The luteo-placental shift, the guardian of pre-natal life.

Introduction The 'Iuteo-placental shift' is defined here as a shift in progesterone synthesis during pregnancy from the corpus luteum to the placenta. Distinct changes in the regulation of uterine function follow. It is predicted that this shift in the anatomical site ofhormone support, from an extrato an intra-uterine location, changes the distribution of progesterone, the character of the myometrial block and, therefore, uterine activity and reactivity. In different species the shift seems to occur at different times in gestation and to different degrees. It is these variations in the timing and the degree of the shift which best explain the noted 'species differences' in uterine activity. If so, 'species differences' are superimposed modifications, rather than fundamental alterations, of the basic regulatory mechanism of uterine function. The purpose of the shift is thought to be the protection of pregnancy beyond the life span of the corpus luteum, thus allowing continued pre-natal development. However, by weakening the progesterone block, the shift often permits a gradual early 'evolution' of uterine activity and reactivity long before term. If this 'evolution process' oversteps physiological limits a 'hostile' contractile environment develops, exposing the foetus to considerable hazards and, in extreme conditions, to prematurity and pre-natal defects. The experiments to be reported examine the merits of these concepts in the human, the rat and the rabbit. A critical survey of the current literature (Csapo & Wood, 1968) revealed that several maternal and foetal factors are implicated in the complex regulatory mechanism in control of uterine function during gestation and at labour. However, the contributions of these factors appear to differ in significance. The 'luteo-placental unit' dominates uterine function, for when its influence is complete it cannot be overruled by the others. Experiences with foetal death in utero and with the surgical separation of the 'foeto-placental unit', reveal that it is the placental, rather than the foetal component, which affects the myometrium directly. Foetal death has no acute, but only a chronic, influence on the continuation of pregnancy. The duration of gestation with a dead foetus seems to depend on the relationship between residual placental function and uterine volume. Within the 'luteo-placental unit' the placental component appears to be dominant, for it is indispensable in all species, while the luteal component is not. Even the rabbit, the champion of luteal dominance, requires placental support for the sustenance of the corpus luteum, an effect readily substituted for by estrogen therapy (Porter, Becker & Csapo, 1968). It is proposed to describe results obtained by multi-disciplinary teamwork in a series of experiments undertaken in the human female, the rat and rabbit in collaboration with a number ofinvestigators in my laboratory: Drs Abe, Kerenyi, Ogata, PintoDantas, Porter and Takeda, and in the steroidchemical laboratory of Dr Wiest.