The role of IGFs in the regulation of ovarian follicular growth in the brushtail possum (Trichosurus vulpecula)

Abstract

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.

Key questions and answers about pregnancy-associated plasma protein-A

“…There are documented decreases in IGFBPs in human, bovine, equine, porcine, rodent, and possum follicles due to decreased IGFBP gene expression, as well as to increased PAPP-A [54-57]. IGF bioavailability through active intrafollicular IGFBP proteolysis involving PAPP-A has been shown to be an important determinant of follicular fate, i.e., development of healthy dominant versus atretic follicles [56,58-60].…”

Whole‐genome sequence analysis reveals candidate genomic footprints and genes associated with reproductive traits in Thoroughbred horse

“…The IGFBP2 and IGFBP5 genes were identified ( F ST , top 1%) in candidate selection regions on ECA6 that may have been influenced by directional selection (Table ). Insulin‐like growth factors (IGFs) play important role in the physiology of reproduction including, regulation of ovarian follicular development, implantation, maintenance of pregnancy and foetal growth (Gobikrushanth et al, ; Juengel et al, ; Monget et al, ). The IGF‐binding proteins, includes 6 distinct high‐affinity binding proteins (from IGFBP1 to IGFBP6), are a group of secreted proteins that bind IGFs I and 11, and are capable of modulating IGF actions on target cells (Bach, ; Juengel et al, ).…”

“…Insulin‐like growth factors (IGFs) play important role in the physiology of reproduction including, regulation of ovarian follicular development, implantation, maintenance of pregnancy and foetal growth (Gobikrushanth et al, ; Juengel et al, ; Monget et al, ). The IGF‐binding proteins, includes 6 distinct high‐affinity binding proteins (from IGFBP1 to IGFBP6), are a group of secreted proteins that bind IGFs I and 11, and are capable of modulating IGF actions on target cells (Bach, ; Juengel et al, ). IGFBP2, a key member of the IGF family, is present in follicular fluid and subject to dynamic changes during follicle growth and maturation (Spitschak & Hoeflich, ).…”

“…In assessing the genetic basis underlying the low reproductive efficiency of Thoroughbred, we identified several candidate genes that are associated with reproductive traits in horse and other species. The IGFBP2 and IGFBP5 genes were identified (F ST , top 1%) in candidate selection regions on ECA6 that may have been influenced by directional selection (Table 1) target cells (Bach, 2018;Juengel et al, 2010). IGFBP2, a key member of the IGF family, is present in follicular fluid and subject to dynamic changes during follicle growth and maturation (Spitschak & Hoeflich, 2018).…”

PAPP-A: a promising therapeutic target for healthy longevity

“…It was characterized as a metalloproteinase of the metzincin superfamily and defined a new subfamily, the pappalysins, distinct from previously recognized subfamilies including the matrix metalloproteinases (Boldt et al ., ). Since the discovery of its function, PAPP‐A and its proteolytic activity have been studied in a diverse range of species, including human, baboon, cow, pig, mouse, naked mole rat, marsupial, and zebrafish (Mazerbourg et al ., ; Conover et al ., ; Tchoukalova et al ., ; Juengel et al ., ; Phang et al ., ; Kjaer‐Sorensen et al ., ; Brohus et al ., ). Based on genomic data, a gene encoding PAPP‐A appears to be present in all vertebrates.…”