Hormonal induced lactation in transgenic goats

Abstract

The aim of this study was to hormonally induce lactation in prepubertal, nulliparous, and male goats both transgenic and non-transgenic. Analysis of milk quality, recombinant protein expression levels, total amount of recombinant protein produced, and the affect on long-term reproductive capability was assessed. Fifty-one goats (Saanen, Alpine, and Toggenburg), male and non-pregnant females, 2-31 months of age, either non-transgenic or transgenic were evaluated with a total of 10 transgenes (constructs) represented. Animals were given estradiol (0.25 mg/kg, i.m.) and progesterone (0.75 mg/kg, i.m.) on days 1, 3, 5, 7, 9, 11 and 13, while prednisilone (0.4 mg/kg, i.m.) was administered on days 14-16 with mammary massage occurring daily from day 5 onward. Forty of 51 animals, (36 of 38 females and 4 of 13 males) produced milk with total volumes in the 30-day experiment, ranging from 20 microl to 530 mls per day, or approximately 500 microl to 6.8 liters total. Milk composition was analyzed for various parameters (total protein, fat content, total solids and somatic cell count) with no significant differences found between induced and natural milk. Expression levels of recombinant proteins from transgenic animals that were analyzed during the induced lactation, and subsequently during normal lactations, were found to have no significant differences. Total amount of recombinant protein produced was evaluated at different expression levels with no statistical significance seen. While over 90% of the females placed in the regimen became pregnant, there was a correlation between increased age at time of induction and an increase in number of breedings, or reproductive cycles needed to establish a pregnancy after induction. For males, 100% placed in the regimen settled females after hormonal induction of lactation. Semen quality was evaluated prior to, during, and after hormonal treatments. Semen volume and sperm number did not differ; however, for a small percentage of males, there was a decrease in sperm and post thaw motility after hormonal treatments. These levels returned to normal within 4-5 weeks. Subsequent natural lactations showed total milk volumes within breed standards. These findings indicate that hormonal induction of lactation in the caprine species is a viable alternative to pregnancy for initiating lactation and milk production, does not adversely impact reproductive performance long-term, and can benefit the early assessment of recombinant proteins produced in a transgenic founder program.

Mammary Biopsy in Induced Lactating Goats: Assessment of Post-Biopsy Milk Properties and Ultrasonographic Appearance

“…The successful lactation rate of 100% verified in this study was similar to the results obtained in other induced trials (9) . Furthermore, the lactation initiated in a similar period that has alrady been cited for goats (3) . The values of average daily milk production obtained on the first thirty days of lactation were higher than those found by Batista et al (5) , who also studied milk hormonally induced Caninde goats in the same lactation period.…”

“…All does were hormonally induced to lactate using the protocol earlier described by Cammuso et al (3) . Briefly, estrogen (0.25 mg/kg, ECP, Pfizer, São Paulo, Brazil) and progesterone (0.75 mg/kg, Afisterone, Osasco, São Paulo, Brazil) were given on alternate days for a total of seven administrations.…”

“…The induction of lactation through hormonal stimulation has been previously demonstrated in goats (3)(4)(5) .…”

Transgenic mammalian species, generated by somatic cell cloning, in biomedicine, biopharmaceutical industry and human nutrition/dietetics - recent achievements

“…This latter possibility seems to result from the elevation of the milk yield of transgenic prepubertal does subjected to hormonal induction of lactation. Thereby, hormonally-enhanced propensity for the milk-mediated rhAT excretion appears to be affected by the reduction of the time necessary to obtain adequate quantities of this recombinant biopharmaceutical either for preclinical or clinical tests in humans (Cammuso et al 2000). The high expression profile of rhAT measured with its concentration or enzymatic activity (i.e., 5.8 g/l or 20.5 U/ml at Day 5, and 3.7 g/l or 14.6 U/ml at Day 9 of 33-day period of milking) detected in the milk of one nuclear-transferred goat, in which lactation had been prematurely induced at the age of two months for two weeks, indicates that onset of transcriptional activity for the integrated rhAT transgene copies may be accelerated significantly.…”

Genetically Engineered Animals and their Intended Uses in Day to Day Life

“…Another drug or blood protein which is under trial in Europe for FDA approval is 'Rhucin', a recombinant human C1 esterase inhibitor produced in the milk of transgenic rabbits. It can treat the acute attacks of hereditary angioedema (HAE), a rare disease characterized by painful swelling of soft tissue , polyclonal antibodies 10,11 , plasminogen activator [12][13][14][15] , human alpha-fetoprotein 16 , alpha-1-proteinase inhibitor, alpha glucosidase 5,9,17,18,19 etc C Vaccine components: Novel vaccine components are the products of genetically engineered animals helps in rapid manufacturing of vaccines. These vaccines can be produced comparatively in lower cost and even are effective in viral outbreaks such as pandemic flu [20][21][22] .…”