Purinergic signaling in testes revealed

Björkgren, Ida; Lishko, Polina V.

doi:10.1085/jgp.201611676

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…We also found an increased P2RX4 mRNA expression under SDSE, consistent with its reported high levels in juvenile mouse spermatogonia (Fleck et al, 2016). Although it cannot be known from this study, we speculate that P2RX4 mRNA levels reflected purinergic signaling, which is known to have broader endocrine effects including GnRH secretion and testosterone release from the testicular cells (Björkgren & Lishko, 2016;Fleck et al, 2016).…”

Section: Discussionsupporting

confidence: 88%

Transcriptome‐wide changes in testes reveal molecular differences in photoperiod‐induced seasonal reproductive life‐history states in migratory songbirds

Sharma

Das

Kumar

2019

Molecular Reproduction Devel

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We investigated the molecular basis of seasonal testicular states in black‐headed buntings (Emberiza melanocephala), in which seasonal migrations limit reproduction to a narrow time‐window during the year. We examined testicular gene expressions in buntings during short day‐induced photosensitive nonreproductive state (SDSE), and during long day‐induced early (LDES) and late (LDLS) gonadal maturation and regressed photorefractory (LDRF) seasonal states. Using Kallisto, we pseudoaligned the RNA‐Seq transcripts and calculated the transcript abundance. We found 1,799 differentially expressed genes (DEGs) between the four photoperiod‐induced seasonal states. Further pairwise comparison with SDSE revealed 1,187, 1,224, and 1,238 DEGs in LDES, LDLS, and LDRF, respectively; 852 genes were common to three comparisons. We then identified genetic pathways putatively involved in seasonal testicular cycle. DEGs that enriched calcium ion binding were highly expressed in testicular maturation states. Similarly, DEGs that enriched glycolytic pathway were highly expressed in LDES and LDRF states. More specifically, quantitative polymerase chain reaction showed significant differences between the photoperiod‐induced states in testicular expression of genes (HOOK1, RGS2, PRDX4, BCL6, CYFIP2, PDCD4, P2RX4, and GABRA1) involved in gametogenesis and associated pathways. Overall, these results show significant transcriptional differences, and provide insights into the molecular basis of seasonal changes in the reproductive life‐history states in a photoperiodic species.

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Section: Discussionsupporting

confidence: 88%

Transcriptome‐wide changes in testes reveal molecular differences in photoperiod‐induced seasonal reproductive life‐history states in migratory songbirds

Sharma

Das

Kumar

2019

Molecular Reproduction Devel

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“…Purinergic signaling is a critical component of testicular autocrine and paracrine communication ( 104 – 111 ). Different sets of purinergic receptors are expressed in the testis in a cell-specific manner, including Leydig cells ( 112 , 113 ), Sertoli cells ( 108 , 114 ), testicular peritubular cells ( 109 ), and pre- and post-meiotic germ cells ( 104 , 115 ) ( Figure 3 ).…”

Section: Purinergic Receptors In the Male Reproductive Tract And Matu...mentioning

confidence: 99%

Purinergic signaling in the male reproductive tract

et al. 2022

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Purinergic receptors are ubiquitously expressed throughout the body and they participate in the autocrine and paracrine regulation of cell function during normal physiological and pathophysiological conditions. Extracellular nucleotides activate several types of plasma membrane purinergic receptors that form three distinct families: P1 receptors are activated by adenosine, P2X receptors are activated by ATP, and P2Y receptors are activated by nucleotides including ATP, ADP, UTP, UDP, and UDP-glucose. These specific pharmacological fingerprints and the distinct intracellular signaling pathways they trigger govern a large variety of cellular responses in an organ-specific manner. As such, purinergic signaling regulates several physiological cell functions, including cell proliferation, differentiation and death, smooth muscle contraction, vasodilatation, and transepithelial transport of water, solute, and protons, as well as pathological pathways such as inflammation. While purinergic signaling was first discovered more than 90 years ago, we are just starting to understand how deleterious signals mediated through purinergic receptors may be involved in male infertility. A large fraction of male infertility remains unexplained illustrating our poor understanding of male reproductive health. Purinergic signaling plays a variety of physiological and pathophysiological roles in the male reproductive system, but our knowledge in this context remains limited. This review focuses on the distribution of purinergic receptors in the testis, epididymis, and vas deferens, and their role in the establishment and maintenance of male fertility.

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“…Changes in purinergic receptors has been investigated within sexes. For instance, changes in purinergic signaling response may be hormone-dependent ( 14 – 17 ) and they vary in the sex organs ( 18 – 20 ). Indeed, in a murine menopause model, ovarian protein levels of purinergic receptor P2X2 increased with ageing, suggesting that the P2X2 receptor is involved with menopause/ageing-related decline in ovarian function in females ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

Sex-related differences in the response of anti-platelet drug therapies targeting purinergic signaling pathways in sepsis

Amoafo

Entsie²,

Albayati³

et al. 2022

Front. Immunol.

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Sepsis, a complex clinical syndrome resulting from a serious infection, is a major healthcare problem associated with high mortality. Sex-related differences in the immune response to sepsis have been proposed but the mechanism is still unknown. Purinergic signaling is a sex-specific regulatory mechanism in immune cell physiology. Our studies have shown that blocking the ADP-receptor P2Y12 but not P2Y1 receptor was protective in male mice during sepsis, but not female. We now hypothesize that there are sex-related differences in modulating P2Y12 or P2Y1 signaling pathways during sepsis. Male and female wild-type (WT), P2Y12 knock-out (KO), and P2Y1 KO mice underwent sham surgery or cecal ligation and puncture (CLP) to induce sepsis. The P2Y12 antagonist ticagrelor or the P2Y1 antagonist MRS2279 were administered intra-peritoneally after surgery to septic male and female mice. Blood, lungs and kidneys were collected 24 hours post-surgery. Sepsis-induced changes in platelet activation, secretion and platelet interaction with immune cells were measured by flow cytometry. Neutrophil infiltration in the lung and kidney was determined by a myeloperoxidase (MPO) colorimetric assay kit. Sepsis-induced platelet activation, secretion and aggregate formation were reduced in male CLP P2Y12 KO and in female CLP P2Y1 KO mice compared with their CLP WT counterpart. Sepsis-induced MPO activity was reduced in male CLP P2Y12 KO and CLP P2Y1 KO female mice. CLP males treated with ticagrelor or MRS2279 showed a decrease in sepsis-induced MPO levels in lung and kidneys, aggregate formation, and platelet activation as compared to untreated male CLP mice. There were no differences in platelet activation, aggregate formation, and neutrophil infiltration in lung and kidney between female CLP mice and female CLP mice treated with ticagrelor or MRS2279. In human T lymphocytes, blocking P2Y1 or P2Y12 alters cell growth and secretion in vitro in a sex-dependent manner, supporting the data obtained in mice. In conclusion, targeting purinergic signaling represents a promising therapy for sepsis but drug targeting purinergic signaling is sex-specific and needs to be investigated to determine sex-related targeted therapies in sepsis.

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Purinergic signaling in testes revealed

Cited by 5 publications

References 47 publications

Transcriptome‐wide changes in testes reveal molecular differences in photoperiod‐induced seasonal reproductive life‐history states in migratory songbirds

Transcriptome‐wide changes in testes reveal molecular differences in photoperiod‐induced seasonal reproductive life‐history states in migratory songbirds

Purinergic signaling in the male reproductive tract

Sex-related differences in the response of anti-platelet drug therapies targeting purinergic signaling pathways in sepsis

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