Effects of Plasmid Growth Hormone–Releasing Hormone Treatment during Heat Stress

Abstract

A gene therapy treatment with plasmid-based growth hormone-releasing hormone (GHRH) delivered by electroporation (EP) was investigated during heat stress; 32 primiparous cows received 2.5 mg of a GHRH-expressing myogenic plasmid (pSP-HV-GHRH), while 20 were designated as controls. Offspring of treated animals showed a reduction in mortality (47%; p < 0.02), and survival from birth to 260 days was dramatically improved (0% mortality vs. 21% in controls) along with an increase in weight gain (p < 0.05). Milk production was increased compared to controls with an average yield gain of 421 kg/cow (p = 0.028). Prolactin (PRL) levels were also significantly increased compared to controls (p < 0.05). The second pregnancy rate was improved by GHRH treatment (53.3% vs. 30.8%). This study shows that the use of plasmid-mediated therapy delivered by EP can maintain health status during periods of heat stress, important for both animals and potentially humans in hot, challenging climates.

Growth Hormone–releasing Hormone Plasmid Treatment by Electroporation Decreases Offspring Mortality Over Three Pregnancies

“…7 Also, the better metabolic and health status of the treated sows, as well as improvements in immune responses, 30 may affect reproductive capacity and survival of the offspring. This last finding was described also in plasmid GHRH-treated cows, 26 and is currently addressed in a follow-up study. Regardless, the ability to increase the general well-being in sows, as well as to improve survival and health of offspring, combined with improvements in body composition parameters, are of great value.…”

“…The underlying mechanism by which the long-term effect was observed seems to be multifaceted and has been previously described in our pilot studies: metabolic changes in the mother with better nutrient utilization and higher lactation potential impact both growth pattern and survival of offspring from birth to weaning; 26,29 changes in pituitary lineage in the offspring of treated animals impact the stage of maturation at birth and postnatal growth and development. 7 Also, the better metabolic and health status of the treated sows, as well as improvements in immune responses, 30 may affect reproductive capacity and survival of the offspring.…”

“…25 We have previously shown that EP of GHRH-plasmid results in the improved well-being of horses with laminitis, 12 and cattle treated with GHRH followed by EP during periods of heat stress had reduced calf mortality, increased milk production and weight gain. 26 Previously, we have shown that the GHRH plasmid-mediated treatment of pregnant rats or pigs in the third part of their gestation results in increased pituitary somatotroph and lactotroph numbers, as well as postnatal growth rate of the offspring. 6,7 In rats, this was shown to be at least partially due to the hormone crossing the placenta and directly influencing fetal development.…”

“…19 The use of recombinant somatotropin has also been investigated. One study showed that the daily injection of somatotropin during early gestation (days [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] selectively improved the growth conditions for low-birth weight littermates. 20 Another study demonstrated that the daily treatment of sows in gestation with porcine somatotropin for 75 days increased offspring size at birth.…”

Effects of administration of two growth hormone–releasing hormone plasmids to gilts on sow and litter performance for the subsequent three gestations

“…Studies conducted over the past 2 decades have indicated that gene therapy is a viable alternative to traditional pharmaceutical or biological treatment in food and companion animals. Studies [3][4][5][6] have revealed that administration of GHRH plasmid via IM injection and electroporation and subsequent increases in downstream IGF-I concentrations are associated with improved maternal lactation, increased survival rate of offspring, and a higher rate of success for a second pregnancy. In early 2008, the Australian Pesticides and Veterinary Medicines Authority approved a plasmid for commercial use in pregnant swine, the first GHRH DNA treatment approved for use in food animals.…”