Ovarian Function/Dysfunction
Session: Poster Session C
Lauren N. DeCastro, n/a
Graduate assistant
Penn State Department of Animal Science
State College, Pennsylvania, United States
The ovarian reserve of follicles, which plays a critical role in determining lifelong fertility, is established during fetal development. Following the assembly of primordial follicles, they are activated to join the growing pool. This process occurs progressively throughout life but begins prior to or around the time of birth. Although the processes of primordial follicle assembly and activation are essential for fertility, their regulation is poorly understood, particularly in livestock species. This study was conducted to determine which metabolic pathways are active during earlier and later stages of ovarian development in cattle, to provide information on the regulation of ovarian reserve establishment and early follicular activation. Fetal ovaries were collected and snap frozen at a local slaughterhouse. Fetal age was determined based on crown-rump length of the fetus. The samples were grouped by age into two groups. The early group was aged 107-119 days gestation (n=5), during primordial follicle assembly. The late group was aged 161-169 days gestation (n=5), during early follicle activation. Based on this information we expect that the metabolites abundant in the early group would be associated with follicular assembly and early ovarian development while the metabolites abundant in the late group would be associated with follicular activation and tissue growth in the ovary. Untargeted liquid-chromatography mass- spectrometry metabolomics was run to evaluate the ovarian metabolome. Statistical analysis was performed using MetaboAnalyst 6.0 to determine which metabolites were differentially abundant between early and late ovaries. Of the 231 metabolites that were identified in the ovary, eleven of them were significantly different between the two groups (p< 0.05), among which six were greater in the early samples and five were greater in the late samples. Another nine metabolites tended to be different (p< 0.10), among which four were greater in the early samples and five were greater in the late samples. The three most significantly different metabolites were N-acetylhistidine (p=0.01; 8.8 fold greater in late ovaries), carnosine (p=0.01; 4.1 fold greater in late ovaries), and N-acetylaspartic acid (p=0.02; 4.1-fold greater in early ovaries). N-acetylhistidine and carnosine are both metabolites involved in histidine metabolism. N-acetylhistidine is synthesized from L-histidine by histidine N-acetyltransferase, with acetate generated from glucose metabolism. L-histidine is a precursor of carnosine, which can be converted back to L-histidine by carnosinase. Histidine is an essential amino acid, meaning it must be provided through diet. Although the role of histidine metabolism in the ovary is not clear, we hypothesize that changes in this metabolic pathway may help facilitate growth and tissue remodeling during follicular assembly, activation, and growth. Histidine is also a precursor for histamine and changes in histidine metabolism could mediate inflammation in the developing ovary. N-acetylaspartic acid, which was more abundant during follicular assembly, is a metabolite of alanine, aspartate, and glutamate metabolism and can provide acetyl groups for lipid biosynthesis. In summary, there is substantial modulation of the ovarian metabolome during development. Future studies will determine functional roles of these metabolites in primordial follicle formation and activation, providing potential targets for technology development to support fertility during ovarian aging. We are grateful to the Penn State Metabolomics core for performing the LC-MS. This study was supported by Penn State start-up funds to CHKH.