Project 1: Diet and Exercise Modulate the Sperm Epigenome in Men

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 Diabetes Mellitus type 2, 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