Sexual differentiation in litter-bearing mammals: influence of sex of adjacent fetuses in utero

Abstract

In rodents and swine, individual differences in a broad range of characteristics correlate with intrauterine position during fetal life. By identifying the intrauterine position of mice at cesarean delivery, we can predict reliably postnatal reproductive traits such as genital morphology, timing of puberty, length of estrous cycles, timing of reproductive senescence, sexual attractiveness, sexual behavior, aggressiveness, daily activity level, body weight and tissue enzyme activity in females; in males we can predict genital and brain morphology, sexual behavior, aggressiveness, daily activity level, body weight, and tissue enzyme activity. In mice, as in all mammals, male fetuses have greater concentrations of testosterone than do females. In addition, female mouse fetuses have greater circulating concentrations of estradiol than do male fetuses, a condition not found in all mammals. A mouse fetus positioned between males has greater concentrations of testosterone than does a fetus of the same sex positioned between females, and a fetus positioned between females has greater concentrations of estradiol than does a fetus of the same sex positioned between males. Gonadal steroids regulate differentiation of secondary sexual characteristics. Studies in which the effects of intrauterine position have been eliminated by exposing fetuses to steroid receptor blockers reveal the critical role of steroids in mediating this phenomenon. The intrauterine position phenomenon provides the only mammalian model for relating postnatal traits to concentrations of endogenous hormones to which individuals are exposed during fetal life. Results from studies using this naturally occurring experimental system in litter-bearing species have given insights concerning the consequences of individual differences in steroid concentrations during sexual differentiation that likely apply to all mammals. One specific hypothesis is that circulating estradiol may interact with testosterone in mediating some aspects of sexual differentiation in rodents and, thus, possibly in other mammals.