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Research article
Sarah Rose Moore
The University of British Columbia
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4364-9128
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.
Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.
Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
Keywords
DNA methylation, puberty, epigenetic regulation, testosterone, gonadal hormones, sexual differentiation
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CURRENT STATUS: Published
View the published article at BMC Genomics.
Version 3
Posted 26 May, 2020
No community comments so far
Submission checks complete
On 19 May, 2020
Editorial decision: Accept
On 19 May, 2020
No comments provided
Editorial decision: Minor revision
On 11 May, 2020
Review #1 received
Received 06 May, 2020
Review #2 received
Received 14 Apr, 2020
Reviewer #2 agreed
On 13 Apr, 2020
Editor assigned
On 12 Apr, 2020
Reviewers invited
Invitations sent on 12 Apr, 2020
Reviewer #1 agreed
On 12 Apr, 2020
Submission checks complete
On 11 Apr, 2020
Editor invited
On 11 Apr, 2020
No comments provided
Editorial decision: Major revision
On 09 Feb, 2020
Review #2 received
Received 02 Feb, 2020
Reviewer #2 agreed
On 24 Jan, 2020
Review #1 received
Received 08 Jan, 2020
Reviewer #1 agreed
On 24 Dec, 2019
Reviewers invited
Invitations sent on 23 Dec, 2019
Editor assigned
On 27 Nov, 2019
Submission checks complete
On 26 Nov, 2019
Editor invited
On 26 Nov, 2019
First submitted
On 25 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
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See the published version of this preprint at BMC Genomics.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Sarah Rose Moore
The University of British Columbia
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4364-9128
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Genomics.
Version 3
Posted 26 May, 2020
No community comments so far
Submission checks complete
On 19 May, 2020
Editorial decision: Accept
On 19 May, 2020
No comments provided
Editorial decision: Minor revision
On 11 May, 2020
Review #1 received
Received 06 May, 2020
Review #2 received
Received 14 Apr, 2020
Reviewer #2 agreed
On 13 Apr, 2020
Editor assigned
On 12 Apr, 2020
Reviewers invited
Invitations sent on 12 Apr, 2020
Reviewer #1 agreed
On 12 Apr, 2020
Submission checks complete
On 11 Apr, 2020
Editor invited
On 11 Apr, 2020
No comments provided
Editorial decision: Major revision
On 09 Feb, 2020
Review #2 received
Received 02 Feb, 2020
Reviewer #2 agreed
On 24 Jan, 2020
Review #1 received
Received 08 Jan, 2020
Reviewer #1 agreed
On 24 Dec, 2019
Reviewers invited
Invitations sent on 23 Dec, 2019
Editor assigned
On 27 Nov, 2019
Submission checks complete
On 26 Nov, 2019
Editor invited
On 26 Nov, 2019
First submitted
On 25 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Genomics.
Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.
Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.
Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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