Hormonal induced lactation in transgenic goats.
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.
Cammuso
C
C
Genzyme Transgenics Corporation, Framingham, MA 01702, USA.
Porter
C
C
Nims
S
S
Gaucher
D
D
Melican
D
D
Bombard
S
S
Hawkins
N
N
O'Coin
A
A
Ricci
C
C
Brayman
C
C
Buzzell
N
N
Ziomek
C
C
Gavin
W
W
D000818:Animals; D030801:Animals, Genetically Modified; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006041:Goats / Q000235:genetics / Q000502:physiology*; D007774:Lactation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors
D011994:Recombinant Proteins; D011374:Progesterone; D004958:Estradiol; C007630:estradiol 17 beta-cypionate; D011239:Prednisolone