The role of Notch signaling in the mammalian ovary

Abstract

The Notch pathway is a contact-dependent, or juxtacrine, signaling system that is conserved in metazoan organisms and is important in many developmental processes. Recent investigations have demonstrated that the Notch pathway is active in both the embryonic and postnatal ovary and plays important roles in events including follicle assembly and growth, meiotic maturation, ovarian vasculogenesis, and steroid hormone production. Ovarian pathologies resulting from disruption of the Notch pathway in mice affect meiotic spindle assembly, follicle histogenesis, granulosa cell proliferation and survival, corpora luteal function, and ovarian neovascularization. These aberrations result in abnormal folliculogenesis and reduced fertility. Knowledge of the cellular interactions facilitated by the Notch pathway is an important area for continuing research and future studies are expected to enhance our understanding of ovarian function and provide critical insights for improving reproductive health. This review focuses on the expression of Notch pathway components in the ovary, and on the multiple functions of Notch signaling in follicle assembly, maturation, and development. We focus on the mouse, where genetic investigations are possible, and relate this information to the human ovary.

Transcriptomic Analysis for Differentially Expressed Genes in Ovarian Follicle Activation in the Zebrafish

“…In addition to gonadotropins and steroids, a large number of local ovarian paracrine factors especially peptide growth factors have been reported to play roles in controlling mammalian folliculogenesis especially during early stages ( 76 , 85 ), including families of IGF ( 86 ), EGF ( 87 ), TGF-β ( 88 ), activin ( 89 ), BMP including BMP15 and GDF9 ( 90 ), Kit ( 91 ), and Notch ( 92 ). These growth factors and their signaling components also exist in the zebrafish ovary ( 22 , 24 – 27 , 30 , 34 , 93 , 94 ).…”

Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology

“…The NOTCH system (ligands, receptors, and target genes) is expressed in the ovaries in different structures, such as oocytes, primary, secondary and antral follicles, corpora lutea, theca cells, ovarian surface epithelium, and vasculature (Vanorny & Mayo, and references therein). Various critical roles have been defined for NOTCH factors in ovary biology, such as follicle formation and growth, meiotic maturation, vasculogenesis, and hormone synthesis (George, Hahn, Rawls, Viger, & Wilson‐Rawls, ; Trombly, Woodruff, & Mayo, ; Vanorny & Mayo, ; Xu & Gridley, ). These findings support proposing NOTCH2 as a coherent candidate gene related to POI's etiology.…”

“…Notch2 is expressed in pregranulosa cells during ovary development in mice and participates in resolving germ cell syncytia and primordial follicle formation (Vanorny, Prasasya, Chalpe, Kilen, & Mayo, ). Although the constitutive Notch2 knock‐out (KO) model ( Notch −/− ) has displayed embryonic lethality, its conditional deletion in granulosa cells has led to a decreased number of primordial follicles, disorganized follicle growth and abnormal folliculogenesis (Vanorny & Mayo, ; Vanorny et al., ; Xu & Gridley, ). NOTCH family members (including NOTCH2) are also expressed during follicular growth in humans and reduced NOTCH2 expression in cumulus granulosa cells has been found in poor responders during in vitro fertilization treatment (Kristensen, Ebbesen, & Andersen, ; Tanriverdi et al., ).…”

Epidermodysplasia Verruciformis: Functional Role of E6 and E7 Oncoproteins as the Link between Viral Infection to Carcinogenesis

“…Notch pathway is a signalling system which is categorized as a contact dependent pathway. 44 It gets activated by a cell to cell contact process where the ligands that are anchored to the membrane and belong to the Jagged or the Delta family, bind to the Notch receptors. 43 It is involved in the embryogenesis and in the developmental process of organism.…”