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.

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 Metabolism and Sex Differentiation in Animals from a Starvation Perspective

2021 ◽  
pp. 1-11
Author(s):  
Yuta Sakae ◽  
Minoru Tanaka
Keyword(s):  
Sex Determination ◽  
Environmental Changes ◽  
Sex Differentiation ◽  
Green Light ◽  
Acid Synthesis ◽  
Sex Reversal ◽  
Environmental Sex Determination ◽  
Biological Factors ◽  
Signal Transducers ◽  
Male Sex

Animals determine their sex genetically (GSD: genetic sex determination) and/or environmentally (ESD: environmental sex determination). Medaka (<i>Oryzias latipes</i>) employ a XX/XY GSD system, however, they display female-to-male sex reversal in response to various environmental changes such as temperature, hypoxia, and green light. Interestingly, we found that 5 days of starvation during sex differentiation caused female-to-male sex reversal. In this situation, the metabolism of pantothenate and fatty acid synthesis plays an important role in sex reversal. Metabolism is associated with other biological factors such as germ cells, HPG axis, lipids, and epigenetics, and supplys substances and acts as signal transducers. In this review, we discuss the importance of metabolism during sex differentiation and how metabolism contributes to sex differentiation.

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.

scholarly journals Transcriptional Regulation of the Y-Linked Mammalian Testis-Determining Gene SRY

2021 ◽  
pp. 1-9
Author(s):  
Naoki Okashita ◽  
Makoto Tachibana
Keyword(s):  
Sex Determination ◽  
Sex Differentiation ◽  
Disorders Of Sex Development ◽  
Sex Reversal ◽  
Cis Acting ◽  
Male Development ◽  
Sex Development ◽  
Epigenetic Modifier ◽  
Male Sex ◽  
Testis Determining Gene

Mammalian male sex differentiation is triggered during embryogenesis by the activation of the Y-linked testis-determining gene <i>SRY</i>. Since insufficient or delayed expression of <i>SRY</i> results in XY gonadal sex reversal, accurate regulation of <i>SRY</i> is critical for male development in XY animals. In humans, dysregulation of <i>SRY</i> may cause disorders of sex development. Mouse <i>Sry</i> is the most intensively studied mammalian model of sex determination. <i>Sry</i> expression is controlled in a spatially and temporally stringent manner. Several transcription factors play a key role in sex determination as trans-acting factors for <i>Sry</i> expression. In addition, recent studies have shown that several epigenetic modifications of <i>Sry</i> are involved in sex determination as cis-acting factors for <i>Sry</i> expression. Herein, we review the current understanding of transcription factor- and epigenetic modifier-mediated regulation of <i>SRY</i>/<i>Sry</i> expression.

Role of mammalian Y chromosome in sex determination

1988 ◽  
Vol 322 (1208) ◽  
pp. 63-72 ◽  
Keyword(s):  
Cell Differentiation ◽  
Sex Determination ◽  
Y Chromosome ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Sex Reversal ◽  
Testicular Development ◽  
Chimeric Mouse ◽  
Embryonic Gonad

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.

scholarly journals Green light irradiation during sex differentiation induces female-to-male sex reversal in the medaka Oryzias latipes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Oki Hayasaka ◽  
Yutaka Takeuchi ◽  
Kazuhiro Shiozaki ◽  
Kazuhiko Anraku ◽  
Tomonari Kotani
Keyword(s):  
Sex Differentiation ◽  
Green Light ◽  
Oryzias Latipes ◽  
Sex Reversal ◽  
Light Irradiation ◽  
Male Sex

scholarly journals The mir-35 family links maternal germline sex to embryonic viability in C. elegans

2019 ◽  
Author(s):  
Lars Benner ◽  
Katherine Prothro ◽  
Katherine McJunkin
Keyword(s):  
Sex Determination ◽  
Germ Cells ◽  
Sex Reversal ◽  
Loss Of Function ◽  
Wild Type ◽  
Partial Loss ◽  
C Elegans ◽  
Germline Sex Determination ◽  
Embryonic Viability ◽  
Male Gene

AbstractThe germline sex determination pathway in C. elegans determines whether germ cells develop as oocytes or sperm, with no previously known effect on viability. The mir-35 family of microRNAs are expressed in the C. elegans germline and embryo and are essential for both viability and normal hermaphroditic sex determination, preventing aberrant male gene expression in XX hermaphrodite embryos. Here we show that combining feminizing mutations with partial loss of function of the mir-35 family results in enhanced penetrance embryonic lethality that preferentially kills XO animals. This lethal phenotype is due to altered signaling through the germline sex determination pathway, and maternal germline feminization is sufficient to induce enhanced lethality. These findings reveal a surprising pleiotropy of sperm-fate promoting pathways on organismal viability. Overall, our results demonstrate an unexpectedly strong link between sex determination and embryonic viability, and suggest that in wild type animals, mir-35 family members buffer against misregulation of pathways outside the sex determination program, allowing for clean sex reversal rather than deleterious effects of perturbing sex determination genes.

scholarly journals DNA Methylation Reprogramming during Sex Determination and Transition in Zebrafish

2020 ◽  
Author(s):  
Xinxin Wang ◽  
Xin Ma ◽  
Gaobo Wei ◽  
Weirui Ma ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Sex Determination ◽  
Sexual Development ◽  
Epigenetic Modification ◽  
Sex Differentiation ◽  
Primordial Germ Cells ◽  
Regulation Of Gene Expression ◽  
Adult Zebrafish ◽  
Germline Development ◽  
Male Sex

AbstractIt is a mystery about sex determination and sexual plasticity in species without sex chromosomes. DNA methylation is a prevalent epigenetic modification in vertebrates, which has been shown to involve in the regulation of gene expression and embryo development. However, it remains unclear about how DNA methylation regulates sexual development. To elucidate it, we used zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We revealed that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germline development and set to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When blocking DNMTs activity in juveniles after 9 dpf, the zebrafish preferably develops into females. We also show that Tet3 involves in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMTs activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germline development and sexual plasticity.

Igf3 is essential for ovary differentiation in zebrafish†

2020 ◽  
Author(s):  
Yuxin Xie ◽  
Duo Huang ◽  
Lianhe Chu ◽  
Yun Liu ◽  
Xiao Sun ◽  
...  
Keyword(s):  
Sexual Differentiation ◽  
Gene Knockout ◽  
Sex Differentiation ◽  
Sex Reversal ◽  
Estrogen Signaling ◽  
Differential Expression Pattern ◽  
Male Sex ◽  
In Vitro Treatment

Abstract Zebrafish gonadal sexual differentiation is an important but poorly understood subject. Previously, we have identified a novel Igf named Igf3 in teleosts. The importance of Igf3 in oocyte maturation and ovulation has been recently demonstrated by us in zebrafish. In this study, we have further found the essential role of Igf3 in gonadal sexual differentiation of zebrafish. A differential expression pattern of igf3 between ovary and testis during sex differentiation (higher level in ovary than in testis) was found in zebrafish. An igf3 knockout zebrafish line was established using TALENs-mediated gene knockout technique. Intriguingly, all igf3 homozygous mutants were males due to the female-to-male sex reversal occurred during sex differentiation. Further analysis showed that Igf3 did not seem to affect the formation of so-called juvenile ovary and oocyte-like germ cells. Oocyte development was arrested at primary growth stage, and the ovary was gradually sex-reversed to testis before 60 dpf. Such sex reversal was likely due to decreased germ cell proliferation by suppressing PI3K/Akt pathway in early ovaries of igf3 mutants. Estrogen is considered as a master regulator in fish sex differentiation. Here, we found that igf3 expression could be up-regulated by estrogen in early stages of ovarian follicles as evidenced in in vitro treatment assays and cyp19a1a mutant zebrafish, and E2 failed to rescue the defects of igf3 mutants in ovarian development, suggesting that Igf3 may serve as a downstream factor of estrogen signaling in sex differentiation. Taken together, we demonstrated that Igf3 is essential for ovary differentiation in zebrafish.

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