Experimental research on the morphofunctional differentiation of the rat ventral prostate: roles of the gonads at birth.

In the male rat, a dramatic increase in serum testosterone (T) of testicular origin occurs during the first few hours of postnatal life. This experiment sought to determine whether this increase affects the physiology of the adult rat ventral prostate. Male rats were castrated at the time of caesarean delivery performed at different precise stages between 21 days and 22 days of gestation (0h males). Newborn male rats were castrated after spontaneous delivery at 22 days of gestation at 6, 12, 24 or 48 h after birth. Some male rats were castrated at fetal stage 21 days 13-15 h and injected at the time of surgery with 1, 2.5 or 5 micrograms of testosterone propionate (TP). Control males were sham operated at fetal stage 21 days 13-15 h and castrated at 23 days postnatal. At 30 days of age, each male was given T replacement therapy through a T filled silastic capsule until the time of sacrifice at 100 days of age. Before T implantation at 30 days of age, castration at 0 h or 48 h after birth does not impair neither branching morphogenesis nor the organization of the prostatic acinus. In contrast, the histological structure of the ventral prostate of the 0 h males implanted with T from puberty on is greatly disturbed. Cribriform and severe atypic hyperplastic acini with various epithelial cell arrangements are common. The alveolar sheath of the prostatic glands and the interacinar stroma are enlarged. In acini with severe intraepithelial hyperplasia, the disorganized epithelium rests over a thick basement membrane that stains strongly for laminin. In some 0 h males, epithelial cells break through the periacinar fibromuscular sheath and invade the interacinar stroma. It is as though all the categories of cells comprising the ventral prostate were not programmed in the absence of neonatal androgens. The secretory activity and the expression of Prostate Binding Protein (PBP) are impaired in the ventral prostate of the 0 h males. Castration performed after 12 h after birth has no deleterious effect on either secretory activity or PBP expression. The critical period during which perinatal T affects the histological structure and the functional differentiation of the ventral prostate extends from fetal stage 21 days up to 1 or 2 days postnatal. A single injection of 2.5 micrograms TP, a dose which mimicks the postpartum T surge is sufficient for programming the histological structure and the functional differentiation of the adult ventral prostate.