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Failure of Gonadotropin Therapy to Induce Estrus in Gilts Treated with a Gnrh Analog to Suppress Ovarian Activity

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Failure of Gonadotropin Therapy to Induce Estrus in Gilts Treated with a Gnrh Analog to Suppress Ovarian Activity Failure of Gonadotropin Therapy to Induce Estrus in Gilts Treated with a GnRH Analog to Suppress Ovarian Activity Antonio Garcia, DVM, PhD (deceased)a Mark J. Estienne, PhDb Allen F. Harper, PhDb James W. Knight, PhDb aDepartment of Large Animal Clinical Sciences Virginia-Maryland Regional College of Veterinary Medicine Blacksburg, VA 24061 bDepartment of Animal and Poultry Science Virginia Polytechnic Institute and State University Blacksburg, VA 24061 KEY WORDS: gilts, GnRH, gonadotropin, mm follicles 4 days after implant insertion ovarian activity was significantly (P < .05) higher in con- trols than in gilts receiving a deslorelin ABSTRACT implant. The percentage of deslorelin- A study was conducted to determine implanted gilts that displayed a normal whether treatment with deslorelin, a estrous cycle was significantly (P < .05) gonadotropin-releasing hormone (GnRH) lower than in individuals given a sham analog, produced anestrus in gilts and to test implant. There was no significant difference the ability of exogenous gonadotropin treat- in the percentage of implanted-gilts that dis- ment with a combination of 400 IU equine played estrus within 10 days after injection chorionic gonadotropin and 200 IU human of either 400 IU equine chorionic gonadotropin chorionic gonadotropin to induce estrus in and 200 IU human chorionic gonadotropin GnRH analog-treated gilts. Twelve days or deionized water. Treatment with a prod- after the third estrus, 11 gilts each received uct containing a combination of 400 IU a full SC implant containing 2.1 mg deslore- equine chorionic gonadotropin and 200 IU lin, a half implant containing 1.05 mg human chorionic gonadotropin failed to deslorelin, or a sham implant. The implants induce estrus in gilts caused to be in anestrus remained in place for the duration of the by implanting the GnRH analog deslorelin. study. Approximately 23 days after place- ment of implants, GnRH analog-treated gilts INTRODUCTION that had not returned to estrus (n = 18) Gonadotropin-releasing hormone (GnRH) is received IM injections of either 400 IU secreted by the hypophysiotropic neurons of equine chorionic gonadotropin and 200 IU the hypothalamus. The decapeptide induces human chorionic gonadotropin or deionized synthesis and secretion of luteinizing hormone water. The percentage of gilts with 3- to 4- (LH) and follicle-stimulating hormone (FSH) Intern J Appl Res Vet Med • Vol. 2, No. 3, 2004 195 from gonadotropes located in the anterior pitu- by the Institutional Animal Care Committee. itary gland.1 Since the initial discovery of Prepubertal Yorkshire × Landrace gilts (n = GnRH as the hypothalamic factor controlling 42) approximately 180 days of age were gonadotropin release, numerous GnRH ago- given an IM injection of P.G. 600 containing nists and analogs have been developed and 400 IU equine chorionic gonadotropin (eCG) studied for their pro-fertility potential.2,3 and 200 IU human chorionic gonadotropin Paradoxically, suppressive effects of (hCG). Gilts were checked for estrus once potent GnRH analogs on reproduction have daily beginning at the time of P.G. 600 been reported. For example, chronic treat- administration. Estrus was defined as the ment of cows with a GnRH analog resulted period during which gilts displayed a lordo- in an initial stimulation of gonadotropin sis response in the presence of a mature release, which was soon followed by sup- boar. Within 7 days after the injection (4.3 ± pressed secretion, and ultimately, inhibition 0.1 days), 83% (35/42) of the gilts displayed of ovarian follicular development.4 The estrus. Of these 35, 97.1% subsequently dis- mechanism by which GnRH analogs cause played a second estrus and 94.3% a third reduced gonadotropin secretion and abated estrus at approximately 21-day intervals. ovarian function presumably involves a Gilts that had displayed three periods of desensitization or down regulation of GnRH estrus (i.e., two estrous cycles) were selected receptors on the anterior pituitary gland. to participate in the study. Miller et al5 reported that treatment of On Day 12 after the third estrus, 11 gilts gilts during the luteal phase of the estrous each received in the base of an ear a full SC cycle with a potent GnRH agonist caused implant containing 2.1 mg deslorelin, a half suppression of ovarian activity that was implant containing 1.05 mg deslorelin, or a reversed 28 days later by exogenous a sham implant. The deslorelin implants gonadotropin administration. Reproductive remained in place for the duration of the efficiency in swine breeding herds could be study. Gilts returning to estrus between Days 19 and 22 of the third estrous cycle enhanced by effective methods of synchro- were considered to have had a cycle of nor- nizing estrus in replacement gilts. In theory, mal duration. gilts could be treated with a GnRH analog Approximately 23 days after insertion of to cause a state of anestrus and then syn- implants (Day 35.4 ± 0.5), deslorin-treated chronized estrus could be induced by gilts that had not returned to estrus (n = 18) administration of gonadotropin. The objec- received IM injections of either P.G. 600 (n tives of this study were to determine = 9) or deionized water (n = 9). Of the nine whether a GnRH analog would produce a gilts that had received the full deslorelin state of anestrus in gilts and to test the abili- implant, four were injected with P.G. 600 ty of exogenous gonadotropin treatment to and five received deionized water. Of the induce estrus in GnRH analog-treated gilts. nine gilts that had received the half implant, Commercially available GnRH analog five were injected with P.G. 600 and four (Ovuplant; Fort Dodge Animal Health) and received deionized water. gonadotropin (P.G. 600; Intervet America) Ultrasonography products were employed. Transrectal ultrasonography of the ovaries MATERIALS AND METHODS was performed 4 days after implant insertion using a real-time, B-mode ultrasound Preparation of Subjects machine (Aloka SSD-500; Aloka) equipped The study was conducted at the Virginia with a linear-array 5-MHz transducer Tech-Tidewater Agricultural Research and designed for intrarectal placement. The gilts Extension Center in Suffolk, VA, and the were restrained in standing position inside a study protocol was reviewed and approved portable scale. The ultrasound transducer was 196 Vol. 2, No. 3, 2004 • Intern J Appl Res Vet Med modified by taping a half-moon polyvinyl lower than for sham-implanted individuals chloride pipe along the dorsal part of the (Table 1). There was no significant effect of probe to control manipulation of the transduc- treatment (P > .05) on the interestrus inter- er in the rectum. The modified transducer was val for gilts displaying estrus after implant well lubricated with corn oil before insertion insertion (Table 1). into the rectum and was gently passed along There were no significant (P > .05) dif- the rectal floor to avoid fecal material resist- ferences between groups in the concentra- ance and to establish good contact between tions of progesterone at implant insertion on the transducer and the rectal mucosa. Day 12 or at Day 16 of the estrous cycle. In Blood Samples and Radioimmunoassay deslorin-treated gilts, concentrations of prog- Beginning at implant insertion and continu- esterone in serum remained low until the ing until estrus or injection of either P.G. time of P.G. 600 or deionized water adminis- 600 or deionized water, blood samples were tration at approximately Day 35 (Table 1). collected via jugular venipuncture at 4-day There was no significant (P > .05) difference intervals. Samples were allowed to clot in the percentage of implanted-gilts that dis- overnight at 4˚C. Serum was harvested fol- played estrus within 10 days after injection of lowing centrifugation and stored at –20˚C either P.G. 600 or deionized water (Table 2). until assayed. Serum progesterone concen- trations were determined using a validated DISCUSSION radioimmunoassay method described for Implants containing the potent GnRH ana- swine by Tarraf and Knight.6 The intraassay log deslorelin were successful at producing and interassay coefficients of variation were anestrus in gilts by inhibiting follicular 4.6% and 8.9%, respectively. Assay sensitiv- growth. Four days after insertion of implants ity was 0.02 ng/mL serum. containing either 1.05 or 2.1 mg deslorelin, suppressed follicular development was Statistical Analysis observed ultrasonographically. The lack of The interestrus interval was defined as the estrous cyclicity was confirmed by the period between the onset of two subsequent observation of low progesterone concentra- periods of standing estrus. The percentage tions in serum for an extended period after of gilts displaying estrus after treatment and implant insertion. The mechanism mediating the percentage of gilts with 3- to 4-mm fol- this prolonged anestrus probably involved licles 4 days after treatment (Day 16 of suppression of gonadotropin secretion and estrous cycle) were compared using chi- ultimately an inhibition of follicular devel- square analysis. The interestrus interval and opment. Although serum concentrations of serum progesterone concentrations were gonadotropins were not determined in this analyzed by analysis of variance using the study, previous work from the authors’ labo- GLM procedure of SAS (SAS Institute). ratory demonstrated that treatment of male swine with deslorelin implants decreased RESULTS secretion of LH, testosterone, and estradiol.7 Insertion of implants containing the GnRH Treatment with the GnRH analog analog deslorin at Day 12 of the estrous deslorelin caused a desensitization of the cycle resulted in suppression of follicular female bovine pituitary gland to GnRH.8 growth. The percentage of gilts with 3- to 4- Treatment with deslorelin for 3 days result- mm follicles 4 days after implant insertion ed in a prolonged period of anestrus in post- was significantly (P < .05) higher in con- partum dairy cows implanted within 3 days trols than in gilts receiving a full or half of calving.9 As postulated in cattle, the implant (Table 1).
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