Studies on ovarian and uterine function in the mare

The submitted collection of papers represents iny work in the area of equine ovarian function and dysfunction. During spring transition, the endocrinological events responsible for recruitment of large anovulatory follicles appear to resemble recruitment of preovulatory follicles in the natural breeding season. These large follicles contain only low concentrations of progesterone and oestradiol. They have low expression of rnRNA encoding steroidogenic enzymes, have poor development of the tlieca interna and are poorly vascularised. These follicles are therefore showing signs of atresia while they are actively increasing in size. In preovulatory follicles, concentrations of inflammatory mediators increase as ovulation approaches, and fluid from preovulatory follicles is chemotactic for leucocytes. Intrafollicular treatment with indomethacin delayed ovulation which supports the central role for inflammation in the ovulatory process. It is also likely the matrix metalloproteinases are involved in the profound tissue remodelling that occurs around ovulation. Control of follicular growth has been studied and equine follicles are dependent on gonadotrophin stimulation when they reach 10 mm in diameter and on LH stimulation for final growth and maturation.The equine CL is dependent, at least in part, on trophic support by LH and luteal cells bind LH in vitro. Steroidogenesis in the CL varies before and after development of the endometrial cups in pregnancy. StAR protein increases after endometrial cup formation, allowing greater mobilisation of substrate for steroid synthesis. Although P450arom is consistently present in the equine CL, P450C17 increases after the endometrial cups form, allowing oestrogen synthesis by the CL in the pregnant mare. The cell types in the equine CL appear to cooperate in steroidogenesis, with P450Cn located in small luteal cells, and P450arom in large luteal cells. Maintenance of the CL in early pregnancy appears to be caused by the inhibition of endometrial PG synthesis by the conceptus. although the conceptus itself produces PGs. The demise of the CL involves apoptosis and is preceded by a decrease in angiogenesis. The immune system appears to play a significant role, with an influx of CD8+ lymphocytes into the CL prior to functional regression. At this time also, the CL is producing substances chemotactic for immune cells.Endometritis is the commonest cause of subfertility in mares. Mares prone to endometritis have low myometrial contractility compared with reproductively-normal mares and this appears to be due to a defect in the uterine oxytocin receptor or post-receptor mechanisms. The uterus has also been shown to be a source of oxytocin with the hormone located in secretory vesicles of the epithelium of the lumen and superficial glands. In mares with chronic uterine infection, chemotactic factors are present in uterine fluid that enhance the migration of neutrophils into the uterine lumen. However uterine fluid from infected mares interferes with phagocytosis and the opsonic activity of specific antibodies in the fluid is lower than that from reproductively-normal mares. Apart from a possible relative deficiency in numbers of macrophages, no abnormalities were detected in the cellular immune system in mares prone to endometritis.REFERENCES: 2.1 Watson ED, Barbacini S, Berrocal B, Sheerin O, Marchi V, Zavaglia G and Neechi D (2001) Effect of insemination time of frozen semen on incidence of uterine fluid in mares Theriogenology 56 123 -131 Initiator ofwork with clinical assistance • 2.2 Nikolakopoulos E and Watson ED (2002) Can uterine contractile activity be evaluated by transrectal ultrasonography? Theriogenology In Press Initiated work and supervised student • 2.3 Sertich PL and Watson ED (1992) Plasma concentrations of 13,14-dihydro-15- ketoprostaglandin F2a in mares during uterine involution Journal of the American Veterinary Medical Association 201 434-437 Supervised Dr Sertich and technician • 2.4 Watson ED, Buckingham J, Bjorksten TS and Nikolakopoulos E (2000) Immunolocalization of oxytocin and neurophysin in the mare uterus Journal of Reproduction and Fertility Supplement 56 289-296 Initiator and supervisor of work • 2.5 Bae S-E and Watson ED (2000) Immunohistochemical localisation of oxytocin and neurophysin in the equine endometrium using transmission electron microscopy 14th International Congress on Animal Reproduction, Stockholm abstr 1:49 Initiator and supervisor of work • 2.6 Nikolakopoulos E, Kindahl H, Gilbert CL and Goode J and Watson ED (2000) Release of oxytocin and PGF2a around teasing, natural service and associated events m the mare. Animal Reproduction Science 63 89-99 Initiator and supervisor ofwork. Prof Kindahl performed the PGFM assay. Dr Gilbert supervised the oxytocin assay • 2.7 Nikolakopoulos E, Kindahl H and Watson ED (2000) Oxytocin and PGF2a release in mares resistant and susceptible to persistent mating-induced endometritis Journal of Reproduction and Fertility Supplement 56 363-372 Initiator and supervisor of work. ProfKindahl performed the PGFM assay • 2.8 Bae S-E, Corcoran BM and Watson ED (2001) Organization of uterine innervation in the mare: distribution of immunoreactivities for the neuronal markers protein gene product 9.5 and PAN-N Equine Veterinary Journal 33 323-325 Initiator and cosupen'isor of work with Dr Corcoran • 2.9 Bae S-E, Corcoran BM and Watson ED (2001) Immunohistochemical study of the distribution of adrenergic and peptidergic innervation in the equine uterus and the cervix Reproduction 122 275-282 Initiator and co-supervisor of work with Dr Corcoran • 2.10 Nikolakopoulos E and Watson ED (1999) Uterine contractility is necessary for clearance of uterine fluid but not bacteria after bacterial infusion in the mare Theriogenology 52 413 -423 Initiator and supervisor of work • 2.11 Nikolakopoulos E and Watson ED (1997) Does artificial insemination with chilled, extended semen reduce the antigenic challenge to the mare's uterus compared with natural service? Theriogenology 47 583-590 Initiator and supervisor of work • 2.12 Nikolakopoulos E and Watson ED (2000) Effect of infusion volume and sperm numbers on persistence of uterine inflammation in mares Equine Veterinary Journal 32 164-166 Initiator and supervisor of work • 2.13 Watson ED (2000) Post-breeding endometritis in the mare. Animal Reproduction Science 60-61 221-232 • 2.14 Watson ED, Stokes CR, David JSE, Bourne FJ and Ricketts SW (1987) Concentrations of uterine luminal prostaglandins in mares with acute and persistent endometritis Equine Veterinary Journal 19 31 -37 My primary work with samples collected from cases by Mr Ricketts • 2.15 Watson ED, Stokes CR and Bourne FJ (1987) Cellular and humoral defence mechanisms in mares susceptible and resistant to persistent endometritis Veterinary Immunology and Immunopathology 16 107-121 My primary work • 2.16 Scudamore CL, Pemberton A, Miller HRP, McDonnell AM, Thomson SRM, Dawson A and Watson ED (1994) Measurement of equine alpha-1-proteinase inhibitor by ELISA in uterine flushings from mares Research in Veterinary Science 57 45-52 Supervised Dr Scudamore in collaboration with Professor Miller • 2.17 Watson ED (1987) Uterine defence mechanisms in mares resistant and susceptible to persistent endometritis: A review Equine Veterinary Journal 20 397-400 • 2.18 Watson ED and Dixon CE (1993) An immunohistological study of MHC Class II expression and of T lymphocytes in the endometrium of the mare Equine Veterinary Journal 25 120-124 My work with technical assistance • 2.19 Watson ED and Thomson SRM (1996) Lymphocyte subsets in the endometrium of genitally-normal mares and mares susceptible to endometritis Equine Veterinary Journal 28 106-110 My work with technical assistance • 2.20 Watson ED and Sertich PL (1992) Effect of repeated collection of multiple endometrial biopsy specimens on subsequent pregnancy in mares Journal of the American Veterinary Medical Association 201 438-440 My work with clinical assistance • 2.21 Watson ED, Stokes CR and Bourne FJ (1987) The influence of administration of ovarian steroids on the function of neutrophils isolated from the blood and uterus of ovariectomized mares Journal ofEndocrinology 112 443-448 My primary work arising from my PhD • 2.22 Watson ED, Stokes CR, David JSE and Bourne FJ (1987) Effect of ovarian hormones on promotion of bactericidal activity by uterine secretions of ovariectomized mares Journal ofReproduction and Fertility 79 531-537 My primary work arisingfrom my PhD • 2.23 Watson ED, Stokes CR and Bourne FJ (1988) Effect of exogenous ovarian steroids on concentrations of uterine luminal prostaglandins in ovariectomised mares with experimental endometritis Research in Veterinary Science 44 361-365 My primary work arisingfrom my PhD • 2.24 Watson ED, Stokes CR and Bourne FJ (1988) Influence of ovarian steroids on adherence (in vitro) of Streptococcus zooepidemicus to endometrial epithelial cells Equine Veterinary Journal 20 3 71 -3 72 My primary work • 2.25 Watson ED and Stokes CR (1988) Plasma cell numbers in uteri of mares with persistent endometritis and in ovariectomised mares treated with ovarian steroids Equine Veterinary Journal 20 424-425 My primary work • 2.26 Watson ED, Stokes CR and Bourne FJ (1987) The influence of arachidonic acid metabolites in vitro and in uterine washings on migration of equine neutrophils under agarose Research in Veterinary Science 43 203-207 My primary work arising from my PhD • 2.27 Watson ED, Stokes CR and Bourne FJ (1988) Concentrations of immunoreactive leukotriene B-4 in uterine lavage fluid from mares with experimentally-induced and naturally occurring endometritis Journal of Veterinary Pharmacology and Therapeutics 11 130-134 My primary work • 2.28 Scudamore CL, Pemberton A, Watson ED and Miller HRP (1993) Neutrophil chemotaxis in the horse is not mediated by a complex of equine neutrophil elastase and equine a-1-proteinase inhibitor British Veterinary Journal 149 331-338 Supervised Dr Scudamore in collaboration with Professor Miller • 2.29 Watson ED (1988) Opsonins in uterine washings influencing in vitro activity of equine neutrophils Equine Veterinary Journal 20 435-437 My primary work • 2.30 Watson ED and Stokes CR (1990) Effect of susceptibility to endometritis on specific antibody in the endometria of mares Theriogenology 34 39-45 My primary work • 2.31 Watson ED and Stokes CR (1988) Use of hyperimmune serum in treatment of endometritis in mares Theriogenology 30 893-900 My primary work • 2.32 Watson ED and Stokes CR (1988) Macrophage clearance of 125j_]abejie(j polyvinvyl pyrrolidone in the horse: Effect of ovarian steroids and persistent endometritis Equine Veterinary Journal 20 421-423 My primary work supervised by Professor Stokes • 2.33 Summerfield N and Watson ED (1998) Endometrial macrophage populations in genitally normal mares at oestrus and dioestrus and in mares susceptible to endometritis Equine Veterinary Journal 30 79-81 My work with technical assistance • 2.34 McDonnell AM and Watson ED (1993) The effect of dexamethasone sodium phosphate on mares with experimentally-induced endometritis Journal Equine Veterinary Science 13 202-206 Initiated and supennsed work • 2.35 Tomanelli RN, Sertich PL and Watson ED (1991) Soluble oestrogen and progesterone receptors in the endometrium of the mare Journal ofReproduction and Fertility Supplement 44 267-273 Initiated and supen'ised laboratory work by Ms Tomanelli. Clinical assistance from Dr Sertich • 2.36 Watson ED, Skolnik SB and Zanecosky HG (1992) Progesterone and estrogen receptor distribution in the endometrium of the mare Theriogenology 38 575-580 My work with technical assistance • 2.37 McDonnell AM and Watson ED (1992) The effect of transcervical uterine manipulations on establishment of uterine infection in mares under the influence of progesterone Theriogenology 38 945-950 Initiated and supervised work by Ms McDonnell • 2.38 Pedersen HG and Watson ED (2000) Uterine inflammation after intrauterine infusion with a low volume of Utrin Equine Veterinary Education 12 29-31 Initiator and supervisor of wor