Irradiated Semen Clinical Trial
Official title:
Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa.
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.
| Status | Recruiting |
| Enrollment | 200 |
| Est. completion date | January 1, 2022 |
| Est. primary completion date | January 1, 2022 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 18 Years to 45 Years |
| Eligibility | Inclusion Criteria: - Man less than 45 years - Man undergoing routine semen analysis at the Center for Reproductive Medicine, accepting the research protocol and signing the associated consent will be included in the protocol without distinction of physical criteria. Exclusion Criteria: - |
| Country | Name | City | State |
|---|---|---|---|
| France | CHU de Clermont-Ferrand | Clermont-Ferrand |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Clermont-Ferrand | Agence de La Biomédecine |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To measure in vitro the impact of an ionizing radiation treatment on sperm nuclear quality and in particular the size of telomeres. | To achieve this goal, we will expose human sperm to an irradiation dose of I131 to mimic the irradiation of gonads and sperm. Reliquat of semen will be cryopreserved (control condition). After thawing, the same sample will be subdivised into 2 groups in order to analyze the sperm quality :
After an irradiation dose of I131 After a cryopreservation |
01/01/2018-01/01/2022 | |
| Secondary | To measure in vitro the impact of an irradiation dose of I131 on sperm nuclear quality, notably on STL. | All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be 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: 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. |
01/01/2018-01/01/2022 | |
| Secondary | to measure RAT impact on sperm parameters (vitality, motility and morphology) | All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be 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. 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; |
01/01/2018-01/01/2022 | |
| Secondary | To measure in vitro the impact of cryopreservation on sperm nuclear quality, notably on STL, chromatin organisation and nucleus morphology | All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be 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: 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. |
01/01/2018-01/01/2022 | |
| Secondary | to evaluate RAT impact on human sperm cells in comparison with cryopreservation | We will compare effects induced by RAT and cryopreservation on each sperm sample. In order to limit the bias, for each irradiation treatment, a sample of sperm cells (cryopreserved control) will be treated under identical conditions. | 01/01/2018-01/01/2022 | |
| Secondary | to evaluate the impact of different doses and types of irradiation on human sperm cells | All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be 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. Irradiation exposure will be realised under 3 conditions: acute and low irradiation : sperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy. long and low irradiation: sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours. long and medium irradiation : sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours |
01/01/2018-01/01/2022 | |
| Secondary | 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. | We will correlate the effects induced by on vitality, motility and morphology and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL. | 01/01/2018-01/01/2022 |