Comparative Analyses Reveal Conserved and Modified Steps in the Testis Descent and Scrotum Development in Mouse and Opossum.

\n<bold><italic>Introduction:</italic></bold> In many mammals, the testes descend from its abdominal position on the mesonephric kidney and are housed in the scrotum. It has been speculated that metatherians and eutherians might have acquired the scrotal testis independently because metatherians have the scrotum cranially to the phallus, while eutherians, such as humans and mice, possess it caudally. Rather, recent studies based on sequence comparisons of testis-descent-related genes indicate that the metatherian-eutherian common ancestor might already possess the descent mechanisms. To further elucidate the path of scrotal testis evolution, it is informative to compare the processes of the descent and scrotum development between metatherian and eutherian model animals. <bold><italic>Methods:</italic></bold> In this study, we histologically and molecularly compare these processes in gray short-tailed opossum (<italic>Monodelphis domestica</italic>), the most commonly used metatherian experimental model, and compare them with those in mouse. <bold><italic>Results:</italic></bold> Our observations indicate that, while transabdominal phase of the descent appears to be largely similar, scrotal phase differs due to their distinct scrotum positions. Our cell-labeling analyses and dynamic expression of <italic>Gsc1</italic> reveal extensive cell/tissue rearrangements in murine scrotal development. In contrast, <italic>Gsc1</italic> is not expressed in the developing genitalia and scrotal primordium of the opossum. <bold><italic>Conclusion:</italic></bold> Our results suggest recruitment of new regulatory pathways for the scrotum development and the scrotal phase of the testis descent during the evolution of eutherian mammals. In many mammals, the testes are housed into the scrotum. While marsupials, such as kangaroo and opossum, have the scrotum cranially to the phallus, placentals, such as human and mouse, have it caudally. In this study, we compare the process of testis descent and scrotum development in opossum and mouse. We show extensive cell/tissue rearrangements in the mouse scrotal development. Our results suggest recruitment of new regulatory pathways for the scrotum development and the testis descent during the evolution of placental mammals. [ABSTRACT FROM AUTHOR]