Production of Experimental Hypospadias in the Female Rat

Abstract

It has been reported that the injection of large amounts of estro-genic substances into the pregnant rat during the last few days of her pregnancy caused an “hypospadias” in the female offspring.¹,² This same abnormality resulted when the mother rat was injected with large doses during the first 4 days of lactation.³,⁴ It was also produced by direct injection of the female newborn.⁴

In the normal adult female rat the urethra opens at the apex of the clitorine prominence. In these abnormal animals the clitoris is widely split and the urethral meatus is immediately cephalad to the vaginal orifice. The lesion apparently involves the integrity of the urinary sphincter, as incontinence is usually present.

These findings have been confirmed during the course of a study on lactation. No effect has been noted in the male offspring. An attempt to produce the lesion in the female newborn by direct injection after the seventh day of life has been unsuccessful.

The animals treated to date fall into 3 groups. The first group consisted of 9 litters in which the mothers were injected with estrone in the postpartum period only. The mothers of 7 litters were injected with a total of 0.25 mg. each during the first 5 postpartum days. None of the female offspring had the abnormality. Two mothers were injected with 2.0 mg. during the postpartum period. One of these animals was given this dosage during the course of the first 5 days. None of her female offspring had the lesion. The other animal was given this dosage during the first 2 postpartum days. Three of her 4 female offspring had this lesion.

In the second group of animals treatment was given antepartum only. The abnormality was present in the 4 female offspring of one female that had 1.0 mg. during the 24 hours preceding delivery, and m the 5 female offspring of one animal that was given 2.0 mg/in the 48 hours preceding delivery.

In the third group the 10 mothers received treatment both ante and postpartum. The antepartum treatment varied. All except one animal received 0.1 mg. 2 times daily for the first 5 postpartum days. This one animal received twice this postpartum dosage. Of the 34 female offspring in these litters, the abnormality was present in 25.

Hypospadias has been produced so far in 37 female rats. Twenty-eight untreated litters have been observed specifically for this lesion. It has not been observed in any of the 128 female offspring of this group.

Inasmuch as the urethra of the newborn female rat opens immediately in front of the rectum and the clitorine prominence displays a grossly visible cleft, it is suggested that this abnormality represents an hypotrophic rather than a hypertrophic developmental defect.