Prenatal Effect of Testosterone Propionate on the Differentiation of Sexual Functions in Rats

(I) Effect on the Pregnancy and Postnatal Development of the young

Abstract

Testosterone propionate (TP) was injected subcutaneously to pregnant rats at the later stage of gestation, and its effect on the differentiation of sexual functions of the offsprings were studied. The day in which sperm or plug was found in vaginal smear was designated as the 1st day of pregnancy. The successive injections were carried out once daily for 7 days from the 15th to the 21st day of pregnancy. The single injections were carried out on the 15th, 18th or 21st day of pregnancy. The dosages of TP were 0.05, 0.1, 0.5 and 5.0mg per pregnant rat a day in the case of successive injections and 5.0 and 10.0 mg per rat in the single injection. The results are summarized as follows :
(1) Except in only one rat receiving 5.0mg a day of TP, no parturition delay was observed in the pregnant rats injected with TP successively. The rats receiving the single injection of TP, however, demonstrated parturition delay when the administration was done on the 15th or the 18th day of pregnancy.
(2) Fetal resorbing activity of TP was observed in accordance with the increase of dosages in the successive injections and in the single injection on the 15th or the 18th day of pregnancy.
(3) The masculinizing effect of prenatal TP, administered either by single injection on the 18th day or by successive injections from the 15th to the 21st day of pregnancy, on the female fetuses was demonstrated in the ano-genital distance (AGD) of newborns on the day of their birth. The intensity of this effect was elevated with the increase of the dosages in successive injections. No remarkable change was observed in the AGD of male newborns.
(4) The prenatal effect of TP on the female AGD were still retained and rather extended even on the day of weaning, when administered by the successive injections at the dosages of 0.5mg a day or more or by the single injection on the 18th day of pregnancy. A single injection of 5.0 or 10.0mg TP on the 21st day of pregnancy did not affect the AGD of female newborns on the day of their birth, but gradually produced a masculinizing effect on female young and gave a significant enlargement of AGD when compared with the control on the day of weaning.
(5) The prenatal treatment of TP, 0.5mg a day for 7days (Day 15 to Day 21) or 5.0 or 10.0mg on the 21st day of pregnancy, produced not only delayed development of external genitalia of the young, but also caused abnormality in the female genitals. Female young had no vaginal openings, when their mother had received 5.0mg a day of TP from the 15th to the 21st day or 5.0 or 10.0mg of TP on the 18th day of pregnancy.
These results suggest that TP administered in latepregnancy not only influences directly the fetal genitals to cause masculinization of female offspring, but also affects the undifferentiated central nervous system of fetuses to produced delayed development or interruption of sexual maturity and function.