Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis

de Mattos, Karine; Pierre, Kenley Joule; Tremblay, Jacques J.

doi:10.3390/endocrines4030041

Cited by 7 publications

(4 citation statements)

References 211 publications

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“…Strikingly, the steroidogenesis pathway, including genes such as Igf1r, Star, Cyp11a1 and Cyp17a1, was downregulated in Leydig cells of Eif2s3y, Uty and AZFa deletants. Since the production of steroid hormones like testosterone is crucial for germ cell homeostasis 40 , this finding further emphasise the potential contribution of somatic cell deregulation to germ cell phenotypes (Fig. 5g, Extended data Fig.…”

Section: The Impact Of Y Genes On the Testis Transcriptomementioning

confidence: 70%

Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Subrini,

Varsally,

Balaguer Balsells

et al. 2024

Preprint

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The mammalian Y chromosome is essential for male fertility, but how individual Y genes regulate spermatogenesis is poorly understood. To resolve this question, we generate a deletion series of the mouse Y chromosome, creating thirteen Y-deletant mouse models and conducting exhaustive reproductive phenotyping. Eight Y genes, including several that are deeply conserved and exhibit testis-specific expression, are dispensable for spermatogenesis. For others, we uncover novel functions, including a role for Uty in establishment and differentiation of spermatogonia, and for Zfy2 in ensuring meiotic pairing and reciprocal recombination between the sex chromosomes. We also generate the first mouse equivalent of the human infertility AZFa deletion, revealing cumulative detrimental effects of Y-gene loss on spermatogenesis. We use single nuclei RNAseq to identify candidate mechanisms by which Y genes regulate the germ cell transcriptome and reveal an unexpected impact of Y genes on testis supporting cells. Our study represents a paradigm for the complete functional dissection of a mammalian Y chromosome and advances our knowledge of human infertility and Y-chromosome evolution.

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Section: The Impact Of Y Genes On the Testis Transcriptomementioning

confidence: 70%

Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Subrini,

Varsally,

Balaguer Balsells

et al. 2024

Preprint

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“…The LH-R is located on the testicular membrane, serving as the exclusive binding site for LH. It activates the cyclic adenosine monophosphate (cAMP)/protein kinase A ( PKA ) signaling pathway on binding to LH-R [ 36 ]. The substrate PKA activates StAR , which facilitates the transfer of cholesterol into mitochondria and essential transcription factors that control the expression of genes related to steroidogenesis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic–Pituitary–Gonadal Axis

Sayed,

Zhang,

Tang

et al. 2024

Toxins

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Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

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“…Like many other tissues, gonads rely on endocrine, paracrine, and autocrine signaling to support gamete development, and their cells employ a variety of means to communicate with each other. For example, testosterone, produced largely in Leydig cells, diffuses into the testicular tubules where it binds to androgen receptors on Sertoli cells which then drive the production of factors that support spermatogenesis 53,54 . Progesterone, produced by follicular granulosa cells and corpora lutea, is critical for successful oocyte maturation and ovulation 55,56 .…”

Section: Discussionmentioning

confidence: 99%

The retrotransposon-derived capsid genesPNMA1andPNMA4maintain reproductive capacity

Wood,

Henriques,

Cullen

et al. 2024

Preprint

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The human genome contains 24 gag-like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the gag-like genes PNMA1 and PNMA4 support reproductive capacity. Six-week-old mice lacking either Pnma1 or Pnma4 are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. Analysis of donated human ovaries shows that expression of both genes declines normally with aging, while several PNMA1 and PNMA4 variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.

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Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis

Cited by 7 publications

References 211 publications

Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic–Pituitary–Gonadal Axis

The retrotransposon-derived capsid genesPNMA1andPNMA4maintain reproductive capacity

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