Use of Zeranol to modulate reproductive cycles

#This invention relates to a method for modulating the function of the female reproductive system in animals, especially farm animals, and specifically in pigs and horses, by administering an effective amount of zeranol. Specifically, this invention provides a method for inducing pseudopregnancy, maintaining pregnancy, and maintaining progesterone synthesis and/or secretion from the corpus luteum, especially in pigs and horses, by administering an effective amount of zeranol.

#The control of estrus cycle synchronization in animals is desirable for many reasons. The timing of fertility and mating in animals is influenced by many factors, such as puberty onset, seasonal conditions, diet, photoperiod, heat, stress, crowding, transportation, lactation, recovery from previous pregnancy, recovery from lactation, and a variety of hormonal, neuroendocrine and immunological factors. In farm animals, the ability to control the estrus cycle directly affects the efficiency of animal husbandry and the cost of animal products. Some domesticated animals, such as horses, are raised for racing and other competitive events. Race horses enter the racing season based on age. Animals born early in a year will be stronger and larger than horses born later in the season. What is needed is a method to control the estrous cycle in horses so that the timing of fertility may be selected.

#At present, no approved product or procedure exists for efficient and precise estrus synchronization in swine within the United States. In Europe, feeding of an oral progestin sold under the trademark REGU-MATE (Roussell UCLAF, France), is approved for estrus synchronization in mature cycling pigs. The oral progestin simulates the presence of functional corpora lutea (CL) as if the pig were pregnant. REGU-MATE must be supplied daily in the feed for about two weeks to achieve estrus synchronization. REGU-MATE is also quite expensive at a cost of about $2 per day per animal. Removal of REGU-MATE following 11 to 14 days of feeding results in the resumption of synchronous estrus cycles. REGU-MATE is not currently approved for use in the United States.

#FIG. 1 shows a synchronization protocol for prepubertal and peripubertal gilts. 500 IU of hCG can be administered as early as 4 months of age to induce ovulation. Alternatively, PG600 can be used to induce ovulation in older gilts (i.e., 5-8 months of age). Whether administered orally or as an implant, zeranol should be administered so that it will be present during the period of maternal recognition of pregnancy, days 11-15 of the induced estrous cycle, in order to induce pseudopregnancy. Zeranol-induced pseudopregnancy is later terminated with PG. About 85%-90% of gilts will display estrus within 3-7 days following treatment with PG.

#FIG. 2 shows a synchronization protocol for cycling gilts and sows. Whether administered orally or as an implant, zeranol should be administered so that it will be present during the period of maternal recognition of pregnancy, days 11-15 of the estrous cycle, in order to induce pseudopregnancy. Zeranol-induced pseudopregnancy is later terminated with PG. Gilts and sows will display estrus within 3-7 days following treatment with PG.

#FIG. 3 displays a synchronization protocol for lactating sows. hCG or a combination of PMSG/hCG is injected at farrowing to induce ovulation. Whether administered orally or as an implant, zeranol should be administered so that it will be present during the period of maternal recognition of pregnancy, days 11-15 of the estrous cycle, in order to induce pseudopregnancy. Zeranol-induced pseudopregnancy is later terminated with PG. Sows display estrus within 3-7 days after treatment with PG.

#The term "zeranol" is synonymous with zearanol, .alpha.-zearalanol, zearalanol, RALGRO, P-1496, 3,4,5,6,7,8,9,10,11,12-Decahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxac yclotetradecin-1-one; (3S,7R)-3,4,5,6,7,8,9,10,11,12-decahydro-7,14,16-trihydroxy-3-methyl-1H-2- benzoxacyclotetradecin-1-one; 6-(6,10-dihydroxyundecyl)-beta-resorcylic acid, mu-lactone; frideron; MK-188; ralabol; ralone; [3S-(3R*,7S*)]-3,4,5,6,7,8,9,10,11,12-decahydro-7,14,16-trihydroxy-3-methy l-1H-2-benzoxacyclotetradecin-1-one; (3S,7R)-(+)-3,4,5,6,7,8,9,10,11,12-decahydro-7,14,16-trihydroxy-3-methyl-1 H-2-benzoxacyclotetradecin-1-one; including derivatives and analogs thereof.

#The term "zearalenone" is synonymous with benzoxacyclotetradecin-1,7(8H)-dione; compound F-2; FES; (-)-zearalenone; trans-zearalenone; 6-(10-hydroxy-6-oxo-trans-1-undecenyl)-beta-resorcylic acid lactone; fermentation estrogenic substance; f-2 toxin, fusarium toxin; mycotoxin f2; ntoxin f2; (S)-Zearalenone; (10S)-zearalenone.

#The term "pseudopregnancy" means a state of false pregnancy in which the function of the uterine endometrium resembles that of the pregnant uterus. In pseudopregnancy, the progesterone secretory function of the corpora lutea is maintained, thereby holding in abeyance the onset of the next estrus.