Reproductive Technology

Neutral Mitochondrial Heteroplasmy Alters Physiological Function in Mice

Abstract
Cytoplasmic transfer is an assisted reproductive technique that involves the infusion of ooplasm from a donor oocyte into a recipient oocyte of inferior developmental Competence. While this technique has shown some success for couples with recurrent IVF failure, it results in mitochondrial heteroplasmy in the offspring, defined as the presence of two different mitochondrial genomes in the same individual. Since the long-term health consequences of mitochondrial heteroplasmy are unknown, there is a need for appropriate animal models to evaluate any physiological changes of dual mitochondrial DNA genotypes. This longitudinal study was designed as a preliminary screen of basic physiological functions for heteroplasmic mice (NZB mitochondrial DNA on a Balb/cByJ background). The mice were tested for cardiovascular and metabolic function, hematological parameters, body mass analysis, ovarian reserve and tissue histologic abnormalities over a period of fifteen months. Heteroplasmic mice developed systemic hypertension that corrected over time and was accompanied by cardiac changes consistent with pulmonary hypertension. In addition, heteroplasmic animals also had increased body mass and fat mass compared to controls at all ages. Finally these animals had abnormalities in electrolytes and hematological parameters. Our findings suggest that there are significant physiological differences between heteroplasmic and control mice. Since ooplasm transfer appears to be consistently associated with mitochondrial heteroplasmy, children conceived through ooplasm transfer should be closely followed to determine if they are at risk for any health problems.

Key words: Ovary • Assisted Reproductive Technology • heteroplasmy • mitochondria • ooplasm transfer