Study Uncovers More Clues Regarding Male Infertility


Researchers have pinpointed the primary molecular and genetic switch that triggers the production of healthy male sperm, when the time is right.

The switch is Polycomb Repressive Complex 1 (PRC1), a protein complex that activates certain germline genes, and the manufacture of healthy sperm. Germline refers to a series of cells where each is developed from earlier cells in the series.

Male mammals are born with enough reproductive germline cells to help create fertile sperm, but the sperm is not fertile during childhood. That’s because PRC1 puts a damper on the activation of fertile sperm manufacture until a male reaches puberty.

In their laboratory study, the researchers were surprised to find the PRC1 protein complex altered when mice reached reproductive age. It sloughed off germline gene components that inhibit sperm creation, and substituted in a component called Sall4 to initiate fertile sperm production, or spermatogenesis.

In mice bred without PRC1 the animals had smaller testes and failed to produce healthy sperm, or offspring.

“A long-standing question has been how reproductive germline genes are activated in a precise and timely manner. Our study answers this fundamental question by identifying novel epigenetic machinery that directs timely activation of spermatogenesis,” said lead investigator Satoshi Namekawa, Ph.D., Division of Reproductive Sciences at the Cincinnati Children's Perinatal Institute. “This has a very high impact because we found that this repressor of sperm production, PRC1, has a new function by promoting gene activation to make sperm when the time comes.”

The researchers have yet to discover how or why PRC1 drops its suppressor role to become a sperm activator. Questions also remain about how lifestyle or environmental factors effect the suppression and activation of reproductive genes, and whether PRC1 or Sall4 might be reliable biomarkers for male infertility.

Since Namekawa and others have determined that disrupted reproductive germline cells can be passed on to future generations, the incentive for answering all remaining questions is strong.

Source: Science Daily
Photo credit: Christian Gonzalez


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