Mechanisms behind intrauterine device-induced luteal persistence in mares

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Abstract

Intrauterine glass balls are used to prevent oestrous signs in sports mares, but the mechanism of action is unknown. It has been suggested that the glass ball can mimic an embryo or act via an induced chronic uterine inflammation and absent or continuous low-grade prostaglandin (PG) release. The purpose of this study was to induce prolonged luteal function in mares using a small intrauterine device (IUD) and to study the mechanisms behind prolonged IUD-induced luteal function. A uterine swab and a biopsy specimen were obtained in early oestrus. A water-filled plastic ball, diameter 20 mm and weight 3.6 g, was inserted into the uterus 2–4 days after ovulation; the control mares underwent similar cervical manipulation without ball insertion. The mares were examined three times per week until day 23 and twice weekly thereafter until they returned to oestrus (transrectal palpation, ultrasonography and progesterone determination). The location of the IUD was recorded and ultrasound scans were video-recorded to assess the frequency of uterine contractions. When the mare returned to oestrus, a uterine swab and biopsy specimen were obtained and the bacteriological, cytological and histological (inflammation and glandular dilation) results compared with the samples obtained before the IUD insertion. The PG F metabolite levels were measured in the plasma of four control mares and eight IUD mares on days 11–16.

The IUD induced a prolonged luteal phase in 75% of the mares (9/12; IUD-P); the mean dioestrous length was 57.0 days. The three mares that did not respond to the IUD (IUD-N) showed a mean dioestrous length of 15.7 days and the 12 control mares 16.1 days. The inflammation and glandular dilation scores were not significantly different in pre- and post-manipulation biopsy specimens. Although locational changes of the IUD were observed, they occurred over very small distances and were mostly limited within the body-bifurcation area. The IUD-N and control mares showed increased uterine contractility 11–16 days post-ovulation, whereas the IUD-P mares did not. The control mares (n = 4) and IUD-N mares (n = 2) showed increased PG levels from day 14 post-ovulation, while the IUD-P mares (n = 6) showed basal levels only. We concluded that the IUD did not cause continuous PG release and suggest that close contact of the IUD with the endometrium may prevent the endometrial cells from releasing PGF.

Introduction

Strong oestrous signs are undesirable in sports mares, especially in competing animals. The most common treatment for aberrant or strong oestrous behaviour is the administration of progesterone or progestogen, but these need to be given constantly, otherwise the mare returns to oestrus in 2–5 days (Allen, 1984). In addition, the use of these hormones is forbidden in many countries of the European Union due to doping regulations.

The non-pregnant mare is unique in the capacity to prolong the luteal phase, e.g. after dioestrous ovulations (Stabenfeldt et al., 1974) or in experimental situations when human Chorionic Gonadotropin (hCG)-induced ovulations occur under progesterone influence (Daels et al., 1996, Kindahl et al., 2000, Hedberg et al., 2006). Most methods used to suppress oestrous behaviour are based on the artificial prolongation of the luteal phase. Oestrus can also be suppressed by non-pharmacological methods. Lefranc and Allen (2004) induced an extended luteal phase in mares by manual reduction of the conceptus between days 16 and 22 of pregnancy. Intrauterine devices (IUDs), small balls made of glass or other material are used by practitioners but their effect has been poorly documented. Nie et al. (2003) induced extended luteal phases in mares using 25- or 35-mm glass balls. These IUDs were effective in 11% of the cycles. Two unpublished student works from Denmark failed to show significant differences between controls and treated mares, using silver or glass balls (Meyer, 2003) or copper balls (Holm and Jespersen, 2003).

Luteolysis is accomplished by prostaglandin F (PGF) which is released from the uterus 14–15 days after ovulation (Neely et al., 1979). Spontaneous prolongation of luteal activity is a common phenomenon in mares occurring in 4–25% of cycles (Stabenfeldt et al., 1974, Hughes et al., 1975, Henry et al., 1981, Ginther, 1990). The reason is a failure to release adequate amounts of PGF at the normal time (Neely et al., 1979). The causes for prolonged luteal phases in non-pregnant mares include dioestrous ovulations, embryo loss after maternal recognition of pregnancy (pseudopregnancy), severe uterine damage, severe uterine infections, hysterectomy and idiopathic prolongation of the luteal phase (Ginther, 1990).

In pregnant mares, no PGF increase is observed in peripheral venous blood (Kindahl et al., 1982) or in uterine lumen (Zavy et al., 1984) from day 14 post-ovulation. In contrast to other domestic animal species, the equine embryo does not elongate, but remains spherical until the second month of pregnancy. During maternal recognition of pregnancy, the mobility of the early conceptus should prevent luteolysis and thus rescue the function of the primary corpus luteum. The small equine embryo remains mobile until day 16, traversing the entire uterus every 2 h (Leith and Ginther, 1985). The period of maximum mobility of the conceptus is temporally related to the inhibition of PGF release (Ginther, 1985). Embryonic mobility is thought to be an effective way of spreading a chemical signal, probably oestradiol, around the entire uterus (Vernon et al., 1981, Leith and Ginther, 1985).

Two hypotheses were proposed to explain the mechanism by which the IUD prolongs luteal function. One suggests that the device may induce mild inflammation of the endometrium, causing either a continuous release of small amounts of PGF or no release at all. Continuous release would diminish the amount of PGF so that there would not be enough PGF to achieve luteolysis. Another hypothesis suggests that the device could mimic a conceptus and prevent PGF release due to movement and physical contact of the IUD with the endometrium. However, the glass balls used moved very slightly (Nie et al., 2003).

The aims of the present study were to induce a prolonged luteal phase in mare, using small, light plastic balls and to elucidate the mechanisms for its action.

Section snippets

Animals

A total of 27 mares (Finnhorses, Standardbreds and warmbloods) from Equine College Ypäjä and MTT Agrifood Research, Ypäjä, Finland, was included in this experiment. The mares were 3–17 years of age (mean 9.4 years), had no history of reproductive failure and were clinically normal. They were age-matched in two different groups: the control group (n = 12) and the IUD group (n = 15). Three IUD mares did not finish the study: one because for expulsion of the IUD within 2 days after insertion, one for

Results

The IUD induced a prolonged luteal phase in 75% of the mares (9/12); the mean length of dioestrus was 57.0 days, and the mean IOVP was 61.4 days (Table 1). With the exception of one mare, no dioestrous ovulations were detected. This mare had two ovulations, on days 49 and 60.

Discussion

The IUD used in this study induced a prolonged luteal phase in 75% of the mares, whereas only 22% of the mares or the 11% of cycles were reported by Nie et al. (2003). The two experiments differed in the time of IUD insertion and removal, treatments in connection with insertion and the type of IUD. After insertion of the device, Nie et al. (2003) infused the uterus with 1 g of ticarcillin disodium in a 35-mL volume, whereas we performed no uterine treatments. They also administered 250 μg

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