Altered expression of IL-1β, IL-1RI, IL-1RII, IL-1RA and IL-4 could contribute to anovulation and follicular persistence in cattle

Stassi, Antonela Florencia; Baravalle, María Eugenia; Belotti, Eduardo Matías; Amweg, Ayelén Noelia; Angeli, Emmanuel; Velázquez, Melisa María del Luján; Rey, Florencia; Salvetti, Natalia Raquel; Ortega, Hugo Héctor

doi:10.1016/j.theriogenology.2017.12.048

Cited by 18 publications

(15 citation statements)

References 97 publications

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“…Previous studies had shown that cytokines are master modulators of the follicle milieu and fate, controlling cell proliferation, follicular development, atresia, ovulation, steroidogenesis, and angiogenesis (13–15). Our findings are consistent with previous studies using persistent follicle models that reveal increased mRNA expression of IL-1RA, IL-1RII, IL-4, IL-6, IL-8, and TNF depending on the length of persistence (3, 17). A single study characterized pro-inflammatory cytokines in cows with spontaneous COF, revealing no differences in mRNA expression of IL-1β, IL-6, and TNF (16).…”

Section: Discussionsupporting

confidence: 93%

“…Another key dysregulation reported in cows with COF is the expression of immunological markers such as cytokines – key regulators of cell proliferation, follicular development, atresia, ovulation, steroidogenesis, and angiogenesis (13–15). Few investigations were performed with dairy cows, using either a model with induced follicle persistence or naturally occurring COF (3, 16, 17). The first study using a model of persistent follicles (5, 10 and 15 days of follicular persistence with day 0 as expected ovulation) revealed that interleukin 8 ( IL-8) and tumor necrosis factor-α ( TNF) was higher early (0 and/or 5 days of follicular persistence), and IL-6 was higher from 0 to 10 days of persistence, in relation to dominant follicles from the control group (3).…”

Section: Introductionmentioning

confidence: 99%

“…The first study using a model of persistent follicles (5, 10 and 15 days of follicular persistence with day 0 as expected ovulation) revealed that interleukin 8 ( IL-8) and tumor necrosis factor-α ( TNF) was higher early (0 and/or 5 days of follicular persistence), and IL-6 was higher from 0 to 10 days of persistence, in relation to dominant follicles from the control group (3). A second study of persistent follicles found that persistent follicles at different stages of persistence had a higher expression of IL-1 receptor antagonist ( IL-1RA ), IL-1 receptor II ( IL-1RII ), and IL-4 than the control group (17). The single study characterizing pro-inflammatory cytokines in cows with spontaneous COF, revealed that there was no differences in mRNA expression of IL-1 β , IL-6 , and TNF measured by real-time polymerase chain reaction between cystic follicles and dominant follicles, but the expression of these pro-inflammatory cytokines was higher in cystic follicles when measured by immunohistochemistry (16).…”

Section: Introductionmentioning

confidence: 99%

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Steroidogenic, Metabolic, and Immunological Markers in Dairy Cows Diagnosed With Cystic Ovarian Follicles at Early and Mid-Late Lactation

et al. 2019

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The etiology of cystic ovarian follicles (COF) remains a conundrum with steroidogenic, immunological, and metabolic dysfunctions linked to its development. Studies suggest that COF development may occur as a result of disruption of the insulin signaling pathway and the severity of a negative energy balance in dairy cows, but mid to late lactation cows diagnosed with COF are unlikely to have issues with energy metabolism. Herein, we characterized the mRNA expression of steroidogenic (LHCGR, StAR, CYP11A1, 3β-HSD, CYP19A), immunological (IL-1β, IL-6, IL-8, TLR-4, TNF), and metabolic markers (IGF-1, IRS1) in follicular fluid; and plasma and follicular fluid levels of E2, IL-1β, glucose, and NEFA in early and mid-late lactation COF cows. Lactating dairy cows were diagnosed as having COF (n = 11, follicle >20 mm persistent for 7 days, absence of corpus luteum, and flaccid uterus) while 11 herdmates cycling with a dominant follicle were classified as the control cows. Cows diagnosed with COF were classified as early lactation (COF-E, n = 5) cows, <35 days in milk (DIM); or mid-late lactation (COF-M/L, n = 6), ≥118 DIM cows. Results revealed that mRNA expression StAR was greater (P < 0.01) in COF-E cows than COF-M/L cows and the control cows. The mRNA expression CYP19A1 was lower (P < 0.01) in COF-E cows and COF-M/L cows than in the control cows. The mRNA expression IL-6 and IRS-1 tended to be greater and lower, respectively, in COF-M/L cows compared to the control cows. The mRNA expression IGF-1 was greater (P < 0.01) in COF-E and COF-M/L cows than in the control cows. The plasma and follicular fluid concentration of NEFA was greater (P < 0.05) in COF-E cows than in COF-M/L and the control cows. Cows with COF-E had disturbances in steroidogenic and metabolic markers, while cows with COF-M/L had steroidogenic, immunological, and metabolic dysregulations, suggesting that COF pathogenesis may vary between early and mid-late lactation dairy cows.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Steroidogenic, Metabolic, and Immunological Markers in Dairy Cows Diagnosed With Cystic Ovarian Follicles at Early and Mid-Late Lactation

et al. 2019

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“…Ovulation is similar to an inflammatory cytokine-mediated response (99, 100) and is associated with an increase in vasodilation, production of prostaglandin, cell proliferation, and secretion of tissue as well as local growth regulatory factors (101, 102). Some studies have suggested that the innate immune system is active in connection with ovulation (101–103). Cytokines are both key modulators of the immune system and contribute to regulation of the ovarian cycle.…”

Section: Inflammation Can Affect Granulosa and Theca Cells Which May mentioning

confidence: 99%

Perturbations in Lineage Specification of Granulosa and Theca Cells May Alter Corpus Luteum Formation and Function

et al. 2019

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Anovulation is a major cause of infertility, and it is the major leading reproductive disorder in mammalian females. Without ovulation, an oocyte is not released from the ovarian follicle to be fertilized and a corpus luteum is not formed. The corpus luteum formed from the luteinized somatic follicular cells following ovulation, vasculature cells, and immune cells is critical for progesterone production and maintenance of pregnancy. Follicular theca cells differentiate into small luteal cells (SLCs) that produce progesterone in response to luteinizing hormone (LH), and granulosa cells luteinize to become large luteal cells (LLCs) that have a high rate of basal production of progesterone. The formation and function of the corpus luteum rely on the appropriate proliferation and differentiation of both granulosa and theca cells. If any aspect of granulosa or theca cell luteinization is perturbed, then the resulting luteal cell populations (SLC, LLC, vascular, and immune cells) may be reduced and compromise progesterone production. Thus, many factors that affect the differentiation/lineage of the somatic cells and their gene expression profiles can alter the ability of a corpus luteum to produce the progesterone critical for pregnancy. Our laboratory has identified genes that are enriched in somatic follicular cells and luteal cells through gene expression microarray. This work was the first to compare the gene expression profiles of the four somatic cell types involved in the follicle-to-luteal transition and to support previous immunofluorescence data indicating theca cells differentiate into SLCs while granulosa cells become LLCs. Using these data and incorporating knowledge about the ways in which luteinization can go awry, we can extrapolate the impact that alterations in the theca and granulosa cell gene expression profiles and lineages could have on the formation and function of the corpus luteum. While interactions with other cell types such as vascular and immune cells are critical for appropriate corpus luteum function, we are restricting this review to focus on granulosa, theca, and luteal cells and how perturbations such as androgen excess and inflammation may affect their function and fertility.

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“…Follicular cysts disease is one of the most common causes of reproductive failure or infertility in females. Follicular cysts can induce reproductive endocrine dysfunction in animals (Ono et al, ; Stassi et al, ; Zannoni, Bernardini, Soflai, Sohee, & Forni, ). RBP‐4 acts as the mediator for the systemic and intercellular transport of vitamin A (retinol).…”

Section: Discussionmentioning

confidence: 99%

Association of RBP‐4 gene polymorphisms with follicular cysts in large white sows

Wang

Chen

et al. 2019

Reprod Domestic Animals

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Follicular cysts, which is a common infertility disease, can cause financial losses in pig breeding programmes. The pathogenesis and mechanisms of the formation of follicular cysts are not understood clearly. In our previous study, the concentration of retinol‐binding protein 4 (RBP‐4) in the follicular fluid (FF) of the ovary with follicular cysts was found to be significantly higher than that of normal ovary, thereby suggesting that RBP‐4 may be a candidate biomarker for porcine follicular cysts. To study the association of RBP‐4 and follicular cysts further, we detected the polymorphisms of the RBP‐4 gene and the presence of follicular cysts by PCR‐Restriction fragment length polymorphism (RFLP) assay. In this study, we screened the mutations of RBP‐4 gene in 79 sows with follicular cysts and 100 normal sows without cysts. Results showed that +249‐63G>C polymorphisms were significantly associated with follicular cysts, and sows with CC genotype in RBP‐4 gene had a high risk of developing follicular cysts. Hence, our findings further proved that RBP‐4 may be a novel biomarker for follicular cysts, which may be valuable for the diagnosis of follicular cysts and molecular breeding of pigs.

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Altered expression of IL-1β, IL-1RI, IL-1RII, IL-1RA and IL-4 could contribute to anovulation and follicular persistence in cattle

Cited by 18 publications

References 97 publications

Steroidogenic, Metabolic, and Immunological Markers in Dairy Cows Diagnosed With Cystic Ovarian Follicles at Early and Mid-Late Lactation

Steroidogenic, Metabolic, and Immunological Markers in Dairy Cows Diagnosed With Cystic Ovarian Follicles at Early and Mid-Late Lactation

Perturbations in Lineage Specification of Granulosa and Theca Cells May Alter Corpus Luteum Formation and Function

Association of RBP‐4 gene polymorphisms with follicular cysts in large white sows

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