Morphological Examination of the Corpora Lutea from Pregnant Bitches Treated with Different Abortifacient Regimes

Abstract

Different abortifacient regimes in dogs were analysed for their effect on the pregnancy corpora lutea (CL), namely, prostaglandin F2a analogue cloprostenol (CLO) combined with dopamine agonist cabergoline (CAB), or progesterone (P4) receptor antagonist aglepristone (AGL). Ovaries were collected after 6-10 days of treatment during first trimester. The CL of the control-group showed strong expression of relaxin (RLX), its receptor RXFP1 and enzymes of steroid biosynthesis (HSD) with high peripheral P4-levels. Whereas RXL, RXFP1 and HSD were lowest expressed in the CLO/CAB-group with a massive degeneration of CL and their blood vessels combined with low peripheral P4-level. The AGL-group showed less extensive CL degeneration and more intensive staining of the examined factors than CLO/CAB. In summary, all examined factors are associated with normal luteal function and are useful tools to stage luteolysis. Although both treatments have the same abortive action, their sequence of events on the CL is different.

Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation

“…It is likely that the majority of changes seen in pregnancy are driven by the hormones estrogen and progesterone ( 56 – 58 ). Increasing concentrations of both hormones positively correlate with increasing gestation and successful pregnancy ( 56 , 59 , 60 ). Estrogen has been shown to promote immune tolerance by inhibiting CD4 T cell expansion and promoting apoptosis, increasing Treg proportions, and promoting tolerant DC expressing inhibitory markers ( 61 – 63 ).…”

Progesterone-Related Immune Modulation of Pregnancy and Labor

“…Intriguingly, this is not evident in humans, and thus it is expected that a different mechanism of change in physiological P4 action is required to mediate human labor (15, 16). This has been supported by both animal and human studies that have used abortifacient regimens, either by (i) inducing a decline in systemic P4 levels, (ii) corpus luteum lysis or oophorectomy, or (iii) directly antagonizing the effects of P4 by the administration of an anti-progestin such as mifepristone (RU486) (17–22). It has been strongly suggested that the ability of RU486 to promote abortions and labor demonstrates such uterine processes are driven by “functional P4 withdrawal” in humans, which is mediated by altering the expression levels of P4 receptor (PR) isoforms and PR gene polymorphisms in reproductive tissues (23–25).…”

The Efficacy of a 3β-Hydroxysteroid Dehydrogenase Inhibitor for the Termination of Mid-Term Pregnancies in Dogs

“…Therefore, high P4 concentrations in bitches during AGL treatment can be considered normal. However, whereas some authors report that a significant increase in P4 concentrations occurs after the first AGL treatment [ 24 , 28 , 71 , 72 ], others report an insignificant change in P4 concentrations after AGL treatment [ 43 , 69 , 73 ]. In this study, the change in the P4 concentrations of the bitches treated with AGL was insignificant, and no increase occurred after the first AGL treatment.…”

“…However, it is well known that parturition and PT begin with prepartum luteolysis, which is characterized by a decrease in peripheral P4 concentrations and the downregulation of StAR and 3β-HSD expressions in luteal cells in response to an increase in PGF 2 α levels [ 13 , 74 ]. On the other hand, the decrease in P4 concentrations that triggers the mentioned regulatory pathway does not apply to AGL-induced parturition/PT [ 24 , 28 , 71 , 72 ] because AGL causes incomplete luteolysis [ 73 ]. Kowalewski et al [ 75 ] showed that blocking PGRs by AGL leads to the activation of the prostaglandin system in the luteal and placental tissues, with a similar occurrence during normal prepartal luteolysis.…”