Prostaglandins and Boars

Livestock Update, November 2004

Mark J. Estienne and Allen F. Harper, Tidewater AREC

Introduction
The effective operation of a commercial stud requires that young boars be easily trained to mount an artificial sow and allow semen collection. Once trained, it is essential that boars consistently mount in an expeditious manner. Indeed, the efficiency of a stud is compromised when boars display a reluctance or refusal to mount an artificial sow.

On many swine operations, commercially-available prostaglandin products are used in attempts to expedite mounting behavior, as well as restore libido in boars displaying decreased sex drive. The objective of this paper is to provide a brief review of research that has focused on the effects of exogenously administered prostaglandins on sexual behavior in boars.

General Comments about Prostaglandins
Prostaglandins were first discovered in mammalian seminal plasma and it was believed that the compounds originated from the prostate gland. Thus, the substances were named "prostaglandins". Today, however, it is known that prostaglandins are produced by practically all tissues in the body.

Arachidonic acid is the fatty acid precursor molecule for synthesis of prostaglandins. There are at least six types of prostaglandins and these compounds have numerous physiological functions. For example, prostaglandin-E2 (PGE) lowers blood pressure. In contrast, prostaglandin-F2alpha (PGF) increases blood pressure. Prostaglandins stimulate smooth muscle contractions, are involved in lipid metabolism, and modulate inflammatory responses.

The prostaglandins also participate in a variety of reproductive processes. For example, PGF causes luteolysis, which is the destruction of corpora lutea. Corpora lutea are ovarian structures that secrete progesterone, a steroid hormone essential for the maintenance of pregnancy. In gestating sows, an injection of PGF causes luteolysis, which results in a decrease in blood levels of progesterone, pre-partum behavioral changes and ultimately, induced farrowing. In fact, the use of PGF for induced farrowing is the only use of the compound in swine actually approved by the U.S. Food and Drug Administration (FDA). The use of PGF for stimulating sexual behavior in boars is technically considered an "extra label" use and should only be done after consultation with a licensed veterinarian.

There are several commercially-available PGF products including dinoprost tromethamine (Lutalyse; Pfizer Animal Health), cloprostenol sodium (Estrumate; Schering-Plough Animal Health) and fenprostalene (Bovilene; Syntex Animal Health). Once in the blood, prostaglandins have a very short half-life and are rapidly degraded during passage through the lungs.

Prostaglandin-Induced Sexual Behavior in Boars: Mechanism of Action

Shown in Figure 1 is the hormonal control of reproduction in boars. In swine, gonadotropin-releasing hormone (GnRH) is released from an area of the brain called the hypothalamus. GnRH travels to the pituitary gland and there stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In boars, LH and FSH stimulate spermatogenesis and the secretion of testosterone and estradiol, two steroid hormones that together are responsible for maintenance of libido. Castration of adult, sexually experienced boars decreased sexual behavior within 30 to 60 days, an effect reversed by testosterone and estradiol therapy (Levis and Ford, 1989). Blood levels of estradiol increase with age in boars (Estienne et al., 2000) and is inversely related to the time required to mount and begin ejaculation once boars are in the presence of an artificial sow (Louis et al., 1994). Estradiol concentrations were higher in boars that readily mounted an artificial sow than in boars that refused to do so.

The mechanism by which prostaglandins may enhance libido in boars is not clear. One plausible hypothesis is that prostaglandins stimulate the testicles to release steroid hormones. In an experiment conducted by Fonda et al. (1981), however, testosterone secretion was not affected by prostaglandin treatment in boars. In that study, catheters were placed in the jugular vein of six, 8 to 9 month-old boars. Blood samples were collected at 30-minute intervals for 12 hours. After collection of the second blood sample, boars were injected i.m. with 20 mg PGF (n = 3) or saline (n = 3). Blood levels of LH and testosterone were similar for PGF-treated boars and controls throughout the sampling period. In contrast, PGF treatment resulted in robust increases in blood concentrations of prolactin and cortisol. The role, if any, of prolactin, a hormone produced by the pituitary gland, and cortisol, a hormone secreted from the adrenal gland, in controlling sexual behavior in boars has not been established.

Enhanced sexual behavior as a result of PGF treatment almost surely involves a direct or indirect stimulation of one or more areas of the brain. Although data in the boar are lacking, numerous areas of the brain are activated after i.m. treatment of sows with PGF. When cells are stimulated, there is an increase in FOS protein, the translated product of c-fos mRNA. Burne et al. (2002) conducted an experiment during which sows were treated i.m. with PGF (n = 6) or saline (n = 5). Sixty-five minutes after treatment, sows were killed and various regions of the brain were analyzed for c-fos mRNA. Compared with control sows, PGF-treated sows had significantly higher levels of c-fos mRNA expression in the cerebellum and several areas of the hypothalamus.

Figure 1. Hormonal control of reproduction in boars.

Sexual Behavior after Prostaglandin Treatment in Boars
For the purposes of this section, the effects of prostaglandin treatment on sexual behavior will be summarized for three different "classes" of boars: Sexually inexperienced boars, sexually experienced boars, and sexually experienced boars displaying decreased sex drive.

Sexually inexperienced boars. Equivocal data exists regarding the use of prostaglandins as a tool to stimulate libido in young, sexually inexperienced boars (Szurop et al., 1985; Wettemann et al., 1992; Estienne et al., 2001; Kozink et al., 2002). Differences in the results among studies could be related to genetics, age or weight of experimental boars, different prostaglandin therapies employed, or undetermined management factors.

Szurop et al. (1985) conducted a clinical trial investigating the effects of a PGF analog (cloprostenol sodium; Enzaprost-F; Chinoin) on the training of boars for semen collection. Dutch and Belgian Landrace, Large White and Duroc boars (n = 156), 7 to 7.5 months of age and weighing 242 pounds, were employed. Boars were housed at 30 studs under similar management conditions.

Boars were injected with PGF (25 mg) 30 minutes before being exposed to the artificial sow. A "success" was defined as a reaction time of 5 to 7 minutes or less, combined with erection and collection of semen. Over 90% of the boars were successfully collected during the first training session and 95% of the boars were collected during the second training session. Control boars were not included, but previous experiences at the studs revealed a minimum of 4 to 5 training sessions with reaction times varying from 20 to 30 minutes and an overall success rate of 70%.

Estienne et al. (2001) conducted an experiment utilizing six Landrace x Yorkshire boars, 9.6 months of age and weighing 423 pounds. Boars were moved to a semen collection pen twice weekly for 4.5 weeks (a total of 9 training sessions). None of the boars mounted the artificial sow during this preliminary period. Immediately before entering the collection pen for the tenth training session, each boar received an i.m. injection of 10 mg PGF (Lutalyse). All boars mounted the artificial sow and allowed semen collection. During the eleventh training session, all boars were successfully collected without first receiving an injection of PGF.

In contrast to studies demonstrating positive effects, Wettemann et al. (1992) reported that PGF treatment did not enhance sexual behavior in boars identified as lacking libido. In that study, Hampshire boars (6 months of age; n = 10) that consistently failed to mount an estrous gilt were utilized. Boars were given i.m. injections of saline, 10 mg PGF (Lutalyse) at one minute before exposure to an estrous gilt, or 25 mg PGF at 30 minutes before exposure to an estrous gilt. There were no effects of treatment on ano-genital sniffs, nose to nose contact, nosing the flank, proper mounts or completed matings.

Finally, Kozink et al. (2002) conducted an investigation during which Lean-type, terminal-line boars (National Pig Development, Roanoke Rapids, NC), 5.9 months of age and weighing 248 pounds, were used. Boars were moved twice weekly for 6 weeks to a semen collection room. Upon entering, boars received i.m. injection of either deionized water (n = 10) or PGF (Lutalyse) at doses of 5 mg (n = 10), 10 mg (n = 10) or 20 mg (n = 10). Boars received a libido score of 1 to 5: 1 = boars showed no interest in artificial sow, 2 = slight interest in artificial sow but did not attempt to mount, 3 = mounted artificial sow but did not display an erection, 4 = mounted the artificial sow and displayed an erection, but did not allow semen collection, or 5 = mounted the artificial sow and allowed semen collection. Average libido score for boars receiving 10 mg PGF (2.35) was significantly greater than for controls (2.14). The percentages of boars successfully trained for semen collection, however, was similar among treatments.

The researchers noted that PGF­treated boars exhibited several behaviors not associated with libido that were dependant on the dose of the substance administered. Mild and transient scratching of the face and neck with the hind legs was observed in boars treated with 5 or 10 mg PGF. Boars receiving 20 mg PGF responded with intense scratching of the face and neck with hind legs followed by a transient state of immobilization while standing. One boar vomited within 5 min of each injection of 20 mg PGF. Thus, it is doubtful that a higher dose of PGF (greater than 20 mg) would have increased the number of boars successfully trained for semen collection.

Sexually experienced boars. The effects of PGF treatment on the training of sexually active boars (i.e., boars experienced with natural mating) to mount an artificial sow and allow semen collection was investigated by Estienne and Harper (2000). Purebred Hampshire, Landrace and Yorkshire boars ranging in age from 1 to 4 years were used. Boars were moved to a semen collection pen twice weekly for 4 weeks (8 training sessions). Immediately after entering the collection pen, boars received i.m. treatment with 10 mg PGF (Lutalyse) (n = 7) or deionized water (n = 7). Eighty-six % of the PGF-treated boars mounted and allowed semen collection during the first exposure to the artificial sow and 100% of the PGF-treated boars were trained for semen collection by the end of the fourth training session. In contrast, only 29% of control boars were collected during the first training session and by the end of the fourth session only 57% of the controls had been trained. At the conclusion of the eighth training session, the three remaining untrained controls were administered PGF. Two of these boars subsequently mounted the artificial sow and allowed semen collection.

During the course of the experiment, reaction time, defined as the elapsed time between entering the collection pen and the start of ejaculation was greater for controls (628.4 seconds) compared with PGF-treated boars (267.4 seconds). Moreover, the number of false mounts, defined as mounting the artificial sow but not ejaculating, was greater for controls (3.9/session) compared with PGF-treated boars (0.6/session). There was no difference between treatments for the duration of ejaculation.

Estienne and Harper (2000) suggested that the use of PGF has potential for expediting the training of sexually active boars to mount an artificial sow for semen collection. Use of the substance could be advantageous for producers switching to artificial insemination and needing to train a battery of boars that were previously used for natural mating.

Sexually experienced boars displaying decreased sex drive. Szurop et al. (1985) reported that treatment with a PGF analog (Enzaprost) restored sexual behavior in older boars exhibiting low sex drive. Purebred Dutch and Belgian Landrace, Large White, and Duroc boars (n = 120) that were 3 years old and weighed 440 pounds were studied. Boars were classified as showing signs of reduced libido and received 25 mg PGF 30 minutes before collection time. Treatment with PGF restored libido and normalized reaction time in 95% of the boars.

Although hormone profiles were not determined in the study of Szurop et al. (1985), decreased sex drive may have been associated with low testosterone and estradiol secretion and despite a deficiency in endogenous testicular hormone release, PGF increased sexual behavior. Estienne et al. (2004) tested this hypothesis and determined the effects of PGF on sexual behavior in boars with suppressed blood concentrations of testosterone and estradiol.

Lean-type, terminal-line boars (National Pig Development), 2.3 years of age and subjected to a once weekly semen collection regimen, were utilized. On the day after semen collection at week 0, boars received a s.c. implant of a GnRH agonist (Ovuplant; 2.1 mg Deslorelin; Fort Dodge Animal Health, Fort Dodge, IA) or were sham-implanted. In male animals, continuous exposure to potent GnRH agonists has been shown to decrease LH secretion because the binding sites for GnRH on the pituitary gland become over-stimulated. Subsequently, testosterone and estradiol secretion is decreased (Vickery, 1986).

Beginning at week 1, boars implanted with the GnRH agonist received an i.m. injection of 10 mg PGF (Lutalyse) (n = 5) or saline (n = 5) upon entering the collection room. Sham-implanted boars received an i.m. injection of saline (n = 5). Blood was sampled and sexual behavior assessed at week 0 and week 5.

As expected, blood concentrations of testosterone and estradiol were decreased by the GnRH agonist. However, the number of boars ejaculating, time from entering the collection room to the first attempt to mount the artificial sow, time from entering to the start of ejaculation, and duration of ejaculation did not differ among groups. The number of false mounts (mounting artificial sow but dismounting prior to semen collection) was increased by the GnRH agonist, an effect reversed by PGF. The number of false mounts for each treatment group was as follows: Sham-implanted boars receiving saline, 1.0; GnRH agonist-treated boars receiving saline, 4.2; GnRH agonist-treated boars receiving PGF, 0.2.

Estienne et al. (2004) concluded that acutely suppressing concentrations of testosterone and estradiol will not abolish sexual behavior in boars, but leads to an increase in the number of unsuccessful mounts of an artificial sow. The number of false mounts can be decreased by treatment with PGF.

Effects of Prostaglandins on Semen Characteristics
Little research has been conducted to determine the effects of treatment with prostaglandins on semen characteristics in boars. Hemsworth et al. (1977), Hashizume and Niwa (1984), and Estienne and Harper (2000) reported that sperm concentration and total number of sperm cells tended to increase after i.m. treatment of boars with PGF. In contrast, Kozink et al. (2002) found no effect of PGF treatment on various semen characteristics. These studies were all limited by low numbers of experimental boars from which semen was collected.

Given that prostaglandins are used commercially to enhance sexual behavior, we thought it important to determine if there were consequences of repeated treatment with PGF on boar semen characteristics. Thus, we conducted an experiment, the objective of which was to determine the effects of repeated injections of PGF on semen and libido characteristics in boars (Estienne and Harper, 2004).

Lean-type, terminal-line boars (National Pig Development), that were 1.5 years of age and trained to mount an artificial sow and allow semen collection were used. Semen was collected once weekly from week 0 to 15 and on four consecutive days during week 16. Boars received an i.m. injection of 10 mg PGF (Lutalyse) (n = 11) or vehicle (n = 11) immediately before entering the collection room. For the weekly collections, there was no effect of treatment on semen volume, gel weight, sperm concentration, total sperm cells, the percentages of motile or morphologically normal sperm cells, sperm velocity, or the period from injection to the start of ejaculation. Treatment with PGF increased the duration of ejaculation (472.0 seconds and 280.4 seconds, for PGF-treated and control boars, respectively).

During the intensive collection period (week 16), semen volume, gel weight, sperm concentration, total sperm cells, the percentage of motile sperm cells and sperm velocity were similar between treatments. The interval from injection to the start of ejaculation tended to decrease (by 44%) during the intensive collection period in PGF-treated boars, but not in controls. Treatment with PGF increased the duration of ejaculation (459.1 seconds and 303.1 seconds, for PGF-treated and control boars, respectively). Thus, overall there were no exceptional positive or negative effects of long-term treatment with PGF on indicators of semen quality and libido in boars.

Summary
In some research studies, exogenous administration of prostaglandins has been demonstrated to enhance libido in sexually inexperienced boars, sexually experienced boars accustomed to natural mating, and in sexually experienced boars exhibiting a loss of sex drive that was perhaps due to decreased blood concentrations of testosterone and estradiol. In other experiments, however, prostaglandin therapy has proven ineffectual in stimulating libido. Differences in the effectiveness of prostaglandin therapy to stimulate sexual behavior among studies could be related to genetics, age or weight of boars, different products or doses of products employed, or some undetermined management practices. Given the variability in the results, we suggest that the compounds should not be used routinely, but rather judiciously as a potential tool for enhancing libido in certain situations such as the training of boars to mount an artificial sow for semen collection. The physiological mechanism by which exogenously-administered prostaglandins stimulate sex drive remains undetermined but probably involves a stimulation of areas of the brain involved in reproductive behavior. Finally, available data suggests that there are no dramatic effects of exogenous prostaglandin administration on semen characteristics in boars.

Literature Cited
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