Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04159402
Other study ID # A-ER-102-438
Secondary ID
Status Completed
Phase
First received
Last updated
Start date August 2014
Est. completion date July 2017

Study information

Verified date November 2019
Source National Cheng-Kung University Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 183
Est. completion date July 2017
Est. primary completion date July 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 20 Years to 50 Years
Eligibility inclusion criteria: - All participants signed a written informed consent form. - Semen samples were obtained by masturbation after 3-5 days of sexual abstinence. exclusion criteria: .None

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
National Cheng-Kung University Hospital

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 1 day
See also
  Status Clinical Trial Phase
Withdrawn NCT02759705 - Bladder Exstrophy (FIVES FertIlity Vesical Exstrophy Sexuality)
Not yet recruiting NCT02534857 - A Study Comparing a Shorter Exposure of Oocyte to Spermatozoa Versus a Standard Incubation on the Live Birth Rate of In-vitro Fertilization Treatment N/A
Enrolling by invitation NCT01803893 - Prognostic Value of PIF Detection in Embryo Culture Media Correlation With Pregnancy Outcome N/A
Completed NCT01888744 - Preimplantation Genetic Diagnosis (PGD) With Gonadotropin-releasing Hormone (GnRH) Agonist Versus Antagonist Phase 4
Terminated NCT01173276 - Intrauterine Insemination In HIV-Discordant Couples N/A
Not yet recruiting NCT03680937 - Methods for Fertility Preservation: Impact of Vitrification on in Vitro Matured Oocytes
Completed NCT03455062 - Fertility Study of Women Who Received Organ Transplantation N/A
Completed NCT02736214 - Reproductive Life Plan-based Counseling With Men N/A
Completed NCT01895192 - Sperm Morphology by High Magnification in Fertility Men N/A
Terminated NCT01614704 - Impact of Sequential Chemotherapy on Young Patients Breast Cancer Treated Fertility
Terminated NCT01232972 - Oocyte Cryopreservation N/A
Terminated NCT01268592 - Fertility Preservation in Female Cancer Patients N/A
Completed NCT01012596 - Creighton Model Effectiveness, Intentions and Behaviors Assessment (CEIBA)
Completed NCT00390754 - Usefulness of Home Pregnancy Testing N/A
Completed NCT00231504 - Study of Follicle Stimulating Hormone (FSH) Receptor in Women With Low Antral Follicle Count Phase 1
Completed NCT03345264 - The Find Your PATHS (Pragmatic Assessment of a Tool to Help Survivors) to Sexual Health and Parenthood Study N/A
Recruiting NCT05414812 - Intervening on Women's Health for Rural Young Breast Cancer Survivors N/A
Active, not recruiting NCT02661932 - Fertility Preservation in Breast Cancer Patients Phase 4
Recruiting NCT06172504 - Ejaculation Frequency and Semen Parameters
Recruiting NCT02878434 - Fertility Preservation in Young Women With Cancer