Follicle-Restricted Compartmentalization of Transforming Growth Factor β Superfamily Ligands in the Feline Ovary1

• Published in: Biology of reproduction Vol. 70; no. 3; pp. 846 - 859
• Main Authors: Bristol, Sarah K, Woodruff, Teresa K
• Format: Journal Article
• Language: English
• Published: 01-03-2004
• Subjects: activin; Contents; follicle; granulosa cells; inhibin; ovary
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.021857

Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor β (TGFβ) superfamily. TGFβ, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFβ superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin α subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin βA and βB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin βA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFβ1, 2, and 3 ligand immunoreactivity is observed in both small and large follicles, whereas the TGFβ type II receptor (TGFβ RII) is detected in the oocyte and granulosa cells of antral follicles. The intracellular signaling proteins Smad2 and Smad4 are present in the granulosa cell cytoplasm of all follicle size classes. Smad3 is detected in the granulosa cell nucleus, the oocyte, and the theca cell nucleus of all follicle size classes. These data suggest that the complete activin signal transduction pathway is present in small follicles and that large follicles primarily produce the inhibins. Our data also suggest that TGFβ ligands and receptors are colocalized to large antral follicles. Taken together, the ligands, receptors, and signaling proteins for the TGFβ superfamily are present at distinct points throughout feline folliculogenesis, suggesting discrete roles for each of these ligands during follicle maturation.