Developmental aspects of bladder function.

A review was conducted of the current knowledge of fetal and postnatal development of autonomic bladder function in animals. Studies of fetal and neonatal bladder development have been done in many animal species. Development of normal bladder function requires coordination of a number of different systems and processes, and continues after birth during the early neonatal period. In many neonatal animals, micturition occurs only after stimulation of a perineal-to-bladder reflex triggered when the mother licks the perineal region, and bladder distension fails to stimulate micturition. Voiding resulting from the normal bladder-to-bladder spinobulbospinal reflex activated by bladder distension develops only slowly over the first few weeks of life as synaptic connections in the sacral parasympathetic nucleus mature. The neurogenic response of bladder strips from young neonates is more sensitive to inhibition by atropine than that of strips from older animals, suggesting that there are developmental changes in the contribution of non-adrenergic, non-cholinergic transmitters to the response of the bladder smooth muscle to intramural nerve stimulation. Release of acetylcholine from cholinergic nerves and the mechanisms required to transform muscarinic receptor stimulation into efficient bladder contraction and emptying are fully developed at birth, but contractile and relaxant responses to many other agonists, such as adenosine triphosphate and noradrenaline, are developmentally regulated. Changes in calcium influx and storage may be responsible for many of these changes. Fetal detrusor is exquisitely sensitive to nitric oxide. Electrical stimulation of precontracted fetal bladder strips causes relaxation, an effect that is not seen in adult tissues, and is decreased by inhibitors of the actions of nitric oxide. Development of bladder function occurs before the onset of puberty and therefore is not normally dependent on sex hormones. However, neonatal treatment with or depletion of sex hormones can modulate bladder function. In particular, alpha-adrenergic receptor-mediated contractile responses of bladder detrusor are increased by prepubertal castration, an effect that may result from increases in the density of alpha-adrenergic receptors and/or changes in alpha-adrenergic receptor subtype expression.