SpermatozoaNCT04159402
Dissect Assembly Rules of SPET12 Complex in the Mammalian Sperm
An observational study of Spermatozoa and Fertility, run by National Cheng-Kung University Hospital.
Trial summary
The sperm of the KO mouse shothe investigatorsd severe defects of all found compartments: acrosome, nucleus, midpiece and tail. The investigators also found SEPT12 co-localizes and interact with SEPT1, 2, 4, 6, 7, 10, 11, and 14 in sperm. Interestingly, some of these septins form filaments with SEPT12 in cells. Read more about this study
- Who is it for?
- Ages 20 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Spermatozoa, Fertility
- How many people
- 183 participants
- Where
- No sites listed yet
- Study dates
- Aug 2014to Jul 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: The participants were clinically diagnosed by semen analysis and further collected the normal human sperm.
Who may be able to join
- All participants signed a written informed consent form.
- Semen samples were obtained by masturbation after 3-5 days of sexual abstinence.
Who cannot join
- ．None
About this study
Official title: Medical Doctors(Department of Obstetrics and Gynecology)
The sperm of the KO mouse shothe investigatorsd severe defects of all found compartments: acrosome, nucleus, midpiece and tail. The investigators also found SEPT12 co-localizes and interact with SEPT1, 2, 4, 6, 7, 10, 11, and 14 in sperm. Interestingly, some of these septins form filaments with SEPT12 in cells. Based on these findings, it is hypothesized that (1) The core complex of SEPT12 filament consists of SEPT12-7-6-2-2-6-7-12; (2) Septin12 mutations, genetic variants, as the investigatorsll as haploinsufficiency disrupt SEPT12 filament and macro-complex; (3) Other SEPT's (e.g. SETP4, SEPT14) are also involved in the functionality of SEPT12; and (4) SEPT12 macro-complex is critical for compartment formation during terminal differentiation of male germ cells. The proposed study is designed to confirm the above hypotheses, to deconstruct mammalian SEPT12 complex, and to elucidate the functional significance of Septin12 mutations. In the proposed study, the investigators will use different methods, including proteomics, immunofluorescence assay, co- immunoprecipitation, pull-down assay, protein domain mapping, and protein complex fractionation to test the above hypothesis. The investigators have created a mouse carrying an important Septin12 mutation. In the proposed study, the investigators plan to knock out Septin14 in the mouse. SEPT14 interacts with SEPT12 and is also predominantly expressed in sperm. The mouse models and research tools could be used to explore the role of septins during spermiogenesis, to deconstruct the SEPT12 complex in the mammalian sperm, and to elucidate the functional significance of the Septin 12 mutations. Our findings may provide novel insight into the pathways human spermatogenesis, and has the potential to lead to development of therapeutic models for male infertility, and design of male contraceptives.
Read the detailed description
Redundancy and Interchangeability of Septins Septins 3, 4, 5, 6, 11, and 12 have been knocked out in the mouse model. Although SEPT4 abundantly expressed in different tissues, Septin4 KO mice only shothe investigatorsd male reproductive failure. SEPT12 is exclusively expressed in the post-meiotic germ cells, and Septin12+/- KO mice shothe investigatorsd spermatogenetic failure. In one study, SEPT5 deficiency decreased anxiety-related behavior, increased prepulse inhibition and delayed acquisition of rewarded goal approach, independent of mouse genetic backgrounds. In another study, Septin3-/- and Septin5-/-mice did not show any overt phenotypes. Knockout of a ubiquitously expressed septin, Septin6, also did not result in abnormal phenotypes. SETP11 is ubiquitously expressed, and Sept11 null mutation died in utero. The findings suggest redundancy and interchangeability of many septin family members. Among the septin family members, SEPT12 and 14 may deserve special attention for the reproductive biologists because they are mainly expressed in the testis.
- Conditions
- Spermatozoa, Fertility
What is being measured
The primary outcome is the main question the study is designed to answer.
Losses of SEPT12, SEPT7, SEPT6, SEPT2 and SEPT4 from the sperm annulus of a SEPT12D197N patient.
Immunofluorescence staining of normal sperm in a fertile control showed signals for SEPT12 . SEPT7, SEPT6, SEPT2 and SEPT4 (red) at the annulus. Also shown are merged fluorescence staining images with the additional staining of the sperm nuclei, as well as merged fluorescence staining images with merged brightfield images (BF merged). Blue color, DAPI stain; BF, brightfield only. Scale bar: 10 µm.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study startAug 2014
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SpermatozoaStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pao-Lin Kuo, MD, Principal investigator, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04159402
- Sponsor's protocol ID
- A-ER-102-438
- Status last verified
- Nov 2019
- First submitted
- 28 Oct 2019
- Last updated
- 4 Oct 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Medical Doctors(Department of Obstetrics and Gynecology)
- ClinicalTrials.gov ID
- NCT04159402
- Acronym / sponsor ID
- A-ER-102-438
- Conditions
- Spermatozoa, Fertility
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The sperm of the KO mouse shothe investigatorsd severe defects of all found compartments: acrosome, nucleus, midpiece and tail. The investigators also found SEPT12 co-localizes and interact with SEPT1, 2, 4, 6, 7, 10, 11, and 14 in sperm. Interestingly, some of these septins form filaments with SEPT12 in cells. Based on these findings, it is hypothesized that (1) The core complex of SEPT12 filament consists of SEPT12-7-6-2-2-6-7-12; (2) Septin12 mutations, genetic variants, as the investigatorsll as haploinsufficiency disrupt SEPT12 filament and macro-complex; (3) Other SEPT's (e.g. SETP4, SEPT14) are also involved in the functionality of SEPT12; and (4) SEPT12 macro-complex is critical for compartment formation during terminal differentiation of male germ cells. The proposed study is designed to confirm the above hypotheses, to deconstruct mammalian SEPT12 complex, and to elucidate the functional significance of Septin12 mutations. In the proposed study, the investigators will use different methods, including proteomics, immunofluorescence assay, co- immunoprecipitation, pull-down assay, protein domain mapping, and protein complex fractionation to test the above hypothesis. The investigators have created a mouse carrying an important Septin12 mutation. In the proposed study, the investigators plan to knock out Septin14 in the mouse. SEPT14 interacts with SEPT12 and is also predominantly expressed in sperm. The mouse models and research tools could be used to explore the role of septins during spermiogenesis, to deconstruct the SEPT12 complex in the mammalian sperm, and to elucidate the functional significance of the Septin 12 mutations. Our findings may provide novel insight into the pathways human spermatogenesis, and has the potential to lead to development of therapeutic models for male infertility, and design of male contraceptives.
Detailed description
Redundancy and Interchangeability of Septins Septins 3, 4, 5, 6, 11, and 12 have been knocked out in the mouse model. Although SEPT4 abundantly expressed in different tissues, Septin4 KO mice only shothe investigatorsd male reproductive failure. SEPT12 is exclusively expressed in the post-meiotic germ cells, and Septin12+/- KO mice shothe investigatorsd spermatogenetic failure. In one study, SEPT5 deficiency decreased anxiety-related behavior, increased prepulse inhibition and delayed acquisition of rewarded goal approach, independent of mouse genetic backgrounds. In another study, Septin3-/- and Septin5-/-mice did not show any overt phenotypes. Knockout of a ubiquitously expressed septin, Septin6, also did not result in abnormal phenotypes. SETP11 is ubiquitously expressed, and Sept11 null mutation died in utero. The findings suggest redundancy and interchangeability of many septin family members. Among the septin family members, SEPT12 and 14 may deserve special attention for the reproductive biologists because they are mainly expressed in the testis.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The participants were clinically diagnosed by semen analysis and further collected the normal human sperm.
Key inclusion criteria (2 listed)
- All participants signed a written informed consent form.
- Semen samples were obtained by masturbation after 3-5 days of sexual abstinence.
Key exclusion criteria (1 listed)
- ．None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Losses of SEPT12, SEPT7, SEPT6, SEPT2 and SEPT4 from the sperm annulus of a SEPT12D197N patient.
Time frame: 1 day
Immunofluorescence staining of normal sperm in a fertile control showed signals for SEPT12 . SEPT7, SEPT6, SEPT2 and SEPT4 (red) at the annulus. Also shown are merged fluorescence staining images with the additional staining of the sperm nuclei, as well as merged fluorescence staining images with merged brightfield images (BF merged). Blue color, DAPI stain; BF, brightfield only. Scale bar: 10 µm.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pao-Lin Kuo, MD principal investigator
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Spermatozoa and Fertility, run by National Cheng-Kung University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Losses of SEPT12, SEPT7, SEPT6, SEPT2 and SEPT4 from the sperm annulus of a SEPT12D197N patient. (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.