-GSM861379: 23 samples: 5 female samples from Gonad: female-Ondarru (F-L); 6 female samples from gonad: female-Ondarru (F-GO); 6 female samples from gill: female-Ondarru (F-GI); 6 female samples from brain: female-Ondarru (F-B); GSM886139-GSM886153: 15 samples: 2 intersex samples from Ondarru (I-L); 2 intersex gonad samples: intersex-Ondarru (I-GO); 6 female hepatic samples: female-Arriluze (F-A); 5 male hepatic samples: male-Arriluze (M-A) Immature Thicklip grey mullets were exposed to accetone, cadmium, benzo(a)pyrene and to nonylphenol and hepatic transcriptome was compared GSM886154-GSM886183: 30 samples: immature thicklip grey mullets hepatic samples 6 control seawater exposed samples, 6 acetone exposed samples; 6 cadmium exposed samples, 6 benzo(a)pyrene exposed samples (BAP) and 6 nonylphenol (NP) exposed samples.

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Molecular and cellular design of ovotestis development

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