Developing a theoretical evolutionary framework to solve the mystery of parturition initiation.

Eutherian mammals have characteristic lengths of gestation that are key for reproductive success, but relatively little is known about the processes that determine the timing of parturition, the process of birth, and how they are coordinated with fetal developmental programs. This issue remains one of biology's great unsolved mysteries and has significant clinical relevance because preterm birth is the leading cause of infant and under 5 year old child mortality worldwide. Here, we consider the evolutionary influences and potential signaling mechanisms that maintain or end pregnancy in eutherian mammals and use this knowledge to formulate general theoretical evolutionary models. These models can be tested through evolutionary species comparisons, studies of experimental manipulation of gestation period and birth timing, and human clinical studies. Understanding how gestation time and parturition are determined will shed light on this fundamental biological process and improve human health through the development of therapies to prevent preterm birth.