Inter-follicular communication and the regulation of follicle dominance

• Main Author: Baker, Stuart James
• Published: University of Edinburgh 1999
• Subjects: 612.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641232

Further understanding of intra-ovarian interactions will help to determine how each species selects the correct number of follicles for continued development during ovulatory cycle. In an attempt to begin to extend our knowledge in this area, this thesis had two principle goals: I. establish if direct contact between follicles may play a part in the selection of the ovulatory follicles(s) <I>vivo,</I> and if this appeared to be the case, II. To investigate the precise nature of direct follicle-follicle communication in <I>vivo </I>and <I>in vitro.</I> I. To investigate how follicles are positioned in respect to one another in <I>vivo</I>, histological sections from a diverse range of mammalian species were examined, which clearly demonstrated that follicles are closely positioned in the ovary. Furthermore, a numerical analysis of mouse ovaries was undertaken and revealed that follicle 'clusters' are the norm in young mice. II. Investigations branched at this point. a) Culture experiments that regulated follicle-follicle contact determined that there was not an absolute requirement for contact to establish dominance, providing evidence for a very locally acting diffusible factor. b) A molecular approach was taken in an attempt to identify possible genes involved in juxtacrine communication between follicles. c) Other experiments examined the role of FSH and LH as survival factors for follicles at different stages of development, using apoptotic laddering of genomic DNA as a sensitive assay for atresia. Early follicles were unable to utilise LH and became apoptotic in low levels of FSH, in contrast with the more mature antral follicles that remained healthy when provided with LH in these low FSH concentrations. These observations have implications for follicle selection, with the possibility that inter-follicular communication could result in a subordinate follicle being held in a retarded stage of development rendering it vulnerable to decreased systemic FSH. In conclusion this thesis has demonstrated that geography-dependent follicle-follicle communication is feasible <I>in vivo</I>. Culture experiments demonstrated that it has a diffusible component and can be effected by the gonadotrophin environment of the follicle. Additionally the <I>Notch</I> family of neuro-genes were shown to be present in the ovary, although their expression and function remains to be clarified.