Recent advances, including the human genome project and numerous studies of cancer and other diseases, have shown that the genetic code is not simply limited to the sequence of the four bases of DNA but also includes epigenetic programming, heritable changes that affect gene expression [Riggs A, Martinssen R, Russo V (2007) Introduction. In: Riggs A, Martinssen R, Russo V (eds) Epigenetics mechanisms of gene regulation. Cold Spring Harbor Press, New York]. The science of epigenetics is important in understanding many diseases and biological processes, including in identifying the causes of disease and better understanding the mechanisms by which the environment can affect gene expression [Carrell Fertil Steril 97 (2):267-274, 2012]. This chapter will focus on the epigenome of sperm and particularly highlight the potential role of the sperm epigenome in embryogenesis.The sperm epigenome is unique and highly specialized because of the unique nature and function of sperm and because of the diverse requirements for successful fertilization. Due to the need for motility, sperm chromatin must be compacted and highly organized. During spermiogenesis the chromatin is packaged tightly into the sperm head by the replacement of most histones with protamines. This allows for protection of the DNA from the hostile environment in the female reproductive tract. Remaining histones can have chemical modifications to the tails of the protein that either facilitate or repress gene transcription. Sperm, like embryonic stem cells, have a unique pattern of histone modifications that includes both activating and silencing marks in the promoters of genes associated with development. These bivalent marks, along with DNA hypomethylation, comprise a unique state in which the key genes are "poised" for possible activation in embryogenesis. Sperm epigenetic abnormalities have been linked with multiple diseases including male factor infertility and poor embryogenesis.

There is currently no effective medical therapy for men with infertility due to oligoasthenozoospermia (OA). As men with abnormal sperm production have lower concentrations of 13-cis-retinoic acid in their testes, we hypothesized that men with infertility from OA might have improved sperm counts when treated with isotretinoin (13-cis-retinoic acid).We conducted a single-site, single-arm, pilot study to determine the effect of therapy with isotretinoin on sperm indices in 19 infertile men with OA. Subjects were men between 21 and 60 years of age with infertility for longer than 12 months associated with sperm concentrations below 15 million sperm/ml. All men received isotretinoin 20 mg by mouth twice daily for 20 weeks. Subjects had semen analyses, physical examinations and lab tests every four weeks during treatment. Nineteen men enrolled in the study. Median (25th, 75th) sperm concentration increased from 2.5 (0.1, 5.9) million/ml at baseline to 3.8 (2.1, 13.0) million/ml at the end of treatment (p=0.006). No significant changes in sperm motility were observed. There was a trend towards improved sperm morphology (p=0.056). Six pregnancies (three spontaneous and three from ICSI) and five births occurred during the study. Four of the births, including all three of the spontaneous pregnancies, were observed in men with improvements in sperm counts with isotretinoin therapy. Treatment was well tolerated. Isotretinoin therapy improves sperm production in some men with OA. Additional studies of isotretinoin in men with infertility from OA are warranted.

Climacturia is experienced by a substantial proportion of men after undergoing definitive treatment of prostate cancer. We found a complex relationship between stress urinary incontinence and climacturia, and noted that the presence of climacturia does not necessarily negatively impact sexual satisfaction.

SummaryThe significance qf these results is discussed.

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