One purpose of the Study of Pregnancy and Neonatal Health (SPAN) is to examine the role of paternal health factors in developmental origins of pregnancy and newborn health. Studies have shown that epigenetic marks (DNA methylation and small non-coding RNAs) in sperm is associated with fertility. Animal models have demonstrated that miRNA and other non-coding RNA from sperm can transfer paternal obesity, anxiety, and other exposures to genetically identical progeny. To interrogate biological mechanisms of paternal “programming”, SPAN is collecting semen samples from 760 men from 4 clinical sites in the next 5 years. For quality control, a pilot study of anonymous samples is being analyzed to ensure that the semen samples will be collected robustly at all sites. Three aliquots from each semen sample shall be preserved: 1) semen, 2) seminal plasma, and 3) motile sperm. The latter two fractions shall be isolated by a density gradient (Pure Sperm©) at the clinical site. Six anonymous collections shall be sent from each site. All samples shall be shipped on dry ice. For sperm, the protocol for preparing RNA extractions shall require pre-processing steps (e.g. somatic cell lysis buffer to remove any remaining somatic cells). Somatic cells provide the primary source of RNA contamination in sperm RNA analysis.