PXD039802

PXD039802 is an original dataset announced via ProteomeXchange.

Title	Discontinuation of chronic delta-9-tetrahydrocannabinol diminishes impact on male fertility and the sperm epigenome in rhesus macaques
Description	Cannabis is commonly used amongst reproductive age males. Our group and others have shown that chronic delta-9-tetrahydrocannabinol (THC) use adversely impacts male fertility, but less is known about the potential reversibility of these changes. Our study’s objective was to determine if THC discontinuation mitigates THC-associated changes in male reproductive health using a rhesus macaque (RM) model of daily THC edible consumption over a 280-day period (4 spermatogenic cycles). Testicular volume, serum male hormones, semen parameters, sperm DNA fragmentation, seminal fluid proteomics, and whole genome bisulfite sequencing (WGBS) of sperm DNA were assessed at pre-THC, moderate-THC, and heavy-THC dosing, and at 70 and 140 days after THC discontinuation. Chronic THC use resulted in significant testicular atrophy, increased gonadotropins, decreased serum sex steroids, and increased DNA fragmentation. THC discontinuation led to partial recovery of testicular volume, sex steroids and sperm DNA integrity. Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. WGBS identified significant differential methylation in heavy-THC versus pre-THC sperm, with partial restoration of methylation after discontinuation of THC. Genes associated with differentially methylated regions (DMRs) were enriched for pathways involved in nervous system development and function. This is the first study demonstrating that chronic THC use in RMs adversely impacts male reproductive health, methylation of genes involved in development, and expression of proteins important for male fertility. THC discontinuation improves impacts to male fertility, including partial restoration of THC-associated sperm DMRs in genes important for development.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:15.516.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Macaca mulatta (Rhesus macaque); NCBI TaxID: 9544;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-02 08:23:04	ID requested
1	2023-05-18 14:27:00	announced
⏵ 2	2023-11-14 08:48:16	announced	2023-11-14: Updated project metadata.

Hedges JC, Hanna CB, Shorey-Kendrick LE, Boniface ER, Bash JC, Rice-Stitt TL, Burch FC, D'Mello R, Morgan TK, Lima AC, Terrobias JJD, Graham JA, Mishler EC, Jensen JV, Hagen OL, Urian JW, Spindel ER, Easley CA, Murphy SK, Lo JO, Cessation of chronic delta-9-tetrahydrocannabinol use partially reverses impacts on male fertility and the sperm epigenome in rhesus macaques. Fertil Steril, 120(1):163-174(2023) [pubmed]

submitter keyword: Cannabis, Quantitative proteomics,Male fertility, Seminal fluid, Rhesus macaque, Mass spectrometry, Isobaric labeling

Jamie Lo, MD MCR
contact affiliation	Division of Maternal Fetal Medicine Department of Obstetrics and Gynecology Oregon Health & Science University 3181 SW Sam Jackson Park Road, Mail Code L-458, Portland, OR, 97239, USA
contact email	loj@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039802
     1. Label: PRIDE project
     2. Name: Discontinuation of chronic delta-9-tetrahydrocannabinol diminishes impact on male fertility and the sperm epigenome in rhesus macaques