During stress, the hypothalamic-pituitary-adrenal (HPA) axis is activated. Hypothalamic neurons within the HPA axis secrete corticotropin-releasing hormone that causes the release of adrenocorticotrophic hormone (ACTH) from the pituitary. The ACTH causes the adrenal gland to secrete cortisol (a stress hormone). Cortisol will initially improve an animal's ability to cope with stress. Long-term increases in cortisol, however, are unhealthy. The hormone responsible for reproduction is gonadotropin-releasing hormone (GnRH). GnRH is released from the hypothalamus and causes the release of luteinizing hormone (LH) from the pituitary. The release of LH stimulates ovarian follicular growth and ovulation (essential processes for reproduction). Physiological and psychological stressors will typically inhibit GnRH and LH release. Some stressors activate the HPA axis (i.e., increase cortisol) and inhibit GnRH and LH through an HPA-dependent mechanism. Other stressors including postpartum negative energy balance have inhibitory effects on GnRH and LH but act through pathways that do not involve the HPA axis. A certain amount of management-induced stress is unavoidable. The best reproductive performance will be achieved when stress is minimized so that the endocrine components of the reproductive axis can function at their maximal level.

Transcription profiling of ovarian follicles. Understanding the mechanisms by which a single follicle is selected for further ovulation is important to control fertility in mammals. However, development of new treatments is limited by our poor understanding of molecular mechanisms regulating follicular selection. Our hypothesis is that genes involved in the control of cell proliferation and apoptosis are differentially regulated during follicular selection. Our objective was to identify these new genes. Bovine follicles were collected and gene expression levels were measured using microarrays. First, follicles were allocated to three groups, according to the time spent from the initiation of follicular wave to surgery (24 H, 36 H, and 48-60 H). Fifty-seven genes are differentially expressed at a false discovery rate of 5%. These genes are involved in the control of lipid metabolism (P-value = 0.0005), cell proliferation (0.007), cell death (0.003), cell morphology (0.003), and immune response (0.003). Follicles were also grouped into four categories, according to the expected time of deviation (early deviation; 8 mm, mid-deviation; 8.5 mm, late deviation; 9 mm, dominant follicles; 10 mm). One hundred and twenty eight genes are differentially expressed between these four groups, including genes involved in cell proliferation (0.00002), cell death (0.0006), cell-to-cell signaling (0.003) cell, morphology (0.003), lipid metabolism (0.0004), and immune response (0.00007). The expression levels of 10 genes were confirmed using quantitative real time PCR. As expected, we identified new differentially regulated genes involved in the control of cell growth and apoptosis. We also discovered a potential role for immune cells, and in particular macrophages, in follicular selection.

In mono-ovulatory species, one follicle is selected from a cohort of antral follicles to continue its growth and development. The other follicles from the cohort will ultimately undergo atresia. Understanding the mechanisms by which a single follicle is selected for further development and dominance in a hormonal milieu suppressive to the development of other large follicles is key to understanding preovulatory follicular development. Microarrays (17,692 cDNA probes) were used to identify genes differentially expressed among fourteen bovine follicles (8 to 11.5mm in diameter). First, follicles were organized in three groups according to the time from initiation of the wave (24H, 36H, 48–60H). Fifty nine genes (59) were identified as differentially expressed with a cut off false discovery rate (FDR) of 0.05 (adjusted for multiple testing) and a minimum of 40% up or down-regulation. Genes involved in immune related functions are up regulated in the 36 hour group. Genes regulating cell division/cell cycle and cell/extracellular matrix attachment were up or down regulated in the 36 and 48/60 hour groups. Follicles were also grouped according to the estimated time of deviation; early deviation (8 mm), middle deviation (8.5mm), late deviation (9mm) and dominant follicles (>9mm). One hundred and seventy six (176) differentially expressed genes were identified. Genes involved in immune-related functions and the mitotic cell cycle were up-regulated in the middle and late deviation groups. Annotation of the cellular location of the products identified non-membrane-bound organelle and the extracellular matrix as over-represented. Finally, fifty five genes have an expression pattern highly positively correlated with the expression of the LH receptor and ninety eight genes are negatively correlated. Expression profiles of seventeen genes were confirmed using quantitative RT-PCR. (poster)

Ovarian follicular cysts are anovulatory follicular structures that occur in 10 to 13% of dairy cows. This review focuses upon the dynamics of cyst growth, development, and persistence as well as on associated endocrine and cellular mechanisms. During the estrous cycle of cows, two to four waves of follicular growth occur. From a cohort of recruited follicles, one is selected for continued growth and dominance while the other undergo atresia and regress. In contrast, cysts have long been thought to be static structures that persist for extended periods. Although cysts can persist for extended periods, most regress over time and are replaced during subsequent follicular waves. The next dominant follicle either ovulates or develops into a new cyst. The recruitment of a cohort of follicles from which a cyst develops and the growth rate of cysts to ovulatory size are similar to ovulatory follicular waves, but the cyst continues to grow for a longer period. The interval between waves of follicular growth is longer for cows with cysts than for cows with normal estrous cycles. Each wave is preceded by a transient increase in circulating FSH. Near the time of cyst development and persistence, the concentration of FSH is not different from that during normal estrous cycles. Serum concentrations of LH and estradiol-17 beta are higher in cows that develop cysts than in cows that do not. Conversely, hypothalamic content of GnRH is lower in cows with cysts. Thus, cysts are dynamic structures, and their development and lifespan are likely associated with altered hypothalamic-hypophysial-ovarian function.