The Shifting Role and Regulation of the Corpus Luteum in Vertebrate Reproduction: A Synthetic Review

Viviparity originated repeatedly by co-opting the ancestral luteal phase of the ovarian cycle. We argue that, in an evolutionary sense, pregnancy constitutes the serial homolog of the luteal phase. In this paper, we investigate what is known about the regulation and function of the corpus luteum and the luteal phase across vertebrates, covering pregnant and nonpregnant cycles when possible. Progesterone maintenance throughout gestation is a hallmark of placental mammals. However, as progesterone synthesis by the ovarian corpus luteum predates vertebrate viviparity, we must also consider its ancestral role beyond placental mammals. We show that the luteal phase length is still correlated to the evolution of gestation length, reflecting the common evolutionary history. Our approach suggests that the regulatory and variational decoupling of the pregnant from nonpregnant cycle was essential, as only after the two cycles became separately modifiable could gestation length increase to the extent it has in placental mammals. Mechanistically, this decoupling entails that the progesterone-dominated phase is extended beyond that of the nonpregnancy, usually through the so-called mechanisms for maternal recognition of pregnancy (MRP). Placental mammals achieved this in various ways, including prolonging the life span of the progesterone-producing corpus luteum, providing additional corpora lutea or extraovarian sources of progesterone, shortening the nonpregnant cycle, or through some combination of these mechanisms. We explore these underlying mechanisms for decoupling among the major eutherian lineages, and suggest that they originated independently. We conclude that eutherian gestation consists of parts that are not homologous across eutherians and that gestation length in placental mammals is not a trait that can be directly compared across species.