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Changes in the reproductive function and developmental phenotypes in mice following intramuscular injection of an
Mi-Nyeu Kim1, Moon Nyeo Park, Hoi Kyung Jung
1Department of Life Science/Research Center for Biopharmaceutical Lead Molecule, The Catholic University of Korea, Bucheon, Korea. beautymn@hanmail.net
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.
Conclusion:
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.
Insights
Activin betaA influences female reproduction by extending the estrous cycle and enhancing embryo development. This study clarifies activin
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular biology
Background:
- The TGF-beta family protein activin has diverse roles in reproduction and development, but its in vivo functions remain incompletely understood.
- Previous research indicates potential involvement of activin in the reproductive axis, necessitating further in vivo investigation.
Purpose of the Study:
- To elucidate the precise in vivo roles of activin betaA in the female reproductive system.
- To investigate the effects of transient gain of function of activin betaA on the estrous cycle and early embryo development.
Main Methods:
- A transient gain of function model was established by introducing an expression plasmid (pCMV-rAct) encoding activin betaA into the muscle of adult female mice.
- Gene expression and protein levels of activin betaA were confirmed using RT-PCR, Southern blot, and Western blot analyses.
- Physiological and developmental effects were assessed by monitoring the estrous cycle, ovarian morphology, and subsequent embryo development after mating.
Main Results:
- Activin betaA expression was successfully induced in muscle tissue.
- Increased serum activin levels correlated with elevated Follicle-Stimulating Hormone (FSH) and an extended estrus stage.
- Ovarian analysis revealed increased corpora lutea, thickened granulosa cells, and altered tertiary follicle development. Embryos from treated mice showed increased birth weight, though some in utero mortality was observed.
Conclusions:
- Activin betaA directly impacts the estrous cycle, a critical component of female reproduction.
- Activin betaA exerts endocrine effects that influence embryonic development, potentially affecting offspring growth.
