The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation

Abstract

Objective: To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity.

Design: Prospective observational study.

Setting: IVF clinic in a tertiary academic care center.

Patient(s): One hundred two oocytes from 32 women undergoing IVF.

Intervention(s): None.

Main outcome measure(s): Adenosine triphosphate (ATP) levels, mtDNA number, and mtDNA deletion occurrence in individual oocytes.

Result(s): Oocyte ATP content increases with maturation (786 ± 87 fmol, 1,037 ± 57 fmol, and 1,201 ± 59 fmol for prophase 1 [P1], metaphase 1 [M1], and metaphase 2 [M2] oocytes, respectively), whereas mtDNA copy numbers do not change (64,500 ± 20,440, 180,000 ± 44,040, and 143,000 ± 31,210 for P1, M1, and M2 oocytes, respectively). Stepwise multiple regression analysis identified developmental stage as a determinant of oocyte ATP, whereas number of oocytes retrieved and cycle day 3 FSH level were determinants of mtDNA copy number. Of the 15 oocytes found to possess the 5-kb mtDNA deletion, 10 were arrested or degenerated oocytes.

Conclusion(s): Although no direct association was found between female age and oocyte mitochondrial quantity and function, the number of mitochondria was predicted by ovarian reserve indicators. As the oocyte matures, ATP content increases.