IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY


nous oxytocin to mares around the time of luteolysis (ie, days 11 to 15 after ovulation) stimulates an immediate onset of PGF2secretion,31–33 when oxy- tocin is administered starting in the mid-luteal phase prior to the expected time of luteolysis (ie, before day 10 after ovulation), it does not induce PGF2 secretion and often paradoxically disrupts luteolysis causing prolonged CL function.32 Experimentally, continuous infusion of oxytocin


Fig. 1. Two glass balls manually recovered from the uterine lumen of a mare displaying signs of urogenital discomfort. The current owner was unaware these glass balls were present in the mare’s uterus. It is not known whether both glass balls were inserted at the same time or if one ball was placed initially and then at a later date the second ball was inserted without knowl- edge of the first one. Both glass balls had noticeable pitting on their surfaces, indicating it was likely that particulate matter from the glass balls had been deposited in the uterine lu- men. Photo courtesy of Dr Candace Jacobson.


Although placement of an intrauterine glass ball


has been the most widely used method of prolonging CL function in mares, there have been reports of deleterious consequences associated with their use, such as spontaneous fragmentation of the glass ball in the uterine lumen.28 Although that specific com- plication can be avoided by the use of a device made of an alternative material such as plastic,23 it is important to note that regardless of the composition of the device, if it is not eventually removed (spon- taneously or manually), some mares may retain the device for an extended period of time (ie, years), such that its presence in the uterine lumen may not be known to individuals working with the mare (Fig. 1). This has led to situations in which mares have been bred when an intrauterine device was present, and there are anecdotal reports of mares becoming preg- nant despite the presence of an intrauterine device and subsequently aborting because the device com- promised the pregnancy later in gestation. Be- cause of potential complications such as these, there is a need for alternative methods of extending CL function that are practical, efficacious, and safe.


5. Oxytocin Treatment


In contrast to the use of an intrauterine glass ball, administration of exogenous oxytocin during di- estrus is an alternative method of blocking luteoly- sis to prolong CL function. Endogenous oxytocin is involved in regulating PGF2 secretion from the endometrium during spontaneous luteolysis in the mare,29,30 and, although administration of exoge-


from day 8 to 20 after ovulation blocked luteolysis in four of five mares, whereas luteolysis occurred at the expected time in all four control mares that received saline infusion.34 Although it successfully induced prolonged CL function, continuous infusion of oxy- tocin would not be a practical method of long-term suppression of estrous behavior. As an alternative, in a “proof of principle” study, we showed that twice- daily intramuscular administration of 60 units (3 mL) of oxytocin on days 7 to 14 after ovulation was an efficacious method of disrupting luteolysis, be- cause it caused prolonged CL function through day 30 after ovulation in six treated mares, whereas six saline-treated control mares underwent luteolysis by day 16 after ovulation.35 In a subsequent study, we compared the use of the same 60-unit dose of oxytocin given intramuscularly twice daily versus once daily on days 7 to 14 after ovulation and found that CL function was maintained for 50 days after ovulation in five of seven mares (71%) treated twice daily, five of eight mares (63%) treated once daily, and one of seven (14%) untreated control mares.36 There was no difference (P  0.05) in the proportion of mares with extended CL function between once- and twice-daily administration of oxytocin, whereas collectively oxytocin treatment increased (P  0.05) the proportion of mares with extended CL function. Therefore, the oxytocin treatment protocol can be simplified to once-daily administration on days 7 to 14. In a third study, our objective was to monitor CL function and estrous behavior in mares for 90 days after administration of 60 units of oxytocin once daily on days 7 to 14 after ovulation.37 Two of nine control (22%) and six of nine oxytocin-treated (67%) mares had prolonged CL function (P  0.08). The mean duration of CL function in the two control mares with prolonged CL function was 78 days and in the six oxytocin-treated mares was 69 days. In both of the control mares and one of the six oxytocin-treated mares with prolonged luteal func- tion, estrus was not observed while progesterone remained above 1.0 ng/mL. For the remaining five oxytocin-treated mares with prolonged luteal func- tion, weak estrus was occasionally observed during the period of elevated progesterone. Although oxy- tocin treatment effectively prolonged CL function for approximately 2 months in two thirds of the treated mares, enigmatically, weak estrus was occasionally observed in some mares during the period of pro- longed CL function. Other research groups have recently evaluated modifications to the oxytocin protocol for prolonging


AAEP PROCEEDINGS  Vol. 59  2013 345


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