Male Infertility, Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676
Conditions
Keywords
Sperm motility
Brief summary
The ability of sperm to swim is important for normal fertility. Men with a genetic variation in the gene coding for Choline Dehydrogenase (CHDH) have decreased energy production by sperm, and their sperm do not swim normally. The metabolic product of this gene is a nutrient called betaine (found normally in the diet as a part of many foods such as spinach, beets and grain products). This study tests whether treatment with betaine is safe and whether it can normalize energy production in sperm of these men and restore normal swimming ability.
Detailed description
Unidentified genetic aberrations such as single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic infertility in men. Choline dehydrogenase (encoded by CHDH) converts choline to betaine in the mitochondria. 5-9% of men have 2 alleles for a functional SNP in CHDH (rs12676), and they have low sperm adenosine triphosphate (ATP) concentrations with impaired sperm motility (asthenospermia) that should decrease fertility. Male mice in which CHDH is deleted also have very low sperm ATP, asthenospermia and are infertile. Supplementation of these mice with dietary betaine increases sperm motility and ATP concentrations. This purpose of this study is to conduct a phase I study of betaine treatment in men with 2 minor alleles for CHDH rs12676 to determine whether betaine supplementation is safe and to obtain preliminary data on the effects of betaine on sperm mitochondrial ATP concentrations and sperm motility in these men.
Interventions
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 - 60 year old men of multiple races and ethnicities * Estimated dietary intake of betaine of \<150 mg/day * Carrying two alleles of the rs 12676 single nucleotide polymorphism
Exclusion criteria
* Cystathionine-beta-synthase (CBS) deficiency * Currently taking betaine supplements * Currently receiving chemotherapy, radiation or any gonadotoxic drug * Female gender
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in sperm motility from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | Assessed using Computer-Aided Sperm Analysis methodology |
| Change in sperm count from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | — |
| Change in sperm mitochondrial function from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | Using Seahorse biochemical function assessment |
| Change in sperm ultrastructure from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | Using light and transmission electron microscopy |
| Change in sperm choline dehydrogenase concentration from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | Assessed by Western Blot analysis |
| Change in sperm betaine concentration from baseline | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in bilirubin concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in blood urea nitrogen concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Betaine intake | At screening and every 21 days during the study | Assessed using 3-day food records |
| Change in urinalysis parameters from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in creatinine concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in complete blood count from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in uric acid concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in alkaline phosphatase concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
| Change in aspartate transaminase concentration from baseline | At 0,10, 30, 50, and 75 days on treatment | — |
| Change in lactic dehydrogenase concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment | — |
Countries
United States
Outcome results
None listed