Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Para-n-benzene - sulfoxy-n containing doai – and said benzene...
Reexamination Certificate
2000-05-30
2003-06-03
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Para-n-benzene - sulfoxy-n containing doai, and said benzene...
C514S274000
Reexamination Certificate
active
06573254
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to method of enhancing gonadal development in an animal by administration of an agent which results in lowered levels of a thyroid hormone such as T
3
and elevation of plasma gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone (FSH)).
2. Related Art
Over the past few decades two environmental manipulations have been used in the poultry industry to regulate the onset of sexual maturation: photoperiod and nutrition. Pullets kept in total darkness or under short photoperiods display a delay in initial egg production (Wilson and Woodward,
Poultry Sci.
37:1054-1057 (1958); King,
Poultry Sci.
40:479-484 (1961)). In contrast, increasing day lengths have been shown to stimulate reproductive development in many avian species including domestic fowl (Farner and Follett,
J. Anim. Sci.
25:Suppl. 90-118 (1966); van Tienhoven and Planck, The effect of light on avian reproductive activity, Handbook of Physiology, Endocrinology II, Part 1, Chapter 4, pp. 79-107 1972). Chicks can be maintained at a physiological age of about 10 days for many months using protein-, amino acid-, or energy-deficient diets just sufficient to fill maintenance requirements (McCance,
Br. J. Nutr.
14:59-73 (1960); Dickerson and McCance,
Br. J. Nutr.
14:331-338 (1960)). Return to an unrestricted, nutritional diet restores growth and development to a normal rate with little subsequent effect on adult body size or egg production (McRoberts,
J. Nutr.
87:31-40 (1965)).
Continued manipulation of photoperiod and nutrition (particularly feed restriction) has been used in the broiler industry. The latter has become a necessary management tool due to a propensity for broiler-breeders to become obese. This is a consequence of the marked improvements in weight gain and feed conversion made by genetic selection and advances in the knowledge of dietary requirements. Unfortunately, rapid growth rate in broilers has resulted in obesity and decreased efficiency in the reproductive system of breeder stock (Reddy, Artificial insemination of broilers: economic and management implications. In:Proceedings of the First International Symposium on the Artificial Insemination of Poultry. The Poultry Science Assoc., Inc., Savoy, Ill., pp.73-89, 1994). Research has been completed comparing the reproductive performance of females between broiler breeder and egg-laying strains of domestic chickens (Dunn and Sharp,
J. Reprod. Fert.
90:329-335 (1990); Eitan and Soller,
Poultry Sci.
70:2017-2022 (1991);
Poultry Sci.
73:769-780 (1994);
Poultry Sci.
75:828-832 (1996); Robinson, Ovarian form and function in chickens of varying reproductive status. Final Report, Alberta Agricultural Research Institute Project # AAR1920202. Univ. Alberta, Edmonton, Canada (1994); Eitan et al.
Poultry Sci.
77:1593-1600 (1998)). Conclusions that have been reached from the cited studies are:
1. Female broilers compared to Leghorns are less responsive to photoperiodic manipulations with respect to optimal reproductive performance (Eitan and Soller,
Poultry Sci.
70:2017-2022 (1991);
Poultry Sci.
73:769-780 (1994); Eitan et. al.
Poultry Sci.
77:1593-1600 (1998));
2. Layer and broiler females differ in the minimal number of hours of light required to stimulate release of gonadotropins and initial development of their reproductive systems [critical day length, (CDL)] and the minimal number of hours of light above which no further increase in release of gonadotropins occurs [saturation day length, (SDL)] (Dunn and Sharp,
J. Reprod. Fert.
90:329-335 (1990); Eitan et al.
Poultry Sci.
77:1593-1600 (1998)); and,
3. Broiler breeder hens are less responsive to artificially increased photoperiodic manipulations compared to table egg layers under the effects of feed restriction (Robinson, Ovarian form and function in chickens of varying reproductive status. Final Report, Alberta Agricultural Research Institute Project # AAR1920202. Univ. Alberta, Edmonton, Canada (1994); Eitan et al.
Poultry Sci.
77:1593-1600 (1998)).
Eitan and Soller,
Poultry Sci.
75:828-832 (1996), compared the performance of male broiler breeders to that of male Leghorn or layer-type poultry under controlled photoperiod and/or dietary manipulations. They developed a maturation index for comparing different lines of birds.
There are clear indications that the reproductive system of broiler breeders has been compromised, particularly during the past decade (Beaumont, et al.
Br. Poult. Sci.
33:649-661 (1992); Reddy, Artificial insemination of broilers: economic and management implications. In:Proceedings of the First International Symposium on the Artificial Insemination of Poultry. The Poultry Science Assoc., Inc., Savoy, Ill., pp.73-89 (1994); Eitan and Soller,
Poultry Sci.
75:828-832 (1996); Goerzen et al.
Poultry Sci.
75:962-965 (1996)). Elite male broiler breeders have been shown to exhibit premature loss of adequate numbers of viable spermatozoa. It has been suggested that up to 80% of selected males in pure lines are lost due to significant decreases in semen production (Personal communication with primary breeder personnel in the broiler industry; unpublished data from over 200 male broiler breeders). This marked reduction of selection potential can dramatically reduce genetic progress that can be made within a given type of bird, reducing the future competitiveness of specific lines.
Sulfamethazine (SMZ) is an antibiotic developed by Merck in the late 1940s for treating fowl cholera (Kiser et al.
Poultry Sci.
27:257-262 (1948)) as well as other poultry diseases, such as coccidiosis. A side effect associated with chronic use of SMZ is a marked red coloration of the comb and increased size of both comb and testes (van Tienhoven et al.
Poultry Sci.
35:179-191 (1956)). Its mechanism of action in this regard is unknown. Further studies have been conducted with broiler chicks. The compound significantly increases testes development, transiently suppresses a thyroid hormone, increases plasma gonadotropins, appears to augment photoperiodic response, induces the hypothalamo-pituitary-gonadal axis, and increases the number of immuno-stained neuropeptide Y(NPY) neurons in the mediobasal hypothalamus and infundibular nucleus (IN) (Macko, Walsh and Kuenzel,
Brain Res. Bull.
44:707-713 (1997); Kuenzel, Macko, Walsh and Proudman, In Perspectives in Avian Endocrinology (Eds. S. Harvey and R. J. Etches), Journal Endocrinology Ltd., Bristol, pages 81-90 (1997). In addition, it has been shown that intracerebroventricular (ICV) administration of NPY to chicks stimulates growth of the testes (Fraley and Kuenzel,
Life Sci.
52:1649-1656 (1993)). In the rat, it has been shown that NPY neurons in the arcuate nucleus [the IN of the chick is equivalent to the arcuate n. (ARC) of mammals, (Kuenzel and van Tienhoven,
J. Comp. Neurol.
206:292-313 (1982)), appear to be involved in augmenting the LH surge in females (Kaira and Crowley,
Ann. N.Y. Acad. Sci.
611:273-283 (1984); Sar et al.
Endocrinology
127:2752-2756 (1990)).
SUMMARY OF THE INVENTION
The invention relates to a method for enhancing the development of viable sperm in a male animal and ovarian development in a female animal, comprising administering to said animal an effective amount of an agent which transiently lowers the levels of a thyroid hormone, specifically T
3
, e.g. by affecting its synthesis or metabolism, and which agent also increases gonadotropins. The most robust effect occurs in males. Normally, semen is not obtained from commercial poultry lines until 16-25 weeks of age. According to the present invention, semen production is produced by 9 weeks of age. Thus, the present invention represents a significant advance in the art.
The invention also relates to a method for synchronizing the onset of puberty in feed-restricted and light-restricted birds by administering to the birds the agent on or about the time that the photoperiod is increased (e.g. weeks 20 through 28 for broiler breed
Kirby John D.
Kuenzel Wayne J.
Sterne Kessler Goldstein & Fox P.L.L.C.
Travers Russell
University of Maryland
Wang Shengjum
LandOfFree
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