Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α.

In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1 + PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P < 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1 + PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1 + PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1 + PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1 + PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses.

Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows.

Loss of pregnancy can occur at many different stages of gestation and for a variety of causes but clearly produces a negative impact for reproductive and economic performances of dairy herds. This review describes four pivotal periods for pregnancy loss during the first trimester of gestation and discusses possible causes for pregnancy failure during these periods. The first period occurs during the first week after breeding with lack of fertilization and death of the early embryo producing major losses in pregnancy, particularly under specific environmental and hormonal conditions. In general, 20%-50% of high-producing lactating dairy cows have already experienced pregnancy loss during the first week of gestation with methods to decrease pregnancy loss during this period targeting improved oocyte quality by alleviating heat stress, inflammatory diseases, and body condition loss, and by increasing progesterone concentrations during preovulatory follicle development. The second pivotal period, from Days 8 to 27, encompasses embryo elongation and the classical "maternal recognition of pregnancy" period with losses averaging ∼30% but with surprising variation between farms (25%-41%). Maintenance of the CL of pregnancy is produced by the embryonic signal interferon-tau and alteration in uterine secretory patterns of prostaglandins F2α, E1, and E2. Failures or delays in trophoblast elongation and/or embryonic development result in loss of pregnancy during the second pivotal period possibly due to suboptimal histotroph. The third pivotal period is during the second month of pregnancy, Days 28 to 60, with losses of ∼12% based on a summary of published results from more than 20,000 pregnancies in high-producing dairy cows. Delays or defects in development of the chorioallantoic placentomes or embryo result in CL regression or embryo death during this pivotal period. Finally, a fourth period during the third month of pregnancy has reduced pregnancy losses (∼2%), compared with the first three periods but can be elevated in some cows, particularly in those carrying twins in the same uterine horn. Thus, there are varied causes for pregnancy losses during each pivotal period that correspond to key physiological changes in the embryo, uterine environment, and ovary. Similarly, strategies to reduce these losses are likely to require a multifaceted approach using rational methods that target the critical physiology in each pivotal period.