Infertility Research Paper

INTRODUCTION
Infertility is one of the major economic issues challenging the dairy industry today [1]. Currently in the United States, expenses attributed to dairy cow infertility are estimated to exceed $350M per year [2]. Infertility is the absence of pregnancy after 12 months of breading attempt [3]. There are numerous causes of infertility in cattle, including infectious diseases, anatomical abnormalities, physical trauma, environmental toxins, and anovulation [4]. Among these, anovulation, or the failure to ovulate, is one of the most significant causes of infertility [5].
Ovulation is a complex biological process that is initiated by a surge of luteinizing hormone secreted from the anterior pituitary that ultimately triggers the rupture
Furthermore, in the primate ovary, VEGF mRNA and protein expression were observed in the theca cells of the pre-ovulatory follicles, exemplifying an integral role of VEGF in folliculogenesis [15]. Even though VEGF expression is largely associated with tumorigenic potential, VEGF confers physiological functions as well [16]. The process of angiogenesis is restricted to pathological conditions such as tumor growth and metastasis and physiological conditions such as wound healing, inflammation and female reproductive processes such as, placentation, follicular development and corpus luteum formation
One of the ways to downregulate VEGF secretion is by downregulating the cellular sources of VEGF. In other words, we can downregulate VEGF at its source by downregulating immune cells, such as macrophages via immunosuppressant such as dexamethasone (DEX), a glucocorticoid. Glucocorticoids, a group of corticosteroid exerts inhibitory effects on the various constituents of the immune system, ranging from B-cells and T-cells to macrophages and neutrophils [21]. Since its discovery, much has been learned about the mechanistic workings of DEX, but it is yet to be fully understood. The commonly accepted theory is that, glucocorticoids exert their effect at the molecular level by altering gene expression. Glucocorticoids such as DEX bind with its receptor (glucocorticoid receptor), which is a transcription factor that influences gene expression by either upregulating or downregulating certain genes [22]. DEX in particular suppresses the immune system by binding to its receptors, which in turn downregulates the expression of proinflammatory genes by blocking nuclear factor kappa B (NF-kB) and upregulates the expression of anti-inflammatory genes [23-24]. Furthermore, DEX can downregulate the extravasation of monocytes, macrophages and other innate immune cells to tissues