Identification of Lipids and Cytokines in Plasma and Follicular Fluid before and after Follicle-Stimulating Hormone Stimulation as Potential Markers for Follicular Maturation in Cattle

SIMPLE SUMMARY: The ovarian follicle contains an egg that must be matured appropriately to maintain regular reproductive cycles in cows and result in the ovulation of an egg capable of fertilization. Anovulation often occurs when there is poor follicle maturation. Lipids and cytokines in circulation and follicular fluid have been known to have an important role in follicular maturation. However, specific cytokine or lipid markers, or their role during stages of the cycle and when they are needed to provide optimal follicular maturation, have not been elucidated. The current study investigated the relationship between circulating and follicular fluid lipids and cytokines during an estrous cycle and after follicular stimulation with follicle-stimulating hormone. The identification of specific cytokines and lipids present at different stages of the reproductive cycle in circulation and the follicular fluid of the dominant follicle provides a springboard to study the mitigation of poor follicle maturation or anovulation. Future studies can also utilize the markers developed within this study to determine their role during follicular maturation. ABSTRACT: The process of follicle maturation leading to ovulation is a key milestone in female fertility. It is known that circulating lipids and cytokines play a role in the follicle’s ability to go through follicular maturation and the ovulatory processes. However, the specific mechanisms are not well understood. We posit that dysregulation of granulosa cells influences the ovarian environment, which tries to adapt by changing released lipids and cytokines to achieve follicular maturation. Eleven non-lactating adult females underwent estrus synchronization with two injections of PGF2α 14 days apart. Daily blood samples were collected for 28 days to monitor steroid hormone production after the second injection. To understand the potential impacts of lipids and cytokines during ovulation, a low-dose FSH stimulation (FSHLow) was performed after resynchronization of cows, and daily blood samples were collected for 14 days to monitor steroid hormone production until ovariectomies. The lipidomic analysis demonstrated increased circulating diacylglycerides and triacylglycerides during the mid-luteal phase and after FSHLow treatment. Cholesteryl esters decreased in circulation but increased in follicular fluid (FF) after FSHLow. Increased circulating concentrations of TNFα and reduced CXCL9 were observed in response to FSHLow. Therefore, specific circulating lipids and cytokines may serve as markers of normal follicle maturation.