Endocrine Abstracts

Members of the TGF-β superfamily of ligands signal through a combination of Type I and Type II receptors. Type I and Type II receptors have been related to various human diseases including developmental malformation, cancers and endocrine disorders. However, little is known about the function of ALK7, a Type I receptor expressed in prenatal and adult CNS and various endocrine tissues. We have generated a mice lacking ALK7, which are viable and fertile but display metabolic and reproductive phenotypes. In the present study, we have analyzed the expression of ALK7 in different reproductive organs, the onset of puberty, and fertility in female mice lacking the receptor. Vaginal estrus cycles were monitored from postnatal day 30 to postnatal day 60. In mice lacking ALK7, the first vaginal estrus is delayed compared to wild type females. Also, during this peripubertal period, estrus cyclicity in knockout mice is delayed and irregular. Interestingly, body weight is increased in knockout female mice during the peripubertal period, but not at any other age. Mice that lack the ALK7 receptor develop reproductive defects, including fewer litters and pups per litter during their fertile period. In addition, knockout mice have a marked delay in producing their first litter. Puberty delay and subfertility in the ALK7 knockout females suggest an important role for ALK7 in puberty onset and maintenance of the reproductive function.