Follistatin regulates germ cell nest breakdown and primordial follicle formation.

TitleFollistatin regulates germ cell nest breakdown and primordial follicle formation.
Publication TypeJournal Article
Year of Publication2011
AuthorsKimura F, Bonomi LM, Schneyer AL
JournalEndocrinology
Volume152
Issue2
Pagination697-706
Date Published2011 Feb
ISSN1945-7170
KeywordsAnimals, Animals, Newborn, Cell Proliferation, Female, Fluorescent Antibody Technique, Follistatin, Germ Cells, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Ovarian Follicle, Protein Isoforms
Abstract

Follistatin (FST) is an antagonist of activin and related TGFβ superfamily members that has important reproductive actions as well as critical regulatory functions in other tissues and systems. FST is produced as three protein isoforms that differ in their biochemical properties and in their localization within the body. We created FST288-only mice that only express the short FST288 isoform and previously reported that females are subfertile, but have an excess of primordial follicles on postnatal day (PND) 8.5 that undergo accelerated demise in adults. We have now examined germ cell nest breakdown and primordial follicle formation in the critical PND 0.5-8.5 period to test the hypothesis that the excess primordial follicles derive from increased proliferation and decreased apoptosis during germ cell nest breakdown. Using double immunofluorescence microscopy we found that there is virtually no germ cell proliferation after birth in wild-type or FST288-only females. However, the entire process of germ cell nest breakdown was extended in time (through at least PND 8.5) and apoptosis was significantly reduced in FST288-only females. In addition, FST288-only females are born with more germ cells within the nests. Thus, the excess primordial follicles in FST288-only mice derive from a greater number of germ cells at birth as well as a reduced rate of apoptosis during nest breakdown. These results also demonstrate that FST is critical for normal regulation of germ cell nest breakdown and that loss of the FST303 and/or FST315 isoforms leads to excess primordial follicles with accelerated demise, resulting in premature cessation of ovarian function.

DOI10.1210/en.2010-0950
Alternate JournalEndocrinology
PubMed ID21106872