COMMENTARY--What signals testis descent?

Proper migration of the testes, from their original position adjacent to the kidneys to their final location within the scrotum, constitutes a normal and obligatory step of the male sex differentiation process. In humans and other mammals, the developing testis is connected to the abdominal wall by the cranial suspensory ligament and the gubernaculum. A peptide hormone called insulin-like 3 (INSL3) was found to be a master regulator of gonadal positioning in mammals by controlling gubernacular growth [1]. But key questions remained: How does INSL3 do it? What are the pathways activated by this hormone? In this issue of Biology of Reproduction, Johnson et al. have achieved an important advance in our understandings of testis descent by identifying several pathways activated by INSL3 in the gubernaculum. Theories behind testis descent In 1762 John Hunter published the first description of a structure, the gubernaculum, that "connects the testis with the scrotum and directs its course in its descent " [2]. Several hypotheses have been proposed over the past two centuries to explain the mechanism of testicular descent [3]. These theories included gravity, traction where growth of the gubernaculum pulls the testis down, propulsion where the testis is expelled from the abdomen by increased intra-abdomina