Changes in the reproductive function and developmental phenotypes in mice following intramuscular injection of an activin betaA-expressing plasmid.
BACKGROUND
The TGF-beta family protein activin has numerous reported activities with some uncertainty in the reproductive axis and development. The precise roles of activin in in vivo system were investigated using a transient gain of function model.


METHODS
To this end, an expression plasmid, pCMV-rAct, with the activin betaA cDNA fused to the cytomegalovirus promoter, was introduced into muscle of the female adult mice by direct injection.


RESULTS
Activin betaA mRNA was detected in the muscle by RT-PCR and subsequent Southern blot analysis. Activin betaA was also detected, and western blot analysis revealed a relatively high level of serum activin with correspondingly increased FSH. In the pCMV-rAct-injected female mice, estrus stage within the estrous cycle was extended. Moreover, increased numbers of corpora lutea and a thickened granulosa cell layer with a small antrum in tertiary follicles within the ovary were observed. When injected female mice were mated with males of proven fertility, a subset of embryos died in utero, and most of those that survived exhibited increased body weight.


CONCLUSIONS
Taken together, our data reveal that activin betaA can directly influence the estrous cycle, an integral part of the reproduction in female mice and activin betaA can also influence the embryo development as an endocrine fashion.
Kim
Mi-Nyeu
MN
Department of Life Science/Research Center for Biopharmaceutical Lead Molecule, The Catholic University of Korea, Bucheon, Korea. beautymn@hanmail.net
Park
Moon Nyeo
MN
Jung
Hoi Kyung
HK
Cho
Chunghee
C
Mayo
Kelly E
KE
Cho
Byung-Nam
BN
D028341:Activins / Q000097:blood; D000818:Animals; D015139:Blotting, Southern; D001835:Body Weight; D047108:Embryonic Development; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D028322:Inhibin-beta Subunits / Q000235:genetics*; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010053:Ovary / Q000166:cytology / Q000254:growth & development*; D010957:Plasmids / Q000008:administration & dosage; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology; D013997:Time Factors
D012333:RNA, Messenger; C103008:inhibin beta A subunit; D028341:Activins; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits