CHAPTER 100 Induction of Estrus and Control of the Estrous Cycle in Swine
Despite many years of research investigating pharmacologic methods to control reproduction, swine producers and veterinarians are left with few options compared with those available for use in cattle. Nevertheless, the pharmacologic and managerial methods that have been developed have allowed for improved reproductive performance. Even so, estrous cycle control may not be practical or desired in all groups of swine, and pharmacologic methods must not be used to replace basic swine husbandry practices. Yet clear advantages are realized for swine producers who are able to control the timing of estrus and ovulation in large numbers of sows and gilts. Reproductive efficiency and improved economic return can be attained through maximizing the number of piglets weaned per sow per lifetime, reducing the number of nonproductive sow days, optimizing facility utilization for gilts, and reducing labor inputs. Although hormonal availability for control of pig reproduction varies throughout the world, most pharmacologic methods are similar and involve initiation of final follicular maturation, alteration of luteal lifespan, or synchronization of ovulation time. This chapter reviews the current knowledge of pharmacologic and management methodology for optimizing control of reproduction in the pig.
THE PREPUBERTAL GILT
Understanding the endocrine profile of the prepubertal gilt holds significance for influencing the timing of puberty and for developing technologies for inducing early reproductive function. Reproductive hormones originating from the hypothalamus, pituitary, and ovary regulate reproduction. Although hormones are synthesized and released by positive and negative feedback relationships in the mature female, in the prepubertal gilt the endocrine organs and their responsiveness to feedback are limited. Maturation is gradual and dependent on internal and external influences, some of which have yet to be identified. Endocrine control of ovarian activity occurs primarily through the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones control the processes of folliculogenesis and ovulation through their binding to receptors on the granulosa and theca cells of the ovarian follicle. Hormone binding stimulates a variety of activities including cell division, steroid synthesis, and follicle growth. Both hormones are controlled by hypothalamic gonadotropin-releasing hormone (GnRH) and by positive and negative feedback from ovarian steroids and the inhibin family molecules.
Immediately after birth, FSH, LH, and prolactin levels are elevated in circulation, but they gradually decline with age. This elevation is thought to occur because production mechanisms are functional, but feedback regulation has not yet developed. By contrast, circulating estrogen is low at birth but gradually increases with age in association with the increase in size and number of antral ovarian follicles.1 The hormone profile before pubertal estrus and during the subsequent cycle is not different from that in later cycles; accordingly, endocrine indicators of why gilts become reproductively active have been elusive. Immediately before pubertal estrus, however, plasma cortisol and prolactin are elevated, but these increases do not appear related to age at puberty. In gilts expressing first estrus between 183 and 225 days, progesterone has not been observed to be consistently elevated within the 6 days before pubertal estrus. No increase in estradiol occurs in the weeks preceding pubertal estrus except for the expected increase in estrogen that occurs before estrus. Of interest, some gilts have significant estrogen increases that last for days after exposure to a boar, but most fail to show estrus and have no detectable LH surge. The external symptoms of estrus such as vulvar swelling and mucous secretion are inducible at 150 days of age with exogenous estradiol. Sensitivity to estrogen may be underdeveloped in immature gilts, however, because low doses that produce physiologic symptoms of estrus in adult females are only partially effective in prepubertal gilts, despite the fact that all gilts exhibit an LH surge. LH level remains basal until the ovulatory LH surge at estrus. Therefore, attempts to advance age at puberty in the gilt by exogenous administration or selection of the aforementioned hormones probably are of little benefit.
Factors Influencing Attainment of Puberty in the Gilt
Gilts that express early puberty and are mated earlier produce more pigs per lifetime than those mated at later ages. Unfortunately, age at puberty can vary by 60 to 80 days for gilts that express estrus before 300 days of age. The factors influencing age at attainment include genetic composition.2 Differences within purebreds for age at puberty, however, can be as great as differences between breeds, owing to the different selection pressures from different genetic suppliers over time. It therefore becomes difficult to select purebred lines that have uniformly reduced age at puberty. Yet one of the most striking effects of breed on age at puberty is observed for the Meishan gilt, which reaches puberty at approximately 100 days of age, compared with 210 days for occidental breeds. Furthermore, offspring from matings of Meishan sires with crossbred occidental maternal line gilts show reduction in age at puberty and improved percentage of gilts expressing estrus, compared with females sired by occidental-breed boars.3 Despite these important observations, a majority of commercial maternal line genetics used today are the result of occidental multiple-breed crosses, and age at puberty in these lines indicates no advantage for reduced age at puberty.4 This finding is perhaps not surprising because most selection schemes for maternal lines do not include age at puberty.
Direct selection for reduced age at puberty has produced an estimated heritability between 0.11 for a single generation and 0.25 over multiple generations. Age at pubertal estrus can be reduced by −1.5 to −3 days in each generation with selection.5 Selection for age at puberty is desirable and is not associated with any reduction in litter traits. Research also has shown expression of early puberty is not dependent on boar exposure because early puberty lines lacking boar exposure still express earlier puberty compared with nonselected lines.6
The available information is conflicting regarding the importance of gilt body composition and its relationship to puberty. Liveweight explains 77%, tenth-rib fat 40%, and average daily gain less than 10% of the variation in age at puberty.7 It has been reported that gilts with more backfat thickness at 90 kg have more intense vulvar reddening and swelling at estrus, and gilts with strong vulvar symptoms are younger and lighter at estrus.8 Similarly, in selection experiments, gilts selected for early puberty also tend to cycle earlier and have more backfat than those gilts selected for later puberty. Therefore, selection for age at puberty and related traits of economic importance must become a greater priority in reproductive selection processes.
It is difficult to separate out the effects of nutrition from growth rate and body composition. Nutritional influences, however, can greatly influence the genetic potential to express growth and body composition traits. Of the numerous reviews on the effects of diet for the developing gilt, most agree that severe energy or nutrient restriction can delay or even prevent puberty, whereas minor restrictions may have little detrimental effect on measured reproductive traits. Furthermore, excess energy intake also has not improved reproductive performance. Increased protein, and specifically, certain amino acids, has resulted in some cases of improved reproduction, however. This infrequent outcome may result from the complex issues of amino acid ratios, protein-to-energy ratios, and variation in reproductive responses measured. Nevertheless, at present most experts agree that when energy is not limiting and protein is available for maximal lean tissue accretion, diet should not be limiting to reproductive performance.
Physical and physiologic maturity are reported to be more important for attainment of puberty than age, weight, and even boar exposure.9 Of all identifiable factors, physiologic age appears to hold the greatest relationship to the age at attainment of puberty. Physiologic age, more than chronologic age, is important because even though gilts can ovulate in response to exogenous gonadotropins and respond to exogenous estradiol with an LH surge after 100 days of age, strong evidence indicates that neither of these mechanisms is completely mature until after 160 days. This finding indicates that induction procedures should not be initiated too early.
The effect of season of birth on puberty is difficult to separate from the effects of temperature, light, and changing photoperiod during development. Some researchers, however, have shown that developing gilts during a shortening photoperiod (fall-winter) and maturing them under increasing light (spring-winter) induces a greater proportion of the animals into puberty than is observed with development of gilts during increasing photoperiod (spring-summer) and maturation under shortening photoperiod (fall-winter). Unfortunately, little evidence is available to suggest an overall advantage in earlier puberty by lighting regimen or type of light. Excessive darkness does delay estrus, however, and continuous light does not advance age at estrus when compared with shorter 8- to 16-hour intervals of light each day.
Although the issue is controversial, confinement has been shown in some cases to increase the proportion of anestrous gilts and to delay age at puberty by 3 weeks.10 The general consensus is that that gilts raised in restricted space may be less likely to express estrus at an earlier age. Mature gilts raised in only 1 square meter of space expressed estrus at a lower rate than that observed for animals allowed 3 square meters of space (79% versus 100%).11 The importance of small group size is unclear, but housing developing gilts in groups of less than 3 should be avoided, and little evidence is available to suggest an effect of housing 3 to 30 pigs per pen on age at puberty.
Boar exposure is an effective method for reducing age at puberty, inducing estrus, and improving estrus synchrony. The effect of boar exposure is presumed to be physiologic because it has been shown to transiently increase both LH and estradiol concentrations.12 Exposing gilts to boars between days 150 and 170 appears to be most effective for advancing age at puberty and results in the highest degree of estrus synchrony. Earlier boar exposure beginning at 70 days of age, when compared with no boar contact or boar exposure at 160 days of age, had no effect on advancing age at puberty, however. Exposure duration of 5 to 30 minutes each day appears equally effective for advancing age at puberty.13 Yet the proportion of females reaching puberty within 60 days from initiation of boar exposure at 160 days of age does improve as frequency increases between one and three times per day.14 Continuous boar contact appears to have little detrimental effect on age at puberty, except that it can make detection of estrus in gilts more difficult.
Greater response to boar exposure can be obtained when combined with transportation stress at 160 days. This regimen shows major response effects for boar contact alone but not for transport alone. Typically, the boar effect is not observed in the first week but is evident by 30 days. Transportation for 1 km or more in conjunction with boar exposure has the greatest impact on the proportion of females induced into puberty.15 To obtain optimal responses for estrus induction, physical contact with the boar is now recommended as superior to fenceline contact.16 Age of the boar also is important, because exposure to boars 11 months of age and older is more effective than exposure to those 6.5 months of age or younger. It also is unclear whether exposure to a second boar or exposure of gilts to estrous sows will be effective for influencing the proportion of gilts expressing estrus, even though age at puberty may be reduced.17
It is not known whether ovarian status affects age at puberty. Ovary classification before puberty at 150 days of age and at 5-day intervals thereafter shows ovaries with only small and those containing larger follicles.18 Of interest, the ovaries switched from one type to another over time, and no changes in circulating hormones were associated with any of these ovarian class changes. This evidence may suggest that follicle growth occurs in waves and that larger follicles in the prepubertal gilt undergo regression and do not undergo ovulation before puberty. The gilts with large follicles greater than 6 mm in diameter had a greater number of ovulations when compared with those with smaller follicles in response to human chorionic gonadotropin (hCG) given at 170 days of age.19 Ovaries containing larger follicles versus those with only small follicles, however, do not always show an overall advantage in response to gonadotropins on estrus induction response, even though an early puberty line with only large follicles at time of injection did respond at a higher level than the nonselected line containing large follicles.20 One explanation for this finding may be the observation that at 166 days in Large White gilts, only half of them have follicles (greater than 3.5 mm) that are responsive to hCG.21 Thus, differences in physiologic maturity appear to be regulated at the origin of the ovary and may explain why only some animals respond to exogenous hormones.
Exogenous Hormone Control
In the pig, equine chorionic gonadotropin (eCG), also called pregnant mare’s serum gonadotropin (PMSG), is the most commonly used and most effective product for induction of follicular growth, estrus, and ovulation in swine. In many European countries, eCG is commercially available for inducing estrus in sows and gilts. The hormone is administered in doses ranging from 250 to 2000 IU but often shows mixed results for estrus and ovulation, which may depend on the preparation purity, dosage used, and even physiologic status of the animal. Use of even moderate to high doses of eCG (greater than 750 IU) has not consistently resulted in improvements. Another gonadotropin, hCG, also will induce ovulation, but it is relatively ineffective in initiating estrus. When administered alone (in a dose of 200–750 IU), however, hCG has been reported to induce estrus and ovulation in prepubertal gilts, but as with eCG, this response also appears highly variable.
A combination of eCG and hCG has proved to be even more effective than either hormone given alone. In studies that have compared the use eCG and hCG alone with the administration of the hormones simultaneously or the use of 500 IU of hCG at 48 to 96 hours after an injection of eCG, estrus expression, ovulation, and ovulation rate all are improved. The most efficient and effective dose appears to be 400 IU of eCG and 200 IU of hCG, although variation of the amount of eCG (300–1000 IU) and hCG (200–750 IU) in a single injection or given separately 48 to 72 hours apart has been reported to be effective. Despite this, little or no advantage is gained with use of higher doses of either hormone. In most instances, the low doses of eCG (less than 750 IU) induce low to normal ovulation rates (6 to 16 ova), and superovulation (greater than 20 ova) usually is induced only after a dose of 1000 IU or more. The use of these agents combined in a single injection (400 IU eCG and 200 IU hCG) was made possible by the development of PG600.* This combination hormone is approved worldwide for induction of puberty in gilts that have attained a weight of 185 pounds and an age of 5½ months. In most published reports, PG600 has been effective for inducing greater than 55% of gilts into estrus within 7 days of injection. The percentage of gilts ovulating is greater than 90%, and average ovulation rate, although variable, typically falls between 12 and 15 ovulations. When inducing puberty in gilts after 180 days of age and mating at the induced estrus or even at a fixed time after administration of PG600, 65% to 70% farrow, with no changes in litter size observed. When one cycle is skipped before breeding after PG600 estrus induction, however, both litter size and farrowing rate improve.22
Hormone products other than eCG (with or without hCG) are not as efficacious in inducing estrus and ovulation. Single injections of 250 μg of GnRH consistently fail to induce ovulation or estrus in gilts because the short release of FSH and LH apparently will not induce estrus or ovulation. Injections of GnRH in addition to eCG have not improved the response. Hourly administration of GnRH for several days is required to induce estrus and ovulation with this hormone alone. Combinations of porcine FSH and LH also have been reported to be effective for inducing estrus and ovulation, but their short half–lives (approximately 0.5 to 1 hour) relative to that of eCG (36 hours) dictates that they be administered in large doses and at multiple intervals. Induction of estrus in prepubertal gilts by estrogen administration (5–200 μg/kg) in single or even multiple injections over 2 to 3 days has resulted in both good and poor induction rates. In some instances, however, estrus without ovulation and low numbers of ovulations are observed. Exogenous estrogens such as estradiol benzoate (17β-estradiol-3-benzoate), and estradiol cypionate (estradiol-17β–cyclopentylpropionate) will consistently induce estrus and a preovulatory-like discharge of LH but will induce ovulations in only a few instances. When females are treated with hCG plus estradiol, both estrus and ovulation occur, but litter size is reported to be reduced. As indicated by the relative ineffectiveness of these alternative hormones in comparison with eCG and hCG, and the difficulty in administration, these methods become less than practical in commercial situations.