COD is one of the most common and costly reproductive diseases affecting dairy cows in their reproductive journals. Although many publications exist on COD, the causes of the disease remain unclear. The condition is characterized by failure of the large permanent ovarian follicles to ripen and release eggs that would be fertile to cause conception in the cows, hence leading to infertility or subfertility in the cows. Although, the specific cause of COD is still under investigation, current studies have put emphasis or regards the part that cytokines have to play in the development of this disease. Recognition of the roles of cytokines in COD, not only offers a deeper knowledge of the molecular pathology of the disease but also marks out directions for the development of new therapeutic approaches to enhance the reproductive efficiency in dairy farms.
The Pivotal Role of Cytokines in Bovine Cystic Ovarian Disease: Pathogenesis, Implications, and Therapeutic Potential
Yearwise Publication Trend on “cystic ovarian disease”
Understanding Bovine Cystic Ovarian Disease (COD)
COD is a multifactorial disease in cows that involves the reproductive system particularly leading to cyst formation in the ovaries. These are fluid-filled structures that occur on the ovaries and can stay on for some time thus causing a disturbance of the normal estrous cycle. Cows with COD show abnormal oestrous cycle, prolonged anoestrus and low fertility rates; this makes COD a great threat to dairy producers.
The exact cause or causes of COD are still not known but it is hypothesized that hormonal, metabolic and environmental factors may play a role. From among these, the cytokines have been considered to play a significant part in the manifestation and progression of COD. Interleukins are also involved in various functions of immunity which also involve inflammation and tissue remodeling which are also factors affecting the function of ovaries.
The Role of Cytokines in Ovarian Physiology
I think cytokines are a vast class of peptides that have been defined with reference to the actual process of cell signaling especially in an immune system. In the ovary cytokines play numerous physiological roles among which are folliculogenesis, ovulatory process, and luteal phase. These molecules are secreted by a number of cell types within the ovary such as the granulosa cells, theca cells and immune cells and act in a paracrine/autocrine manner by binding to receptors on target cells.
Cytokines including TNF-α, ILs, and TGF-β also play a role in the follicular growth and development as well as follicular atresia. The elaboration of these cytokines assists in organizing relations between endocrine stimuli, inclining to gonadotropins (LH and FSH), and local factors of the ovary to select and to form the dominant follicles capable of ovulation.
Whereas, in the case of COD, it is likely that the homeostasis of cytokine may go out of whack within the ovary and could consequently manage to negatively regulate the healthy development of follicles and subsequently form persistent cysts.
Cytokine Dysregulation in COD
The studies have proven that cows with COD develop a change in the cytokine profile in their ovarian follicle. For instance, some investigations have found sooner pro-inflammatory cytokines than anti-inflammatory cytokines with regards to IL-1β and TNF- α in the follicular fluid of cystic ovary than in normal healthy follicle. These cytokines are involved in inflammation and can be hypothesized to be involved in the pathological changes seen in COD. Their effects may include a failure in follicle maturation and ovulation.
TNF-α has been particularly highlighted as having definite influence on the COD due to its effects in manipulating the functionality of the granulosa as well as the theca cells which play a very significant role in the development of follicles. TNF-α has been reported to cause apoptosis of granulosa cells resulting to detachment of the cells from the basal membrane and thus causing disruption of the structural … normal ovulation cannot also take place since the structural integrity of the follicle has been interfered with. Also, TNF-α can block the effect of gonadotropins, which in turn slows down the process of ovulation.
Another cytokine central to stroke and COD is IL-6, which is both pro- and anti-inflammatory. Utruration of IL-6 in cows with COD has been established where the cytokine is virtually present in the follicular in the fluids of the affected cows which makes it to be a potential Micheler of the chronic inflammation characteristic of the disease. IL-6 can also affect other cytokines and growth factors making a feedback that may contribute to the continuous development of the cystic condition.
Recent Publications on “cystic ovarian disease”
The Impact of Cytokines on Ovarian Follicular Dynamics
The results of cytokines’ dysregulation in COD are both negative effects on the structure of the ovarian follicles and changes in hormonal regulation within the ovary. Some cytokines like IL-1β and TNF- α can affect the steroidogenic enzymes and subsequently affect the ratio of sexy hormones like estrogen and progesterone. Thus, hormonal disturbances are characteristic of COD and can lead to the chronicity of ovarian cysts.
Specifically, IL-1β has been demonstrated to suppress the function of aromatase; this enzyme catalyze the convection of androgens to estrogens in granulosa cells. This means that with low aromatase activity, there will be low estrogen levels within the follicles which in turn interrupts the normal feedback loop that is responsible for follicular development and ovulation. Likewise, TNF-α also exerts an inhibitory effect on the secretion of progesterone from luteal cells thus causing luteal failure and tendency towards the formation of cysts.
Cytokines may also act to modulate the response of ovarian cells to gonadotropins during the process of cytokine-stimulatory or -inhibitory regulation. Some researchers have shown that pro-inflammatory cytokines can decrease the number of gonadotropin receptors in granulosa as well as theca cells and therefore, dull the sensitivity of these cells to LH and FSH. This low sensitivity to gonadotropins might compound the hormonal disturbances characteristic of COD and hamper the dissipation of ovarian cysts as well.
Therapeutic Implications: Targeting Cytokines in COD Management
Since cytokines are involved in the development of COD, it is possible to state that the management of the diseases may be developed by targeting these molecules. on approach could be the administration of anti-inflammatory agents or cytokine inhibitor to normalise the cytokine environment in the ovary and bring back normalism in the follicular wave.
For instance NSAIDs have been believed to have efficacy in the inhibition of cytokine synthesis and the amelioration of inflammation in the ovary. Thus, by reducing of the concentration of inflammatory factors, including TNF-α and IL-1β, NSAIDs may contribute to the normalization of follicular dynamics and resolution of ovarian cysts. However, the effectiveness of such treatments in the context of COD is still an open question and provokes more investigations to find the best approach to the therapy.
Another possible method of treatment is the administration of cytokine receptor antagonists or neutralizing antibodies against certain cytokines that are thought to play a part in COD. For instance, agents like TNF- α inhibitors which are used in treatment of inflammation related diseases in humans could be further used in treatment of cows with COD by promoting anti-apoptotic effects on the follicle in an attempt to enhance ovulatory functionality. Likewise, by utilizing IL-6 receptor antagonists, one may be able to influence inflammation within the ovaries and assist in clearance of cystic follicles.
However, in an effort to prevent cytokine dysregulation with its awful consequences, it may be an added advantage to look at other management strategies of dairy cows that can reduce the overall risk factors. This may involve enhancing diet, reducing stress, and proper reproductory related practices to maintain physiology and avoid development of COD.
Conclusion
Cytokines are involved in the process of ovarian cycle, and any disturbance of cytokine balance is one of the main causes of Cystic Ovarian Disease in dairy cows. Appreciation of cytokines, immune responses, and hormonal signaling that occur within the ovary during COD are crucial for the deployment of proactive approaches toward the condition’s prevention and management. If the cytokine pathways implicated in the COD pathophysiology were addressed, there may be an improved reproductive performance and therefore less burden on the dairy’s economy. Further study in this field will be vital to identify other treatments and proves useful in effective management of affected cows.
References
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- Shaham Y, Roth Z. Determination of Ovarian Cysts in Cattle with Poor Reproductive Performance Using Ultrasound and Plasma Progesterone Profile.
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- Gundling N, Drews S, Hoedemaker M. Comparison of Two Different Programmes of Ovulation Synchronization in the Treatment of Ovarian Cysts in Dairy Cows. Reprod Domest Anim. 2015 Dec; 50(6): 893-900. doi: 10.1111/j.1439-0531.2009.01342.x. Epub 2009 Mar 11. PMID: 19416488.
- Gaebler E, Eigenmann U, Bruckmaier R, Bleul U. Fate of follicular ovarian cysts in early postpartum dairy cows treated with PRID/PGF or PRID/PGF plus eCG. Tierarztl Prax Ausg G Grosstiere Nutztiere. 2015; 43(6): 331-9. English, German. doi: 10.15653/TPG-150249. Epub 2015 Nov 23. PMID: 26593336.