Declining ovarian reserve adversely influences granulosa cell viability

Characterizing the reproductive hormone milieu in infertile women with diminished ovarian reserve

“…Our findings of significantly lower urinary levels of estrogen (E) and P metabolites in a natural menstrual cycle in young infertile women with DOR are suggestive of ovarian GC dysfunction in these otherwise healthy and regularly cycling women. Although impairments in GC viability and proliferative indices are described in association with DOR (11)(12)(13)22), in the present study we provide evidence suggestive of altered reproductive hormone profile in women with DOR. Of interest are findings reported by Leach et al (23) using a similar paradigm of daily urinary hormone assessment, albeit in a different population of infertile women.…”

“…Quantitative and qualitative decline in the oocyte repertoire and a concomitant impaired granulosa cell (GC) efficiency are described in the context of DOR (11)(12)(13) and are suggested as contributors to the magnitude of subfertility in these women. Lower E 2 levels during attempts at ovarian hyperstimulation are well described, as is evidence of luteal dysfunction in association with DOR (3).…”

Women with reduced ovarian reserve or advanced maternal age have an altered follicular environment

“…In animal models, reduced levels of oocytesecreted factors, such as growth differentiation factor-9 and bone morphogenetic protein-15, result in decreased oocyte competence and changes in CC function, such as increased apoptotic markers (30). It has previously been demonstrated that GC viability is reduced with declining ovarian reserve and in our study CCs have increased gene expression of the apoptotic marker tumor protein 53 (31). Therefore, the levels of oocyte-secreted factors in women with reduced ovarian reserve or advanced maternal age warrant further investigation.…”

Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age

“…Recently, we have established that the follicular environment is altered in women with reduced ovarian reserve or advanced maternal age, suggestive of an environmental mechanism responsible for the reduced oocyte quality seen in these women (Pacella et al 2012). Furthermore, gene expression is altered in granulosa and cumulus cells collected from antral follicles of women with reduced ovarian reserve, indicating that an altered transcriptome may be a contributing factor in the reduction of fertility in these women (Greenseid et al 2009;May-Panloup et al 2012;Skiadas et al 2012). In support of this a recent study has demonstrated that granulosa cells from women with reduced ovarian reserve have altered mRNA expression of genes associated with metabolic pathways (Skiadas et al 2012).…”