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Genetic variants are known to contribute to about 50% of the heritability of the age of menopause and recent studies suggest that genes associated with genome maintenance are involved. The idea that increased rates of follicular atresia could lead to depletion of the primoridial follicle reserve and early menopause has also been canvassed, but there is no direct evidence of this. In studies of the transcriptomics of follicular atresia, it was found that in the theca interna, the largest group of genes are in fact down-regulated and associated with ‘cell cycle and DNA replication’, in contrast with the up-regulation of apoptosis-associated genes which occurs in granulosa cells. Many of the genes down-regulated in the theca interna are the same as or related to the genes in loci associated with early menopause. From these findings, we suggest that early menopause could be due to increased rates of follicular atresia initiated from the theca interna.

Genetic relationships between early menopause and the behaviour of theca interna during follicular atresia