Effects of intrauterine position on the behavior and genital morphology of litter‐bearing rodents

Male rats were exposed to prenatal or postnatal stress, or both. The prenatally stressed males showed low levels of male copulatory behavior and high rates of female lordotic responding. Postnatal stress had no effect. The modifications are attributed to stress-mediated alterations in the ratio of adrenal to gonadal androgens during critical stages of sexual differentiation. Specifically, it appears that stress causes an increase in the weak adrenal androgen, androstenedione, from the maternal or fetal adrenal cortices, or from both, and a concurrent decrease in the potent gonadal androgen, testosterone.

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.

Mice produce litters containing many pups, and the female fetuses that develop between male fetuses have significantly higher concentrations of the male sex steroid testosterone in both their blood and amniotic fluid than do females that develop between other female fetuses. These two types of females differ during later life in many sexually related characteristics. Thus, individual variation in sexual characteristics of adult female mice may be traceable to differential exposure to testosterone during prenatal development because of intrauterine proximity to male fetuses.