330 Mechanisms of luteal formation and maintenance.

Abstract The corpus luteum (CL) is a transient endocrine gland that provides support for embryo implantation and placentation processes in mammalian species. While proper luteal formation is needed to ensure adequate production of progesterone (P4) to prepare the endometrium for the implanting embryo, understanding of processes involved in luteal formation and maintenance of the CL to ensure successful gestation remains incomplete. Failure to form an adequate CL is suspected as a causal factor in early pregnancy loss in many species, particularly in dairy cattle where it is implicated in as many as 65% of cases according to some reports. Studies conducted in nonhuman primates by Bishop et al. (2016) demonstrated by use of RNA silencing the role of the progesterone receptor PGR is conserved across species as critical for follicle rupture during ovulation (previously observed in pgr knockout mice/PRKO mice). In addition, knockdown of PGR in these rhesus monkey periovulatory follicles prevented the rise in luteal P4 observed during the early luteal phase, by blocking the rise of StAR and HSD3B2. This provided evidence that PGR directly regulates P4 synthesis in these luteinizing cells, a premise first proposed by Rothchild in the 1980’s following studies in rats. While similar studies have yet to be confirmed in ruminants, others have reported P4 regulates the expression of mRNA for StAR and HSD3B2 in bovine luteal cells, demonstrating this mechanism may also be conserved. As impaired luteal formation is implicated in pregnancy loss, some have attempted to provide exogenous P4 at time of insemination/embryo transfer, but variable success rates are reported from several, well designed studies. However, the CL produces additional factors beyond P4 alone that may be critical for successful implantation of the embryo and gestation. Besides P4, another major endocrine product produced by ruminant CL are prostaglandins (PGs). Two major PGs, PGF2alpha (PGF2A) and PGE2 are thought to act in opposition to each other, with PGE2 proposed to have luteotropic activities early in the luteal phase. This is gradually lost as the ratio of PGE2:PGF2A declines as the CL ages and becomes responsive to luteolytic PGF2A. The exact roles of PGE2 and PGF2A in luteal formation and early CL maintenance are still unknown, as well as any role for interactions between P4 and PGE2, or P4 and PGF2A. This presentation will describe the known effects of P4 and PGs in luteal formation and maintenance in ruminant species and discuss findings by the authors suggesting that P4 may regulate luteal formation and function by moderating local actions of PGs in luteal cells of ruminants. These and similar studies have the potential to identify factors needed to reduce early embryonic loss in cattle, ultimately increasing reproductive efficiency.