Acquisition of luteolytic capacity (ALC) is the developmental process by which the corpus luteum, which initially does not regress in response to prostaglandin (PG)F2A acquires this ability. Although the timing of ALC varies widely by species, it exists in all species in which it has been studied, including nonhuman primates, rodents, ruminants, and pigs. Because manipulation of the estrous cycle has been an essential part of reproductive management in livestock species, ALC has mostly been studied in ruminants and pigs, yet what information exists in nonhuman primate and murine models suggests that this is a mostly conserved process with only modest variation across species. Although there are substantial challenges to studying human luteal function, this luteal transition may also occur in humans. Critical regulators of acquisition of luteolytic capacity include both intracellular signaling mechanisms and cell-cell interaction networks. In luteal steroidogenic cells, signaling mechanisms downstream of the PGF2A receptor, including AMPK, and abundance and differential regulation of transcription factors appear to be critical regulators of ALC. Additionally, intraluteal prostaglandin synthesis and metabolism pathways are differentially regulated in CL of differing capacity to regress in response to PGF2A. Increasing luteal abundance of apoptotic regulators, or differential responsiveness of these to PGF2A, is also a crucial change that occurs during ALC. Finally, luteal vasculature, immune cell populations, and cytokine production are determinants of luteal PGF2A response. Understanding how the CL acquires the ability to regress will improve understanding of luteolysis and will lead to novel technologies to support luteal function and fertility.
Hughes-Brown et al. (Fri,) studied this question.