The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

Abstract

The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.

Figure 1

Schematic representation of human sperm cell and localization of several glucose transporter isoforms in the distinct parts of the spermatozoon, namely head (which includes the nucleus and acrosome) and tail (comprehending the midpiece, principal piece and endpiece). GLUT1: glucose transporter 1; GLUT2: glucose transporter 2; GLUT3: glucose transporter 3; GLUT5: glucose transporter 5; GLUT8: glucose transporter 8; GLUT9a: glucose transporter 9a; GLUT9b: glucose transporter 9b.

Figure 2

Epigenetic modifications occurring during spermatogenesis. DNA methylation occurs in mitotic germ cells, setting up the paternal specific imprints. Phosphorylation occurs in meiotic cells, assisting in both recombination and XY body formation. Ubiquitylation, sumoylation, and incorporation of the H2AZ and H3.3 variants are all involved in XY body formation. During spermiogenesis, hyperacetylation occurs to assist in the histone-protamine transition.