Perinatal development of gubernacular cones in rats and rabbits: Effect of exposure to anti‐androgens

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Abstract
In male rats gubernacular cones develop during the latter half of prenatal life. Inversion of these papilla-like organs after birth is the first step to postnatal growth of the muscular cremaster sacs. The factors regulating prenatal growth and differentiation or postnatal inversion of these gubernacular cones are unknown. The lack of a detailed and unequivocal description of the normal gubernacular cone growth is judged at least partially responsible for this ignorance. The present study therefore describes the normal development of the gubernacular cones in male and female rats from day 14 of fetal life. Androgens are hypothesized to control male gubernacular cone development but recent evidence throws doubt upon this proposal. Therefore, the second part of this study describes perinatal development of gubernacular cones in male rat foetuses exposed to the anti-androgen flutamide from day 10 after conception. Quantitatively normal growth occurred prior to birth, indicating no role of androgen in this process. Excessive growth in length was noticed during the neonatal period together with delay of gubernacular cone inversion. These developmental alterations did not represent direct anti-androgen–induced modifications of gubernacular cones development as the alterations were not observed in flutamide-exposed neonatally castrated animals. Failure of androgens to affect directly perinatal gubernacular cone growth could represent a rat-specific feature. Fetal rabbits show the development of similar structures during the second half of fetal life. The third part of this study examined the effect on the development of these structures of exposure of male and female foetuses to the anti-androgen cyproterone acetate. The latter compound inhibited male internal and external genital development but allowed unaltered gubernacular cone growth. The observations in this report thus present the normal pattern of perinatal gubernacular cone growth in rats together with evidence that these organs show male-specific growth independent of androgen. Further work should reveal the testicular or other factors responsible for this part of male bodily sexual differentiation processes.