<i>Ssm1b</i> expression and function in germ cells of adult mice and in early embryos

Ratnam, Sarayu; Bozek, Grazyna; Martin, Terence E.; Gallagher, Shannon J.; Storb, Ursula

doi:10.1002/mrd.22826

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Zfp982 has previously been shown to be involved in cell lineage differentiation in embryogenesis [ 58 ] and the 12-fold decrease in levels of this factor in our DKO mice may have significantly disrupted developmental processes. Zfp979 (also known as Ssm1b ) initiates DNA methylation and inhibits transcription in undifferentiated embryonic stem cells as well as in adult murine germ cells [ 59 ]. The 20-fold decrease of Ssm1b seen in our DKO testes could allow expression of a multitude of proteins detrimental to early development and germ cell maturation.…”

Section: Resultsmentioning

confidence: 99%

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

Sams

Mukai

Marks

et al. 2022

Reprod Biol Endocrinol

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Background Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. Methods Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. Results Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. Conclusions The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

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Section: Resultsmentioning

confidence: 99%

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

Sams

Mukai

Marks

et al. 2022

Reprod Biol Endocrinol

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“…Ssm1b was originally identified due to the differential methylation of the HRD transgene in B6J (methylated) and DBA (unmethylated) genetic backgrounds. In total, when maintained on an F1 background with DBA or SJL, the HRD transgene is methylated in seven strains of mice (C57BL/6J, FVB/NJ, C57L/J, LP/J, 129/SvJ, BALB/cJ, and A/J) and unmethylated in six strains of mice (DBA/2J, C3H/HeJ, SJL/J, CBA/J, SM/J, and AKR/J) [ 108 ]. The reference genomes for 16 strains were recently generated but there remain significant gaps in this region, likely due to the repetitive nature of the KRAB-ZFPs within this cluster, which are predicted to have arisen through segmental gene duplications [ 17 , 59 , 109 ].…”

Section: Lessons From Transgenesmentioning

confidence: 99%

Strain-Specific Epigenetic Regulation of Endogenous Retroviruses: The Role of Trans-Acting Modifiers

Elmer

Ferguson‐Smith

2020

Viruses

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Approximately 10 percent of the mouse genome consists of endogenous retroviruses (ERVs), relics of ancient retroviral infections that are classified based on their relatedness to exogenous retroviral genera. Because of the ability of ERVs to retrotranspose, as well as their cis-acting regulatory potential due to functional elements located within the elements, mammalian ERVs are generally subject to epigenetic silencing by DNA methylation and repressive histone modifications. The mobilisation and expansion of ERV elements is strain-specific, leading to ERVs being highly polymorphic between inbred mouse strains, hinting at the possibility of the strain-specific regulation of ERVs. In this review, we describe the existing evidence of mouse strain-specific epigenetic control of ERVs and discuss the implications of differential ERV regulation on epigenetic inheritance models. We consider Krüppel-associated box domain (KRAB) zinc finger proteins as likely candidates for strain-specific ERV modifiers, drawing on insights gained from the study of the strain-specific behaviour of transgenes. We conclude by considering the coevolution of KRAB zinc finger proteins and actively transposing ERV elements, and highlight the importance of cross-strain studies in elucidating the mechanisms and consequences of strain-specific ERV regulation.

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“…Finally, it was previously suggested that CRISP‐3 may modulate the activity of other genes either at the expression or at the functional level which, in turn, may control cell invasion in prostate cancer (Pathak et al ., ). This suggested gene expression modulation is important because alterations in gene expression can alter sperm function and quality (Castaneda et al ., ; Ratnam et al ., ). Indeed, in our study, varicocoele was associated with a decrease in seminal and functional quality of spermatozoa, when compared with controls group.…”

Section: Discussionmentioning

confidence: 97%

Cysteine‐rich secretory protein 3: inflammation role in adult varicocoele

et al. 2018

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Background: Cysteine-rich secretory protein (CRISP-3), a protein involved in inflammatory response, is highly increased in seminal plasma of adolescents with varicocoele and altered semen analysis, but not in adolescents with varicocoele and normal semen. It is not known, however, whether this increased seminal concentration occurs as an acute marker during the initial stages of varicocoele or whether this persists as an altered protein pathway. Objective: The purpose of this study, thus, was to test the hypothesis that this inflammatory state persists through adulthood and the correction of varicocoele could correct this state, by identifying the levels of CRISP-3 in seminal plasma. Materials and methods: This study was carried out in two substudies: (i) to verify the effect of varicocoele and (ii) to verify the effect of varicocelectomy on seminal plasma CRISP-3 levels. Seminal plasma CRISP-3 levels (29 and 31 kDa isoforms) were assessed for each provided sample using standard Western blotting. Results: The varicocoele group presented higher seminal levels of CRISP-3 when compared to controls, with a 67.5-fold increase in the unglycosylated isoform (29 kDa) and a 5.2-fold increase in the glycosylated isoform (31 kDa). In contrast, CRISP-3 levels decreased following varicocelectomy, both in the unglycosylated (5.6-fold decrease) and in the glycosylated (4.3-fold decrease) isoforms. Discussion: CRISP-3, a protein involved in inflammation, is increased in seminal plasma of men with varicocoele and this is partially reversed by varicocelectomy. Monitoring its seminal levels may be useful for assessing inflammation-related alterations to fertility in men with varicocoele. Conclusion: We conclude that, in the presence of varicocoele, there is a marked increase in seminal CRISP-3 levels. Surgical intervention (varicocelectomy) decreases CRISP-3 levels and improves semen quality.

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Ssm1b expression and function in germ cells of adult mice and in early embryos

Cited by 5 publications

References 43 publications

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

Strain-Specific Epigenetic Regulation of Endogenous Retroviruses: The Role of Trans-Acting Modifiers

Cysteine‐rich secretory protein 3: inflammation role in adult varicocoele

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