Diverse Regulation but Conserved Function: SOX9 in Vertebrate Sex Determination

Vining, Brittany; Ming, Zhenhua; Bagheri‐Fam, Stefan; Harley, Vincent R.

doi:10.3390/genes12040486

Cited by 39 publications

(31 citation statements)

References 190 publications

(99 reference statements)

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“…The molecular mechanisms underlying sex determination and early gonad differentiation have been extensively reviewed and updated in recent years [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Here, we will highlight only the most relevant events, focusing on genes whose function in the adult gonads will be discussed hereafter.…”

Section: Testis and Ovary Cell Lineages Originate From The Same Precursorsmentioning

confidence: 99%

“…Sex determination involves not only the activation of genes necessary for the differentiation of a sexual fate, but also the active repression of the genetic program of the opposite sex [ 16 , 17 , 18 , 19 , 20 , 22 , 23 ]. Some of these molecular interactions operate throughout life, and are summarized in Figure 2 .…”

Section: Antagonism Between Male and Female Factors In Sexual Cell Fate Maintenancementioning

confidence: 99%

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Sex Maintenance in Mammals

Jiménez

Burgos

Barrionuevo

2021

Genes

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The crucial event in mammalian sexual differentiation occurs at the embryonic stage of sex determination, when the bipotential gonads differentiate as either testes or ovaries, according to the sex chromosome constitution of the embryo, XY or XX, respectively. Once differentiated, testes produce sexual hormones that induce the subsequent differentiation of the male reproductive tract. On the other hand, the lack of masculinizing hormones in XX embryos permits the formation of the female reproductive tract. It was long assumed that once the gonad is differentiated, this developmental decision is irreversible. However, several findings in the last decade have shown that this is not the case and that a continuous sex maintenance is needed. Deletion of Foxl2 in the adult ovary lead to ovary-to-testis transdifferentiation and deletion of either Dmrt1 or Sox9/Sox8 in the adult testis induces the opposite process. In both cases, mutant gonads were genetically reprogrammed, showing that both the male program in ovaries and the female program in testes must be actively repressed throughout the individual’s life. In addition to these transcription factors, other genes and molecular pathways have also been shown to be involved in this antagonism. The aim of this review is to provide an overview of the genetic basis of sex maintenance once the gonad is already differentiated.

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Section: Testis and Ovary Cell Lineages Originate From The Same Precursorsmentioning

confidence: 99%

Section: Antagonism Between Male and Female Factors In Sexual Cell Fate Maintenancementioning

confidence: 99%

Sex Maintenance in Mammals

Jiménez

Burgos

Barrionuevo

2021

Genes

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“…Thus, compromised Nr5a1 expression would have played a certain role in the development of reduced testosterone production, as well as decreased Insl3 expression. While expression of Sox9 and Amh was not significantly reduced, despite their expression being upregulated by Nr5a1 [ 30 ], this may be due to Sox9 and Amh expression being controlled by multiple genes, in cooperation with Nr5a1 [ 34 , 35 ]. It is inferred that these factors would have exerted a synergic effect, resulting in the hypofunction of steroidogenic cells.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine Hyponutrition Reduces Fetal Testosterone Production and Postnatal Sperm Count in the Mouse

Fujisawa

Ono

Konno

et al. 2022

Journal of the Endocrine Society

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Although intrauterine hyponutrition is regarded as a risk factor for the development of "testicular dysgenesis syndrome" (TDS) in the human, underlying mechanism(s) remain largely unknown. To clarify the underlying mechanism(s), we fed vaginal plug-positive C57BL/6N female mice with regular food ad libitum throughout the pregnant course (control females) (C-females) or with 50% of the mean daily intake of the C-females from 6.5 dpc (calorie-restricted females) (R-females), and compared male reproductive findings between 17.5-dpc-old male mice delivered from C-females (C-fetuses) and those delivered from R-females (R-fetuses) and between 6-week-old male mice born to C-females (C-offspring) and those born to R-females (R-offspring). Compared with the C-fetuses, the R-fetuses had (1) morphologically normal external genitalia with significantly reduced anogenital distance index, (2) normal numbers of testicular component cells, and (3) significantly low intratesticular testosterone, in association with significantly reduced expressions of steroidogenic genes. Furthermore, compared with the C-offspring, the R-offspring had (1) significantly increased TUNEL-positive cells and normal numbers of other testicular component cells, (2) normal intratesticular testosterone, in association with normal expressions of steroidogenic genes, (3) significantly reduced sperm count, and normal testis weight and sperm motility, and (4) significantly altered expressions of oxidation stress-related, apoptosis-related, and spermatogenesis-related genes. The results, together with the previous data including the association between testosterone deprivation and oxidative stress-evoked apoptotic activation, imply that reduced fetal testosterone production is the primary underlying factor for the development of TDS in intrauterine hyponutrition, and that TDS is included in the clinical spectrum of Developmental Origins of Health and Disease.

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“…Several key lncRNAs have been shown to be involved in male germ cell differentiation, including XLOC_240662, XLOC_362463, and ALDBGALG0000002986 [86]. XLOC_240662 may modulate the progression from embryonic stem cells (ESCs) to SSCs by Sox9, which regulates the meiosis and differentiation of spermatogonia via the Wnt signal pathway [122,123]. XLOC_362463 can modulate the formation of SSCs via the TGFβ/BMP signal pathway.…”

Section: Lncrnas In Livestockmentioning

confidence: 99%

Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

Zhao

Heng

Sahlu

et al. 2021

IJMS

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Long noncoding RNAs (lncRNAs) are composed of nucleotides located in the nucleus and cytoplasm; these are transcribed by RNA polymerase II and are greater than 200 nt in length. LncRNAs fulfill important functions in a variety of biological processes, including genome imprinting, cell differentiation, apoptosis, stem cell pluripotency, X chromosome inactivation and nuclear transport. As high throughput sequencing technology develops, a substantial number of lncRNAs have been found to be related to a variety of biological processes, such as development of the testes, maintaining the self-renewal and differentiation of spermatogonial stem cells, and regulating spermatocyte meiosis. These indicate that lncRNAs can be used as biomarkers and potential therapeutic targets for male infertility. However, only a few comprehensive reviews have described the role of lncRNAs in male reproduction. In this paper, we summarize recent findings relating to the role of lncRNAs in spermatogenesis, their potential as biomarkers for male infertility and the relationship between reproductive arrest and transgenerational effects. Finally, we suggest specific targets for the treatment of male infertility from the perspective of lncRNAs.

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Diverse Regulation but Conserved Function: SOX9 in Vertebrate Sex Determination

Cited by 39 publications

References 190 publications

Sex Maintenance in Mammals

Sex Maintenance in Mammals

Intrauterine Hyponutrition Reduces Fetal Testosterone Production and Postnatal Sperm Count in the Mouse

Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

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