scholarly journals Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1103
Author(s):  
Furong Tang ◽  
Nainoa Richardson ◽  
Audrey Albina ◽  
Marie-Christine Chaboissier ◽  
Aitana Perea-Gomez
Keyword(s):  
Granulosa Cells ◽  
Gonad Development ◽  
Supporting Cell ◽  
Gonadal Development ◽  
Ovary Development ◽  
Double Knockout ◽  
Cell Identity ◽  
Knockout Mouse Model ◽  
Steroidogenic Cell ◽  
Male Specific

The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when Sox9 and Wnt4 are both mutated. We show that the XX gonad mutant for Wnt4 or for both Wnt4 and Sox9 develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a Wnt4 mutation. Sox9 deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY Sox9 mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of Wnt4 or Rspo1, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY Sox9 Wnt4 double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.

scholarly journals Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis

2021 ◽  
Author(s):  
Shu-Yun Li ◽  
Xiaowei Gu ◽  
Anna Heinrich ◽  
Emily G. Hurley ◽  
Blanche Capel ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Immune Cell ◽  
Gonad Development ◽  
Myeloid Cell ◽  
Cell Types ◽  
Double Knockout ◽  
Fetal Mouse ◽  
Testis Differentiation ◽  
Male Specific ◽  
Testis Cord

AbstractTestis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb;Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.Summary statementDeletion of Mafb and Maf genes leads to supernumerary monocytes in fetal mouse gonads, resulting in vascular, morphogenetic, and differentiation defects during testicular organogenesis.

Inactivation of Wt1 causes pre-granulosa cell to steroidogenic cell transformation and defect of ovary development†

2020 ◽  
Vol 103 (1) ◽  
pp. 60-69
Author(s):  
Changhuo Cen ◽  
Min Chen ◽  
Jingjing Zhou ◽  
Lianjun Zhang ◽  
Shuguang Duo ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Sertoli Cells ◽  
Cell Transformation ◽  
Ovary Development ◽  
Marker Genes ◽  
Cell Marker ◽  
Lineage Specification ◽  
Steroidogenic Cell ◽  
Steroidogenic Cells

Abstract Wt1 gene encodes a nuclear transcription factor which is specifically expressed in ovarian granulosa cells and testicular Sertoli cells. Our previous studies demonstrated that Wt1 is required for the lineage specification of supporting cells and inactivation of Wt1 results in Sertoli cells to Leydig-like cells transformation. To test whether Wt1 is also involved in lineage maintenance of granulosa cells during ovary development, Wt1 was specifically deleted in pre-granulosa cells using Foxl2-cre. We found that the female Wt1−/flox; Foxl2-cre mice were infertile with atrophic ovaries and no growing follicles with multiple layers of granulosa cells were observed. A large number of 3β-HSD-positive steroidogenic cells were detected in ovaries of Wt1−/flox; Foxl2-cre mice during embryonic stage and these cells were derived from Foxl2-expressing pre-granulosa cells. The quantitative results showed the expression of granulosa cell marker genes (Foxl2, Follistatin) was downregulated and steroidogenic cell marker genes (3β-HSD, Cyp11a1, Star and Sf1) was dramatically increased in Wt1−/flox; Foxl2-cre ovaries. We also found that the meiosis of germ cells in Wt1−/flox; Foxl2-cre ovaries was delayed but not arrested. This study demonstrates that Wt1 is required for lineage maintenance of granulosa cells and inactivation of Wt1 results in pre-granulosa cells to steroidogenic cells transformation which in turn causes the defect of ovary development.

scholarly journals A Transient Hermaphroditic Stage in Early Male Gonadal Development in Little Yellow Croaker, Larimichthys polyactis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing-Ping Xie ◽  
Bing-Bing Li ◽  
Wei Zhan ◽  
Feng Liu ◽  
Peng Tan ◽  
...  
Keyword(s):  
Germ Cells ◽  
Evolutionary Relationship ◽  
Gonadal Development ◽  
Ovary Development ◽  
Larimichthys Polyactis ◽  
Efferent Duct ◽  
Sequential Hermaphroditism ◽  
Serum Hormone ◽  
Early Primary ◽  
Male Specific

Animal taxa show remarkable variability in sexual reproduction, where separate sexes, or gonochorism, is thought to have evolved from hermaphroditism for most cases. Hermaphroditism accounts for 5% in animals, and sequential hermaphroditism has been found in teleost. In this study, we characterized a novel form of the transient hermaphroditic stage in little yellow croaker (Larimichthys polyactis) during early gonadal development. The ovary and testis were indistinguishable from 7 to 40 days post-hatching (dph). Morphological and histological examinations revealed an intersex stage of male gonads between 43 and 80 dph, which consist of germ cells, somatic cells, efferent duct, and early primary oocytes (EPOs). These EPOs in testis degenerate completely by 90 dph through apoptosis yet can be rescued by exogenous 17-β-estradiol. Male germ cells enter the mitotic flourishing stage before meiosis is initiated at 180 dph, and they undergo normal spermatogenesis to produce functional sperms. This transient hermaphroditic stage is male-specific, and the ovary development appears to be normal in females. This developmental pattern is not found in the sister species Larimichthys crocea or any other closely related species. Further examinations of serum hormone levels indicate that the absence of 11-ketotestosterone and elevated levels of 17-β-estradiol delineate the male intersex gonad stage, providing mechanistic insights on this unique phenomenon. Our research is the first report on male-specific transient hermaphroditism and will advance the current understanding of fish reproductive biology. This unique gonadal development pattern can serve as a useful model for studying the evolutionary relationship between hermaphroditism and gonochorism, as well as teleost sex determination and differentiation strategies.

scholarly journals Single-cell roadmap of human gonadal development

2021 ◽  
Author(s):  
Roser Vento-Tormo ◽  
Luz Garcia-Alonso ◽  
Valentina Lorenzi ◽  
Cecilia Mazzeo ◽  
Carmen Sancho-Serra ◽  
...  
Keyword(s):  
Single Cell ◽  
Granulosa Cells ◽  
Mammalian Species ◽  
Supporting Cell ◽  
Gonadal Development ◽  
Chromatin Accessibility ◽  
In Vitro Models ◽  
Second Trimester ◽  
Germ Cell Differentiation

Abstract Gonadal development is a complex process that involves sex determination followed by divergent maturation into ovaries or testes. Historically, limited tissue accessibility and lack of reliable in vitro models have impeded our understanding of human gonadogenesis, despite its importance in gonadal pathologies and infertility. Here, we generated a comprehensive map of first- and second-trimester gonadal development using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and imaging. Using this approach, we identified novel transcription factors and cell states in human germ and supporting cell lineages. We compared them with other mammalian species and found primate-specific regulatory programmes. Our data identified cell context–specific interactions shaping sex specification and development of human germ cells. We defined a novel bipotent progenitor cell (LGR5+, TSPAN8+) in late embryos that can differentiate into early Sertoli in males or pre-granulosa cells in females. In fetal ovaries, we defined two subsets of pre-granulosa cells supporting germ-cell differentiation and distributed across the cortico-medullary axis. We also found a subset of developing granulosa cells appearing during the second trimester of pregnancy that is involved in follicular assembly. In fetal testes, we defined a novel supporting population (sPAX8 cells) located at the poles of the developing testis cords. We also found two tissue-resident myeloid populations that we named microglia-like and SIGLEC15+ fetal testicular macrophages. This study provides an unprecedented spatiotemporal map of human gonadal differentiation that can be utilised as a blueprint for in vitro gametogenesis.

scholarly journals Expression of Wsb2 in the developing and adult mouse testis

Reproduction ◽  
2007 ◽  
Vol 133 (4) ◽  
pp. 753-761 ◽  
Author(s):  
M A Sarraj ◽  
P J McClive ◽  
A Szczepny ◽  
H Daggag ◽  
K L Loveland ◽  
...  
Keyword(s):  
Real Time ◽  
Germ Cells ◽  
Adult Mouse ◽  
Gonad Development ◽  
Gonadal Development ◽  
Mouse Testis ◽  
Hedgehog Signalling ◽  
Real Time Analysis ◽  
Female Specific ◽  
Male Specific

We present a detailed study of the expression pattern of WD repeat and SOCS box-containing 2 (Wsb2) in mouse embryonic and adult gonads. Wsb2 was previously identified in a differential screen aimed at identifying the genes involved in male- and female-specific gonadal development. Wsb2 expression was analysed during mouse gonadogenesis by real-time PCR, whole-mount and section in situ hybridisation and immunofluorescence. Wsb2 mRNA expression was initially detected in gonads of both sexes from 11.5 days post coitum (dpc) until 12.0 dpc. By 12.5 dpc and thereafter, Wsb2 expression rapidly decreased in the female, while persisting in the male gonads. In foetal, newborn and juvenile testes, Wsb2 mRNA and protein were readily detected in the seminiferous cords within both Sertoli and germ cells. Wsb2 mRNA was present in spermatogonia, spermatocytes and in Sertoli cells of the adult mouse testis. The differential expression of Wsb2 in male versus female embryonic gonads suggests some male-specific role in gonad development, and its expression in the first wave of spermatogenesis indicates a role in germ cells. Real-time analysis of adult mouse testis tubules cultured in the presence of the Hedgehog signalling inhibitor, cyclopamine, showed a downregulation of Wsb2 mRNA after treatment which suggests that Wsb2 may be a target of Hedgehog signalling.

scholarly journals OVARY DEVELOPMENT, FSH AND LH GENES EXPRESSION OF INDONESIAN LEAFFISH, Pristolepis grootii (Bleeker, 1852), INJECTED WITH LUTEINIZING HORMONE-RELEASING HORMONE ANALOG

2021 ◽  
Vol 16 (2) ◽  
pp. 69
Author(s):  
Muslim Muslim ◽  
Agus Oman Sudrajat ◽  
Muhammad Zairin Jr. ◽  
Muhammad Agus Suprayudi ◽  
Arief Boediono ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Gonadosomatic Index ◽  
Gonad Development ◽  
Gonadal Development ◽  
Ovary Development ◽  
Optimum Dose ◽  
Female Gonad ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hormone Analog

Indonesian leaffish, Pristolepis grootii (Bleeker, 1852), is an undomesticated freshwater fish species native to the rivers, flooded swamps, and tributaries of Indonesia. The fish is mainly captured for consumption. In order to prevent its extinction and supply its growing demands, the artificial breeding of the fish should be developed. The purpose of this study was to determine the optimum dose of luteinizing hormone-releasing hormone analog (LHRHa) for stimulating the female P. grootii gonadal development at a dosage of 0, 1, 10, and 50 µg kg-1 of fish. Female fish (20.0 ± 0.6 g) were adapted for 30 days in the rearing environment and then separated into 12 aquariums with six fish per aquarium. Fish were then reared for another 21 days and fed with Tubifex sp. The LHRHa injection was conducted twice on day-7 and 14. Fish bodyweight, gonadosomatic index, gonad histology, blood estradiol-17â, and FSH-â and LH-â gene expression were evaluated at day 0, 7, 14, and 21. The results showed that the injection of the LHRHa hormone stimulated the development of fish gonads and was better achieved with a higher concentration of LHRHa. The best treatment was observed by the administration of 50 µg kg-1 of LHRHa that produced the fastest development among all treatments. This study demonstrated that the LHRHa induction could potentially stimulate the gonadal development of the newly domesticated fish. To our knowledge, this is the first study that reported the success of the induction of female gonad development in the Indonesian leaffish P. grooti.KEYWORDS: 

scholarly journals IRX3 and IRX5 collaborate during ovary development and follicle formation to establish responsive granulosa cells in the adult mouse†

2020 ◽  
Vol 103 (3) ◽  
pp. 620-629
Author(s):  
Anqi Fu ◽  
Megan L Koth ◽  
Ryan M Brown ◽  
Sarah A Shaw ◽  
Linda Wang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Primordial Follicle ◽  
Oocyte Quality ◽  
Ovary Development ◽  
Double Knockout ◽  
Specific Expression ◽  
Two Factors ◽  
And Function

Abstract Healthy development of ovarian follicles depends on appropriate interactions and function between oocytes and their surrounding granulosa cells. Previously, we showed that double knockout of Irx3 and Irx5 (Irx3/5 DKO) in mice resulted in abnormal follicle morphology and follicle death. Further, female mouse models of individual Irx3 or Irx5 knockouts were both subfertile but with distinct defects. Notably, the expression profile of each gene suggests independent roles for each; first, they are colocalized in pre-granulosa cells during development that then progresses to include oocyte expression during germline nest breakdown and primordial follicle formation. Thereafter, their expression patterns diverge between oocytes and granulosa cells coinciding with the formulation and maturation of intimate oocyte–granulosa cell interactions. The objective of this study was to investigate the contributions of Irx5 and somatic cell-specific expression of Irx3 during ovarian development. Our results show that Irx3 and Irx5 contribute to female fertility through different mechanisms and that Irx3 expression in somatic cells is important for oocyte quality and survival. Based on evaluation of a series of genetically modified mouse models, we conclude that IRX3 and IRX5 collaborate in the same cells and then in neighboring cells to foster a healthy and responsive follicle. Long after these two factors have extinguished, their legacy enables these intercellular connections to mature and respond to extracellular signals to promote follicle maturation and ovulation.

scholarly journals Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†

2021 ◽  
Author(s):  
Shu-Yun Li ◽  
Xiaowei Gu ◽  
Anna Heinrich ◽  
Emily G Hurley ◽  
Blanche Capel ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Immune Cell ◽  
Gonad Development ◽  
Myeloid Cell ◽  
Cell Types ◽  
Double Knockout ◽  
Testis Differentiation ◽  
Male Specific ◽  
Testis Cord

Abstract Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.

Comparative Transcriptomic Analysis of Gonad Development and Renewal of Ovoviviparous Black Rockfish (Sebastes Schlegelii)

2020 ◽  
Author(s):  
Jianshaung Li ◽  
Haishen Wen ◽  
Likang Lyu ◽  
Yun Li ◽  
Xiaojie Wang ◽  
...  
Keyword(s):  
Gonad Development ◽  
Gonadal Development ◽  
Ovary Development ◽  
Reproductive Pattern ◽  
Cell Renewal ◽  
Rna Seq ◽  
Intercellular Interaction ◽  
Black Rockfish ◽  
Kegg Pathways ◽  
Sebastes Schlegelii

Abstract Background: Black rockfish (Sebastes schlegelii) has an ovoviviparous reproductive pattern and long-term sperm storage, which resulting in asynchronous gonadal development between the sexes. While the comprehensive understanding of gonad development of black rockfish has not been well studied. Here, we study the gonad development and germ cell renewal by histology and RNA-seq.Results: In this study, RNA-seq was performed on both testis and ovary to characterize key pathways and genes during development and gamete maturation in black rockfish. Different expression genes (DEGs) were identified and annotated in 4 comparisons (F_III vs F_IV, F_IV vs F_V, M_III vs M_IV and M_IV vs M_V). Based on enriched analysis of DEGs in testis, 11 and 14 significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mapped in M_III vs M_IV group and M_IV vs M_V group, respectively. And DEGs in ovary development periods were also classified into 10 biological function group. The results of the q-PCR expression pattern of the selected genes was significantly correlated with the RNA-Seq results, implying the reliability and accuracy of the RNA-Seq analysis.Conclusion: The categories intercellular interaction and cytoskeleton, molecule amplification and repairment in cell cycle were revealed to be crucial in testis development and spermatogenesis along with a series of metabolite biosynthesis. Our results provided a comprehensive insight into the black rockfish gonad development for further study of reproductive physiology and molecular biology in ovoviviparity.

IMPLANTATION OF LHRH-a HORMONE TO STIMULATION OF GONAD DEVELOPMENT OF HUMPBACK GROUPER SECOND GENERATION ( F-2 )

2013 ◽  
Vol 5 (2) ◽  
Author(s):  
Tridjoko Tridjoko
Keyword(s):  
Body Weight ◽  
Second Generation ◽  
Gonad Development ◽  
Gonadal Development ◽  
Oocyte Diameter ◽  
2Nd Generation ◽  
Length Range ◽  
Concrete Tank ◽  
Implant Treatment ◽  
Stimulation Of

This study aimed to determine the effect of LHRH-a hormone implantation on gonadal development of humpback grouper, Cromileptes altivelis 2nd generation (F-2). Individuals used were 20 female grouper fish with weight range of 600-800 gram/fish and total length range of 28.0-30.0 cm. The treatment used 5 fish each with tagging. Grouper fishes were stocked into the 75 m3 circular concrete tank. Hormone of LHRH-a with dosage of 50 μg/kg body weight was used as implant treatment of (A) 1 time,, (B) 2 times, (C) 3 times, and (D) without implant. The results showed that implantation of LHRH-a hormone were significantly stimulate gonad development of humpback grouper second generation (F-2). Treatment of 3 times implant every month showed the best results produced  oocyte diameter up to 480 μm, while the control of oocyte diameter only reached <400 μm. Keywords: LHRH-a hormone, implantation, Humpback grouper, gonad development

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