Maternal metabolic health and female fertility: upregulated lipolysis and the consequences for in vitro bovine oviduct physiology and function
Lies Jordaens, DVM, PhD
Date: 18th of May, at 16h30
Location: ‘Promotiezaal’ (Building Q, Campus Drie Eiken)
Maternal metabolic health is a growing concern considering the rising incidences of obesity and associated metabolic disorders such as type II diabetes. In veterinary medicine, dairy cattle show similar trends for metabolic stress related disorders due to the advanced genetic selection for high milk producing cows which resulted in animals that are more prone to develop negative energy balance conditions. Earlier research indicated that maternal metabolic health and female fertility are closely linked. As such, metabolic stress is known to trigger hormonal imbalance, abnormal follicular development, and ovulatory dysfunction. Increased lipolysis and systemic elevations of non-esterified fatty acids are specific, though common traits during metabolic disorders. When expressed during the critical early embryo developmental stage, high levels of non-esterified fatty acids (NEFAs) can negatively affect embryo quality as well as resulting pregnancy, potentially even with a transgenerational outcome. As early embryo development takes place in the oviduct, the focus in this dissertation documents the impact of non-esterified fatty acids on the in vitro oviduct and its consequences for early embryo development.
We found that:
- Ex vivo oviductal NEFAs mirror plasma concentrations in healthy cattle.
- Pathological NEFA concentrations hamper in vitro BOEC functionality, but not morphology, in a polarity dependent manner.
- NEFAs can be either selectively transferred across the in vitro oviduct epithelium or intracellularly metabolized, impairing BOEC barrier function, transcriptome and fatty acid transporter expression differently depending on the NEFA exposure side.
- NEFAs reduce BOEC embryo-supportive and –protective features both directly and indirectly, therefore under lipotoxic conditions the embryotrophic capacity of the in vitro oviduct may be hampered though persists and can partially compensate direct lipotoxic effects of NEFAs exerted at the level of the embryo.
These findings may partially elucidate the reduced embryo supportive capacity in metabolically compromised individuals and suggest a crucial position for the oviduct in the pathogenesis of lipolysis induced female subfertility. However, to fully understand the loss in fertility during maternal lipolytic disorders, many more oviductal factors in addition to NEFAs need to be taken into consideration.