scholarly journals Müllerian-inhibiting substance (MIS) is both necessary and sufficient for testicular differentiation in Chinese soft-shelled turtle Pelodiscus sinensis

2019 ◽  
Author(s):  
Yingjie Zhou ◽  
Wei Sun ◽  
Han Cai ◽  
Haisheng Bao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Sex Reversal ◽  
Testicular Development ◽  
Loss Of Function ◽  
Pelodiscus Sinensis ◽  
Specific Expression ◽  
Müllerian Inhibiting Substance ◽  
Male Sex ◽  
Necessary And Sufficient ◽  
Reptilian Species ◽  
Mullerian Inhibiting Substance

ABSTRACTMüllerian-inhibiting substance (Mis, or anti-müllerian hormone, Amh), a member of TGF-β superfamily, as initiator or key regulator in sexual development has been well documented in some vertebrates, especially in fish. However, its functional role has not been identified yet in reptiles. Here we characterized the Mis gene in Chinese soft-shelled turtle Pelodiscus sinensis (P. sinensis), a typical reptilian species exhibiting ZZ/ZW sex chromosomes. The mRNA of Mis was initially expressed in male embryonic gonads by stage 15, preceding gonadal sex differentiation, and exhibited male-specific expression pattern throughout embryogenesis. Moreover, Mis was rapidly up-regulated during female-to-male sex reversal induced by aromatase inhibitor letrozole. Most importantly, Mis loss of function by RNA interference led to complete feminization of genetic male (ZZ) gonads, suppression of the testicular marker Sox9, and upregulation of the ovarian regulator Cyp19a1. Conversely, overexpression of Mis in ZW embryos resulted in female-to-male sex reversal, characterized by the formation of testis structure, ectopic activation of Sox9, and a remarkable decline in Cyp19a1. Collectively, these findings provide the first solid evidence that Mis is both necessary and sufficient to drive testicular development in a reptilian species, P. sinensis, highlighting the significance of the TGF-β pathway in reptilian sex determination.

scholarly journals The Role of Anti-Müllerian Hormone in Testis Differentiation Reveals the Significance of the TGF-β Pathway in Reptilian Sex Determination

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1317-1327 ◽  
Author(s):  
Yingjie Zhou ◽  
Wei Sun ◽  
Han Cai ◽  
Haisheng Bao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Sex Determination ◽  
Messenger Rna ◽  
Sex Differentiation ◽  
Sex Reversal ◽  
Testicular Development ◽  
Loss Of Function ◽  
Specific Expression ◽  
Male Sex ◽  
Specific Expression Pattern ◽  
Reptilian Species

Anti-Müllerian hormone (Amh, or Müllerian-inhibiting substance, Mis), a member of TGF-β superfamily, has been well documented in some vertebrates as initiator or key regulator in sexual development, and particularly in fish. However, its functional role has not yet been identified in reptiles. Here, we characterized the Amh gene in the Chinese soft-shelled turtle Pelodiscus sinensis, a typical reptilian species exhibiting ZZ/ZW sex chromosomes. The messenger RNA of Amh was initially expressed in male embryonic gonads by stage 15, preceding gonadal sex differentiation, and exhibited a male-specific expression pattern throughout embryogenesis. Moreover, Amh was rapidly upregulated during female-to-male sex reversal induced by aromatase inhibitor letrozole. Most importantly, Amh loss of function by RNA interference led to complete feminization of genetic male (ZZ) gonads, suppression of the testicular marker Sox9, and upregulation of the ovarian regulator Cyp19a1. Conversely, overexpression of Amh in ZW embryos resulted in female-to-male sex reversal, characterized by the formation of a testis structure, ectopic activation of Sox9, and a remarkable decline in Cyp19a1. Collectively, these findings provide the first solid evidence that Amh is both necessary and sufficient to drive testicular development in a reptilian species, P. sinensis, highlighting the significance of the TGF-β pathway in reptilian sex determination.

Ovarian aromatase loss-of-function mutant medaka undergo ovary degeneration and partial female-to-male sex reversal after puberty

2018 ◽  
Vol 460 ◽  
pp. 104-122 ◽  
Author(s):  
Masatoshi Nakamoto ◽  
Yasushi Shibata ◽  
Kaoru Ohno ◽  
Takeshi Usami ◽  
Yasuhiro Kamei ◽  
...  
Keyword(s):  
Sex Reversal ◽  
Loss Of Function ◽  
Male Sex

scholarly journals FGF9 is a downstream target of SRY and sufficient to determine male sex fate in ex vivo XX gonad culture

2020 ◽  
Vol 103 (6) ◽  
pp. 1300-1313
Author(s):  
Yi-Han Li ◽  
Tsung-Ming Chen ◽  
Bu-Miin Huang ◽  
Shang-Hsun Yang ◽  
Chia-Ching Wu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Fate ◽  
Ex Vivo ◽  
Disorders Of Sex Development ◽  
Sex Reversal ◽  
Vital Role ◽  
Loss Of Function ◽  
Downstream Target ◽  
Sex Development ◽  
Male Sex

Abstract Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays critical roles in embryonic and organ developments and is involved in diverse physiological events. Loss of function of FGF9 exhibits male-to-female sex reversal in the transgenic mouse model and gain of FGF9 copy number was found in human 46, XX sex reversal patient with disorders of sex development. These results suggested that FGF9 plays a vital role in male sex development. Nevertheless, how FGF9/Fgf9 expression is regulated during testis determination remains unclear. In this study, we demonstrated that human and mouse SRY bind to −833 to −821 of human FGF9 and −1010 to −998 of mouse Fgf9, respectively, and control FGF9/Fgf9 mRNA expression. Interestingly, we showed that mouse SRY cooperates with SF1 to regulate Fgf9 expression, whereas human SRY-mediated FGF9 expression is SF1 independent. Furthermore, using an ex vivo gonadal culture system, we showed that FGF9 expression is sufficient to switch cell fate from female to male sex development in 12–16 tail somite XX mouse gonads. Taken together, our findings provide evidence to support the SRY-dependent, fate-determining role of FGF9 in male sex development.

scholarly journals Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of R-spondin1 in mouse sex reversals

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nainoa Richardson ◽  
Isabelle Gillot ◽  
Elodie P Gregoire ◽  
Sameh A Youssef ◽  
Dirk de Rooij ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Sertoli Cell ◽  
Sex Reversal ◽  
Loss Of Function ◽  
Triple Mutant ◽  
Genetic Ablation ◽  
Ovarian Differentiation ◽  
Testicular Differentiation ◽  
Male Sex

In mammals, testicular differentiation is initiated by transcription factors SRY and SOX9 in XY gonads, and ovarian differentiation involves R-spondin1 (RSPO1) mediated activation of WNT/β-catenin signaling in XX gonads. Accordingly, the absence of RSPO1/Rspo1 in XX humans and mice leads to testicular differentiation and female-to-male sex reversal in a manner that does not requireSry or Sox9 in mice. Here we show that an alternate testis-differentiating factor exists and that this factor is Sox8. Specifically, genetic ablation of Sox8 and Sox9 prevents ovarian-to-testicular reprogramming observed in XX Rspo1 loss-of-function mice. Consequently, Rspo1 Sox8 Sox9 triple mutant gonads developed as atrophied ovaries. Thus, SOX8 alone can compensate for the loss of SOX9 for Sertoli cell differentiation during female-to-male sex reversal.

scholarly journals Sox8 and Sox9 act redundantly for ovarian-to-testicular fate reprogramming in the absence of R-spondin1 in mouse sex reversals

2019 ◽  
Author(s):  
Nainoa Richardson ◽  
Isabelle Gillot ◽  
Elodie P. Gregoire ◽  
Sameh A. Youssef ◽  
Dirk G. de Rooij ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Sertoli Cell ◽  
Sex Reversal ◽  
Loss Of Function ◽  
Triple Mutant ◽  
Genetic Ablation ◽  
Ovarian Differentiation ◽  
Testicular Differentiation ◽  
Male Sex

AbstractIn mammals, testicular differentiation is initiated by transcription factors SRY and SOX9 in XY gonads, and ovarian differentiation involves R-spondin1 (RSPO1) mediated activation of WNT/β-catenin signaling in XX gonads. Accordingly, the absence of RSPO1/Rspo1 in XX humans and mice leads to testicular differentiation and female-to-male sex reversal in a manner that does not require Sry or Sox9 in mice. Here we show that an alternate testis-differentiating factor exists and that this factor is Sox8. Specifically, genetic ablation of Sox8 and Sox9 prevents ovarian-to-testicular reprogramming observed in XX Rspo1 loss-of-function mice. Consequently, Rspo1 Sox8 Sox9 triple mutant gonads developed as atrophied ovaries. Thus, SOX8 alone can compensate for the loss of SOX9 for Sertoli cell differentiation during female-to-male sex reversal.

Sex differentiation in bilaterally allophenic animals produced by cloning of two bipartite male/female chimaeras of Lineus sanguineus

Development ◽  
1981 ◽  
Vol 65 (1) ◽  
pp. 173-184
Author(s):  
S. Sivaradjam ◽  
J. Bierne
Keyword(s):  
Ovarian Development ◽  
Sex Differentiation ◽  
Sex Reversal ◽  
Testicular Development ◽  
Gonadal Differentiation ◽  
Male And Female ◽  
Diffusible Factor ◽  
Male Sex ◽  
The Many ◽  
The Right

Two bipartite chimaeras were constructed in Lineus sanguineus by grafting the lateral halves from a phenotypically dark-brown male onto the anatomically complementary halves from a phenotypically light-brown female. Regeneration of a large number of pieces transected from these two bilaterally allogeneic chimaeras produced two clones of bilaterally allophenic nemertines (♂/♀ and ♀/♂) Sex differentiation in the cloned worms started with a transitory stage of gonad developmental autonomy, termed the primary gynandromorphous state; at this stage there were young testes in the originally male lateral halves and juvenile ovaries in the originally female ones, the only abnormality then was that the ovarian development was more advanced than the testicular development relative to those in male and female controls. Then, unilateral sex reversal occurred, with feminization of the testes, i.e. oogenesis took the place of spermatogenesis in the many male gonads located in either the right or the left side of allophenic worms according to the symmetry patterns of the two clones. Finally, when the gonads reached maturity, both sides of allophenic L. sanguineus contained only ovaries with ripe oocytes. The complete feminization of these allophenic worms and the previously observed masculinization of ‘heterosexual’ chimaeras in L. ruber suggest that a diffusible factor controls gonadal differentiation in worms of the prevailing sex, which is the female sex in L. sanguineus and the male sex in L. ruber.

Gubernacular development in Müllerian inhibiting substance receptor-deficient mice

2002 ◽  
Vol 89 (1) ◽  
pp. 113-118 ◽  
Author(s):  
J.E. Bartlett ◽  
S.M.Y. Lee ◽  
Y. Mishina ◽  
R.R. Behringer ◽  
N. Yang ◽  
...  
Keyword(s):  
Müllerian Inhibiting Substance ◽  
Deficient Mice ◽  
Mullerian Inhibiting Substance

scholarly journals Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells

2007 ◽  
Vol 16 (23) ◽  
pp. 2795-2804 ◽  
Author(s):  
Chris Ottolenghi ◽  
Emanuele Pelosi ◽  
Joseph Tran ◽  
Maria Colombino ◽  
Eric Douglass ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sex Reversal ◽  
Male Sex

scholarly journals Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yildiz Koca ◽  
Benjamin E. Housden ◽  
William J. Gault ◽  
Sarah J. Bray ◽  
Marek Mlodzik
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Planar Cell Polarity ◽  
Egf Receptor ◽  
Control Cell ◽  
Loss Of Function ◽  
Egfr Signaling ◽  
Specific Expression ◽  
Egfr Signaling Pathway ◽  
Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

Ferriman-Gallwey Scores, Serum Androgen and Mullerian Inhibiting Substance Levels in Hirstute Adolescent Girls

2012 ◽  
Vol 25 (5) ◽  
pp. 300-304 ◽  
Author(s):  
S.P. Hertweck ◽  
J.L. Yoost ◽  
M.E. McClure ◽  
Y. Siow ◽  
G.N. Brock ◽  
...  
Keyword(s):  
Adolescent Girls ◽  
Müllerian Inhibiting Substance ◽  
Mullerian Inhibiting Substance
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