Women’s fertility may decline with age due to altered RNA levels – sciencedaily

Age can adversely affect women’s fertility by altering the levels of RNA molecules which in turn alter the function of genes involved in key biological pathways during the final stage of maturation of a human egg, according to the researchers. results of a new study published today in the journal Aging cell.

Researchers from the Center for Genomic Regulation (CRG), Centro Nacional de Análisis Genómico (CNAG-CRG) and Clínica Eugin sequenced RNA molecules, also called transcriptome, in oocytes to understand which genes are affected in their activity according to age. They used single-cell sequencing to analyze the transcriptome of 72 individual oocytes from 37 donors aged 18 to 43.

They found that the number of transcripts for genes involved in chromosome segregation and RNA processing increased gradually with age, while the number of transcripts related to mitochondrial metabolism decreased.

However, these age-related transcriptome changes did not occur until the eggs reached their final stage of development during in vitro maturation. The transcriptome was less affected by age in immature eggs. According to the researchers, the results suggest that age may influence an oocyte’s ability to process essential gene products for the later stages of their development.

Further analysis revealed a number of potential master regulatory genes, which are genes at the top of a regulatory hierarchy, which are affected by age. Future work will verify whether these genes play a critical role in the aging of oocytes.

“Here we show that the final stage of oocyte maturation itself could be adversely affected by age, which is essential for reproduction because it provides the material that the first embryos need to develop normally and survive, ”says Bernhard Payer, AXA professor of age risk prediction. related diseases and group leader at the Center for Genomic Regulation (CRG) and co-author of the study. “What we don’t know yet is which of these changes are simply a consequence of the aging process and which may directly contribute to the decline in oocyte quality with age.”

The researchers also used height and weight information from donors to assess the impact of body mass index (BMI) on the transcriptome. Unlike age, abnormal BMI mainly affected the transcriptome of immature oocytes. According to the authors, the results suggest that the decline in fertility caused by age may have different root mechanisms than that caused by an abnormal BMI.

Women’s fertility generally declines with age. One of the main reasons for this is due to the depletion of ovarian reserves, as baby girls are born with all the eggs, from which mature eggs will develop, during their lifetime. Another reason is that the quality of eggs decreases with age, which is considered to be one of the main reasons for higher infertility rates after the age of 35. Being overweight or underweight has also been associated with poor oocyte quality and reproductive outcomes.

The authors conclude that while more studies are needed, their findings could lead to the future development of new diagnostic tools to better assess oocyte quality in reproductive medicine, as well as potential drug treatments that modulate affected pathways for rejuvenate aged oocytes.

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