Project 1: Diet and Exercise Modulate the Sperm Epigenome in Men
Project 1: Diet and Exercise Modulate the Sperm Epigenome in Men
This is a controlled, randomized clinical trial to show that diet, exercise training, and
 their combination in overweight, physically inactive men will alter epigenetic programming to
 create a "healthy" sperm epigenome.
The investigators will recruit 20 normal weight, active men and 80 obese, inactive men to
 compare their sperm epigenome at their baseline state.

 The investigators will randomize the 80 obese, inactive men to intervention or no
 intervention for 12 weeks:1) observation with clinic visits; 2) low fat/low caloric diet; 3)
 supervised periodized strength and endurance training; and 4) low fat/ low caloric diet plus
 exercise training. The investigators will compare changes in their sperm epigenome within
 each group before and after intervention, between groups after intervention including the
 non-obese,active men at baseline.

 The investigators will follow the 80 men in the intervention groups and re-examined their
 sperm epigenome at 12 weeks and then another 24 weeks after cessation of treatment.
Inclusion Criteria:

 1. Male volunteers in good health as confirmed by physical examination, medical history,
 and clinical laboratory tests of blood and urine within the reference range at the
 time of screening

 2. Must have Hispanic Father and Mother from Mexico or Central America

 3. Normal weight, active subjects:

 -  BMI 18.5 - 24.9 calculated as weight in Kg/ (height in cm)2

 -  Participates in ≥150 min/week of moderate intensity physical activity as assessed
 by accelerometer

 -  Consume < 30% of calories as fat/day

 -  Fasting lipid panel within reference range or not clinically significant above
 the reference ranges

 Obese and physically inactive subjects:

 -  BMI ≥ 30 calculated as weight in Kg/ (height in cm)2 in obese subjects

 -  Have risk factors for developing type 2 diabetes (first degree relatives with
 DM2, BP≥130/80, HDL-cholesterol ≤ 35mg/dL or triglycerides ≥200mg/dL, fasting
 plasma glucose ≥100mg/dl to 125mg/dL or HgbA1c ≥ 5.7 to 6.4%, abnormal liver
 transaminases (not more than 3 times upper limit of normal suggestive of hepatic
 steatosis)

 -  Participates in ≤150 min/week of moderate intensity physical activity

 -  Consume >30 % fat as calories/day

 -  Stable weight for past six months prior to the first screening visit

 -  Willing to commit to 12 weeks of three times a week personalized exercise
 training

 -  Willing to commit to 12 weeks of weight loss diet (low fat and low calories)

 4. In the opinion of the investigator, subject is able to comply with the protocol,
 understand and sign an informed consent and HIPAA form

 5. Does not meet any of the exclusion criteria.

 Exclusion Criteria:

 1. Men who meet any of the following criteria are NOT eligible for enrollment in the
 trial:

 2. Men participating in another clinical trial within the last 30 days prior to the first
 screening visit

 3. Men not living in the catchment's area of the clinic or within a reasonable distance
 from the site

 4. Clinically significant abnormal findings at screening except for those stated above
 for the obese, inactive group

 5. Abnormal serum chemistry values, according to local laboratory normal values that
 indicate chronic liver or kidney dysfunction or that may be considered clinically
 significant (except for obesity related abnormal laboratory tests including blood
 glucose, Hgb A1c, liver transaminases, lipids for the obese, active group as stated
 above). Other abnormal lab values may also be exclusionary, at the discretion of the
 investigator

 6. Sperm concentration below 15 million/mL in more than one of three screening samples

 7. Diastolic (D) blood pressure (BP) > 30 and Systolic (S) BP > 130 mm Hg for the
 healthy, non-obese and active group; and diastolic (D) blood pressure (BP) > 150 and
 Systolic (S) BP > 100 mm Hg for the obese, inactive group on in the opinion of the
 investigator not suitable for exercise training (BP will be taken 3 times at 5 minute
 intervals and the mean of all measurements be considered)

 8. History of hypertension, including hypertension controlled with treatment in the
 healthy, active group

 9. Known history of reproductive dysfunction including vasectomy or infertility

 10. Known history of cardiac, renal, hepatic, cardiac or respiratory disease

 11. A serious systemic disease such as diabetes mellitus defined by the American Diabetes
 Association or morbid obesity (body weight greater than 120% of ideal body weight or
 BMI limitation as above)

 12. Known or suspected alcoholism or drug abuse or chronic infections

 13. Serious digestive and/or absorptive problems, including inflammatory bowel disease and

 14. Chronic food intolerance or diarrhea that preclude adherence to the study diet.

 15. Cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude
 moderate physical activity.

 16. Psychiatric disorders (including eating disorders) or conditions that, in the opinion
 of the investigator, would preclude participation in the study intervention (e.g.
 untreated major depression or psychosis, substance abuse, severe personality
 disorder).

 17. History of other malignancies except: adequately treated non-melanoma skin cancer