Impact of Metabolic Health on Sperm Epigenetic Marks in Humans

Eligibility Criteria

• * Male, age 18-65 years
• * Willing and able to provide informed consent and follow all study procedures, including providing sperm specimens 3 months apart.
• * Type 1 or type 2 diabetes diagnosis confirmed by an endocrinologist (for participants in the diabetes groups)
• * HbA1c \> 7% (for participants in the diabetes groups)
• * Overweight (BMI \> 25 kg/m2) (for all groups, to ensure groups are similar)
• * Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
• * Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin \< 3.0 g/dL; or serum bilirubin \> 2.0;
• * Severe diabetic retinopathy;
• * Congestive heart failure, New York Heart Association (NYHA) class II, III or IV;
• * History of myocardial infarction, unstable angina or revascularization within the past 6 months;
• * Active genitourinary infection;
• * Testicular volume \<12 mL (assessed using Prader orchidometer);
• * Hypogonadism, defined as total testosterone \<250 ng/dl;
• * Hyperprolactinemia, defined as prolactin \>18 ng/ml;
• * Hyperestrogenism, defined as estradiol \>42 pg/ml;
• * Cryptorchidism;
• * Cigarette smoking;
• * Active alcohol abuse or substance abuse;
• * Cancer (except localized non-melanoma skin cancers) or use of chemotherapy agents within 5 years;
• * Use of nitrates or guanylate cyclase stimulators;
• * Use of steroid hormones (including testosterone), other than inhalers for reactive airway disease