Ignite Creation Date:
2024-05-06 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04715828
Status:
UNKNOWN
Last Update Posted:
2021-01-20
First Post:
2021-01-15
Brief Title:
Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa
Sponsor:
University Hospital Clermont-Ferrand
Organization:
University Hospital Clermont-Ferrand
Study Overview
Official Title:
Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa
Status:
UNKNOWN
Status Verified Date:
2021-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Differentiated thyroid cancer is the third cause of cancer in young men of childbearing age Its treatment by irradiation with Radioactive Iodine 131 therapy RAT could alter spermatogenesis and result in azoospermia and permanent infertility A preventive gametes cryopreservation was recommended before RAT but without mentioning a period of teratogenic risk transmissible to the offspring To date RAT impact on human sperm nucleus is poorly known or even unknown notably on telomere length
Our objective is to define RAT effects on human sperm nucleus by in vitro irradiation exposure of human spermatozoa to mimicking that of the gonads in the context of irradiation with iodine131 used for thyroid cancer We will analyze standard sperm parameters major DNA alterations and telomere length using molecular and cellular assays Nucleus morphology and chromatin organization will also be analyzed using 3D bio-imaging This study will permit to optimize the indications for the preservation of fertility
Our objective is to define RAT effects on human sperm nucleus by in vitro irradiation exposure of human spermatozoa to mimicking that of the gonads in the context of irradiation with iodine131 used for thyroid cancer We will analyze standard sperm parameters major DNA alterations and telomere length using molecular and cellular assays Nucleus morphology and chromatin organization will also be analyzed using 3D bio-imaging This study will permit to optimize the indications for the preservation of fertility
Detailed Description:
Our main objective is to measure the in vitro impact of irradiation treatment on sperm nuclear quality such as DNA fragmentation and oxidation chromatin condensation and organisation nucleus morphology and notably sperm telomere length STL
The secondary objectives are
to measure RAT impact on sperm parameters vitality motility and morphology
to measure the impact of cryopreservation on chromatin organisation and nucleus morphology
to evaluate RAT impact on human sperm cells in comparison with cryopreservation
to evaluate the impact of different doses and types of irradiation on human sperm cells
to establish relations between potential alterations of standards sperm parameters vitality motility and morphology and nuclear sperm parameters DNA fragmentation and oxidation chromatin condensation and organisation nucleus morphology and STL
Our final goal is to provide a significant improvement of men fertility diagnosis and optimize our fertility preservation practices
To this end we will expose ejaculated human spermatozoa n 90 at different low and moderate doses of gamma or X photons to mimic gonads irradiation Absorbed doses by the samples were calculated using the GATE Monte Carlo platform version 82 Experiment geometry settings were modelled as three dimension voxelized volumes inside the software by assigning a shape size distance and density for all the volumes created All measurements will be made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine after receiving their written informed consent Semen samples are collected and subdivided into 3 arms to analyse sperm quality after
irradiation exposure 3 conditions
a freezing- thawing cycle
fresh state negative control without treatment
Before fresh state and after each treatment we will analyse
standard semen parameters vitality motility and morphology in accordance with WHO 2010
STL using Flow FISH q-PCR and q-FISH
chromatin condensation chromomycin A3
DNA oxidization 8-OHdG residues
DNA fragmentation TUNEL
3D nucleus structure using 3D bio-imaging
The secondary objectives are
to measure RAT impact on sperm parameters vitality motility and morphology
to measure the impact of cryopreservation on chromatin organisation and nucleus morphology
to evaluate RAT impact on human sperm cells in comparison with cryopreservation
to evaluate the impact of different doses and types of irradiation on human sperm cells
to establish relations between potential alterations of standards sperm parameters vitality motility and morphology and nuclear sperm parameters DNA fragmentation and oxidation chromatin condensation and organisation nucleus morphology and STL
Our final goal is to provide a significant improvement of men fertility diagnosis and optimize our fertility preservation practices
To this end we will expose ejaculated human spermatozoa n 90 at different low and moderate doses of gamma or X photons to mimic gonads irradiation Absorbed doses by the samples were calculated using the GATE Monte Carlo platform version 82 Experiment geometry settings were modelled as three dimension voxelized volumes inside the software by assigning a shape size distance and density for all the volumes created All measurements will be made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine after receiving their written informed consent Semen samples are collected and subdivided into 3 arms to analyse sperm quality after
irradiation exposure 3 conditions
a freezing- thawing cycle
fresh state negative control without treatment
Before fresh state and after each treatment we will analyse
standard semen parameters vitality motility and morphology in accordance with WHO 2010
STL using Flow FISH q-PCR and q-FISH
chromatin condensation chromomycin A3
DNA oxidization 8-OHdG residues
DNA fragmentation TUNEL
3D nucleus structure using 3D bio-imaging
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None