Intact follicle culture: what it can tell us aabout the roles of FSH glycoforms during follicle development

Abstract

An important limiting factor in assisted reproduction treatment success rates is oocyte quality. In spite of improved results through several important innovations, the pregnancy rate per collected oocyte remains far too low. In order to improve this situation, it is necessary to learn more about fundamental factors modulating follicular development patterns. FSH is known to be the driving force for follicle development, but it is not yet understood how its multifarious functions are controlled and modulated. Evidence is accumulating that FSH glycoforms may be the key to this mystery. Intact follicle culture is a useful tool for the clarification of the actions of the different isoforms because the follicle unit is maintained and allowed to develop through several critical stages. Additionally important is the availability of the oocyte for functional evaluation. Because of these features, relationships can be uncovered that are not revealed with single cell test systems. The results so far obtained with this system suggest that follicle development pattern and oocyte quality is strongly influenced by FSH glycoform range, and that the requirements of the follicle may shift during progress through different stages of development. More studies are required, but these findings already suggest that the physiological shifts of circulating FSH glycoforms may indeed be important, and that attention should be paid to the glycoform distribution of exogenously applied FSH.

In vitro culture of sheep lamb ovarian cortical tissue in a sequential culture medium

“…That is to say, high concentrations of FSH and EGF and lower concentrations of GDF-9 and bFGF may be beneficial for the development of primary follicles. Studies on growth factors have demonstrated that FSH and EGF are not essential for primordial follicle activation [24][25][26] but are important for latter follicle development [1,14]. On the other hand, GDF-9 and bFGF can promote the initiation of primordial follicle development and stimulate early preantral follicle growth [5,6,8,[27][28][29].…”

“…Similarly, the various influences on the growth factors in ovarian follicle development have not been very uniform among different species. Studies have demonstrated the involvement of follicle-stimulating hormone (FSH) [1][2][3], growth and differentiation factor 9 (GDF-9) [4][5][6][7], basic fibroblast growth factor (bFGF) [8][9][10], insulin [11], and epidermal growth factor (EGF) [12][13][14] in early follicular development. Other factors that were incorporated in the present study are based on these references.…”

Effect of sialylation and complexity of FSH oligosaccharides on inhibin production by granulosa cells

“…Furthermore, it has been shown that the structure of oligosaccharides present in the FSH molecule induces a differential response in rat GCs in terms of oestradiol production . The pattern of follicular development and oocyte quality in mice are also strongly influenced by rhFSH sialylation (Nayudu et al 2002).…”

Sequential (hFSH + recFSH) vs homogenous (hFSH or recFSH alone) stimulation: clinical and biochemical (cumulus cell gene expression) aspects

“…FSH isoforms, i.e. protein variants with a different glycosylation profile [3][4][5], regulate distinct biological pathways and have specific effects on granulosa cell function and ovarian follicular maturation [6][7][8][9]. Dynamic changes in FSH isoforms occur during the follicular cycle with short-living forms predominating in the pre-ovulatory phase, whereas long-acting molecules characterize the luteal-follicular transition [10,11].…”