Luteolysis in the mare: a role for the immune system and gonadotrophins?

Abstract

The luteolytic process in the mare has been left relatively unexplored in recent times, while research has progressed considerably in our other domestic species. The role of the immune system in ovarian function has received increasing attention since the ovulatory process was first compared to an inflammatory reaction. The corpus luteum is highly vascular and hence large numbers of white blood cells circulate through it at all times. In addition resident populations of different immune cells have been identified in the CL of a number of different species throughout the oestrous cycle, with variations in these populations reported in association with key events such as ovulation and luteolysis. Initially attention focused on macrophages, whose only involvement was thought to be in clearing up damaged cells during structural regression. However, studies on other inflammatory cell populations have revealed that some of these, particularly lymphocytes, also vary with stage of the oestrous cycle, suggesting that they may play physiological roles in functional regression.

We investigated the presence, and changes in numbers, of populations of inflammatory cells in the equine CL at different stages of the oestrous cycle, after exogenous PGF2a administration to artificially induce luteolysis, and in early pregnancy. As found in other species, populations of cells did vary with stage of the cycle, and the selective infiltration of cytotoxic T -cells identified prior to functional luteolysis may indicate a role for them in this process. Changes in MHC class II expression by luteal cells, which could potentially instigate an immune reaction, were not identified in our study. Investigation of the chemoattractant properties of luteal tissue taken at comparable time -points, revealed that even by day 12 -14 of the cycle leucocytes were attracted to the CL. This increased after functional luteolysis, especially with regard to mononuclear cells, while PGF2a- treated tissue expressed even greater attractant activity. The identity of the chemoattractants was not determined, although collagen or collagenases may play a minor role.

Administration of GnRH analogues to cattle in dioestrus has been reported to prolong luteal function, and improve pregnancy rates to the preceding insemination. In attempting to create a model for prolonged luteal function in the mare, a GnRH analogue was administered, and endocrine and ovarian responses monitored. Treatment had no significant effect on oestrous cycle length, progesterone levels, or follicular dynamics. It did however significantly reduce oestradiol levels compared to control cycles. This may reflect altered folliculogenesis, which, in turn, could affect luteolysis. This was not detected in our study, and therefore did not provide us with a model for prolonged luteal function.

Treatment of mares with a GnRH antagonist during dioestrus has previously been found to attenuate progesterone levels, and cause premature luteolysis in treated animals, indicating a role for LH in supporting equine luteal function. We further investigated the role of gonadotrophins in equine luteal function by identifying and localising LH receptor mRNA expression in equine follicles and CL by in situ hybridisation. Expression was maintained in CL until functional luteolysis, after which it was considerably reduced. mRNA levels also remained high in CL of early pregnancy, while PGF2a treatment had varying results.

These findings demonstrate that cells of the immune system are potential key players in functional luteolysis in the mare, although their precise role requires further clarification. We have also shown that the CL produces chemoattractants to signal to these cells at the appropriate time, although the nature of these substances needs additional investigation. Gonadotrophins have also been identified as significant in luteal function, and our studies have indicated a means by which they may affect luteolysis. In addition we have definitively identified and localised sites of LH receptor mRNA in equine follicles and CL. More detailed studies of receptor expression in follicle populations prior to ovulation, and in different luteal cell populations, would help to further our knowledge of the equine CL, its formation and functions.