Female mice carrying a ubiquitin promoter-Insl3 transgene have descended ovaries and inguinal hernias but normal fertility.

Mouse knockout studies have indicated that Insl3 is involved in development of the gubernaculum in males, which is essential for normal testicular descent. To determine further the functions of Insl3 we have generated transgenic (TG) mice ubiquitously expressing Insl3. In these mice low levels of transgenic Insl3 mRNA are expressed in all tissues analyzed. In the TG females the ovaries descend to the base of the abdominal cavity during the fetal period, as a consequence of the formation of male-like gubernaculum structures. Furthermore, the gubernacular structures developed express androgen receptor, identically to the corresponding structures in males. At adult age the ligaments formed connect the uterine horns to the inguinal region of the abdomen. Ligaments are also formed between the lower and upper parts of the uterine horns, and these ligaments force the uterus to form a coiled structure. However, the TG females retain their reproductive functions, indicating that neither the location of the ovaries nor the macroscopic structure of the uterus is vital for reproduction. In addition, Insl3 expression causes inguinal hernia in females, suggesting that a combination of estrogen and Insl3 action disrupts proper development of the muscular and connective tissue structures of the abdomen. The lack of a phenotype in other tissues indicates that gubernaculum formation is the most sensitive biological response as regards Insl3.