Activin, Inhibin, and Follistatin in Zebrafish Ovary: Expression and Role in Oocyte Maturation1

Abstract

Activins, inhibins, and follistatins are important regulators of mammalian reproduction. However, their roles in lower vertebrates are poorly understood. In this study, we examined the expression of activin A, inhibin A, and follistatins in the zebrafish ovary and determined their role in final oocyte maturation. Using reverse transcription-polymerase chain reaction with primers specific for activin/inhibin beta(A) subunit and for follistatins, we detected DNA fragments of the expected size, which, upon sequencing, conformed to activin/inhibin beta(A) and follistatin. Western blot analysis using an antibody against activin/inhibin beta(A) subunit revealed two bands with sizes similar to those of activin A and inhibin A. The expression of follistatins was also confirmed by Western blot analysis. These results suggest that activin A, an inhibin A-like molecule, and follistatins are expressed in the zebrafish ovary. In cultured zebrafish follicles, activin A and inhibin A both induced final oocyte maturation in a dose-dependent manner. The effects of activin A and inhibin A were blocked by their binding protein, follistatin-288. Interestingly, follistatin-288 also inhibited final oocyte maturation induced by gonadotropin and by maturation-inducing hormone (MIH), suggesting that activin A and/or inhibin A may be local regulators mediating gonadotropin- and MIH-induced final oocyte maturation. Taken together, these findings suggest that activin A and inhibin A are paracrine regulators of ovarian functions in fish.

Characterization of inhibin α subunit (inha) in the zebrafish: evidence for a potential feedback loop between the pituitary and ovary

“…In 1992, we first reported a stimulatory effect of porcine inhibin on the secretion of goldfish LH (GTH-II) in vitro (Ge et al 1992). A recent study in the zebrafish showed that human inhibin could stimulate final oocyte maturation in vitro, similar to the effect of activin (Wu et al 2000). In contrast, porcine inhibin suppressed oocyte maturation in the killifish, which was opposite to the effect of activin (Petrino et al 2007).…”

Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

“…Oocytes in the vitellogenenic stage experience an increase in size due to receptor-mediated endocytosis of vitellogenin, the precursor of the egg-yolk protein (Wang, Yan, Tan, & Gong, 2000). Early vitellogenic follicles are considered to be maturationally incompetent, as they are unable to respond to progestin hormones (see below), which function as maturational hormones (Wu et al, 2000). Mature oocytes undergo maturation, where the oocyte is released from prophase 1 and meiosis is resumed.…”

Maturation of Nile-Tilapia (Oreochromis niloticus) Oocytes With Exposed by Goat Inhibin Isolated from Granulose Cells

“…Bahan yang sering digunakan untuk manipulasi hormon antara lain adalah ekstrak pituitari atau gonadotropin murni, LHRH murni atau dikombinasi dengan dopamin, dan steroid (Rottmann et al, 1991). Selain hormon di atas, faktor lain yang diketahui ikut merangsang terjadinya pematangan telur ikan antara lain activin, inhibin, dan follistatin (Wu et al, 2000), insulin-like growth factor (IGF-1) (Reinecke et al, 1997), epithelial growth factor (EGF), dan transformation growth factor (TGFα) (Wang dan Ge, 2002).…”

“…Menurut Krassel et al (2003), keberadaan molekul inhibin dalam darah mamalia berfungsi untuk menghambat sekresi FSH dan LH sehingga tidak terjadi superovulasi, tetapi hasil penelitian Wu et al (2000) menyimpulkan bahwa secara in vitro inhibin dapat mematurasi oosit pada ikan zebra (Danio rerio). Katsu et al (1993) mengemukakan ekspresi mRNA inhibin pada ikan salmon berbeda dengan ekspresi mRNA inhibin pada mamalia, sehingga diduga inhibin adalah salah faktor yang berperan mematangkan telur ikan.…”

“…Dalam proses reproduksi inhibin bersama aktivin diketahui meregulasi pelepasan GnRH dari hipotalamus dan FSH dari pituitari (Calogero et al, 1998). Secara spesifik, activin dan inhibin dalam sistim reproduksi berperan pada steroidogenesis, proliferasi spermatogonia, proliferasi sel granulosa, modulasi FSH, pertumbuhan folikel, dan maturasi (Wu et al, 2000). Hampir semua studi menyatakan aktivitas activin bertentangan dengan inhibin dalam proses biologi reproduksi.…”