Date Published: March 02, 2018
Publisher: Impact Journals
Author(s): Yu-Lan Chu, Ya-Ru Xu, Wan-Xi Yang, Yi Sun.
Most of the mammalian follicles undergo a degenerative process called “follicle atresia”. Apoptosis of granulosa cells is the main characteristic of follicle atresia. Follicle stimulating hormone (FSH) and the transforming growth factor β (TGF-β) superfamily have important regulatory functions in this process. FSH activates protein kinase A and cooperating with insulin receptor substrates, it promotes the PI3K/Akt pathway which weakens apoptosis. Both Smad or non-Smad signaling of the transforming growth factor β superfamily seem to be related to follicle atresia, and the effect of several important family members on follicle atresia is concluded in this article. FSH and TGF-β are likely to mutually influence each other and what we have already known about the possible underlying molecular mechanism is also discussed below.
Folliculogenesis is a process describing the fate of oocytes and their surrounding somatic cells. Follicular development begins with the formation of primordial follicles which contain arrested primary oocytes and a layer of flat granulosa cells. Primordial follicles will be recruited into the growing follicle pool and proceed to further stages of development. Granulosa cells become cuboidal when primordial follicles mature into primary follicles and they turn into multilayers when they enter the stage of secondary follicles . Upon the formation of secondary follicles, outer granulosa cell layers differentiate into theca cells which encircle the inner granulosa layer and produce androgens for subsequent estradiol biosynthesis . When intervals between granulosa cells become larger and merge together to form an antral, follicles get the name of “antral” follicle. The granulosa cells can be further divided into cumulus cells and mural cells. The wall of antral follicles is lined with mural cells while oocytes are linked to the wall by cumulus cells [1,3]. Only very few follicles, in mammalian less than 1%, will be selected and finally ovulate as mature follicles, while others will undergo a process called follicle atresia, which means degeneration of the follicles.
Follicle atresia has important physiological functions in the female mammal reproductive system. It is based on cell apoptosis and is influenced by multiple factors in the ovary. FSH may be the most critical pro-survival factor for follicles. It functions through integrated signaling pathways where PKA is the major transducer. The crosstalk between different pathways is common and complex, and to follicle survival, interaction between PKA mad PI3K pathways is likely indispensable. Among various intra-ovarian paracrine and autocrine factors, the TGF-β superfamily is best studied in terms of its effect on follicle atresia. The cooperation and mural effects of FSH and TGF indicate the delicate management of the follicles. Elucidation of the molecular mechanism underneath follicle atresia may provide new insights into disorders related to intensified atresia and further the development of clinical treatments.