Impaired insulin signaling pathways affect ovarian steroidogenesis in cows with COD

Gareis, Natalia Carolina; Huber, Emilia; Hein, Gustavo Juan; Rodríguez, Fernanda Mariel; Salvetti, Natalia Raquel; Angeli, Emmanuel; Ortega, Hugo Héctor; Rey, Florencia

doi:10.1016/j.anireprosci.2018.03.031

Cited by 25 publications

(23 citation statements)

References 60 publications

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“…Compared with GCs of follicular cysts in cows, a recent study reported that INSR and PI3K were significantly higher expressed in GCs of control antral follicles. This indicated INSR and PI3K might involve in the regulation of steroidogenic enzymes expression [42].…”

Section: Discussionmentioning

confidence: 93%

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

Zhou

Jiang

et al. 2020

Asian-Australas J Anim Sci

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Objective: Numerous studies have indicated that the apoptosis and proliferation of granulosa cells (GCs) are closely related to the normal growth and development of follicles and ovaries. Previous evidence has suggested that miR-126-3p might get involved in the apoptosis and proliferation of GCs, and phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2) gene has been predicted as one target of miR-126-3p. However, the molecular regulation of miR-126-3p on PIK3R2 and the effects of PIK3R2 on porcine GCs apoptosis and proliferation remain virtually unexplored.Methods: In this study, using porcine GCs as a cellular model, luciferase report assay, mutation and deletion were applied to verify the targeting relationship between miR-126-3p and PIK3R2. Annexin-V/PI staining and 5-ethynyl-2’-deoxyuridine assay were applied to explore the effect of PIK3R2 on GCs apoptosis and proliferation, respectively. Real-time quantitative polymerase chain reaction and Western Blot were applied to explore the regulation of miR-126-3p on PIK3R2 expression.Results: We found that miR-126-3p targeted at PIK3R2 and inhibited its mRNA and protein expression. Knockdown of PIK3R2 significantly inhibited the apoptosis and promoted the proliferation of porcine GCs, and significantly down-regulated the mRNA expression of several key genes of PI3K pathway such as insulin-like growth factor 1 receptor (IGF1R), insulin receptor (INSR), pyruvate dehydrogenase kinase 1 (PDK1), and serine/threonine kinase 1 (AKT1).Conclusion: MiR-126-3p might target and inhibit the mRNA and protein expressions of PIK3R2, thereby inhibiting GC apoptosis and promoting GC proliferation by down-regulating several key genes of the PI3K pathway, IGF1R, INSR, PDK1, and AKT1. These findings would provide great insight into further exploring the molecular regulation of miR-126-3p and PIK3R2 on the functions of GCs during the folliculogenesis in female mammals.

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Section: Discussionmentioning

confidence: 93%

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

Zhou

Jiang

et al. 2020

Asian-Australas J Anim Sci

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“…For example, Red Angus cattle are known to be a highly fertile breed with exceptional maternal characteristics 65 . We identify the "ovarian steroidogenesis" pathway under selection, a potential driver of hormone balance and female fertility 66,67 . We also identify numerous other processes involved in the production and metabolism of hormones.…”

Section: Directional Selection For Production Traits Acts On Similar mentioning

confidence: 99%

Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattle

Rowan

Durbin

Seabury

et al. 2020

Preprint

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Selection is a basic principle of evolution. Many approaches and studies have identified DNA mutations rapidly selected to high frequencies, which leave pronounced signatures on the surrounding sequence (selective sweeps). However, for many important complex, quantitative traits, selection does not leave these intense signatures. Instead, hundreds or thousands of loci experience small changes in allele frequencies, a process called polygenic selection. We know that directional selection and local adaptation are actively changing genomes; however we have been unable to identify the genomic loci responding to this polygenic, complex selection. Here we show that the use of novel dependent variables in linear mixed models (which allow us to account for population structure, relatedness, inbreeding) identify complex, polygenic selection and local adaptation. Thousands of loci are responding to artificial directional selection and hundreds of loci have evidence of local adaptation. While advanced reproduction and genomic technologies are increasing the rate of directional selection, local adaptation is being lost. In a changing climate, the loss of local adaptation may be especially problematic. These selection mapping approaches can be used in evolutionary, model, and agriculture contexts.

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“…The etiology of cystic ovarian follicles (COF) remains a puzzle, but hormonal, immunological, and metabolic imbalances have been linked to its development (1–5). Cows diagnosed with COF have a dysfunctional hypothalamic-pituitary-ovarian axis signature that includes parabasal concentration of progesterone, increased peripheral estradiol levels, increased LH pulse frequency and amplitude, and reduced LH and FSH receptors that translate into a lack of LH surge and ovulation (6–10).…”

Section: Introductionmentioning

confidence: 99%

“…A more recent study found a higher or lower protein expression steroid acute regulatory protein ( StAR) , cytochrome P450 aromatase ( CYP19A1) , and 3β-hydroxysteroid dehydrogenase ( 3 β -HSD) in the theca and granulosa cells of COF depending on the follicular stage of development (5). For example, the protein expression of CYP19A1 was lower in the preantral follicles of COF cows than in control cows, but CYP19A1 was higher in the antral follicles of COF cows than in the control cows suggesting that the criteria used for comparisons can impact the results and its interpretation for the development of COF (5). The number of days postpartum when COF are diagnosed, cyst turnover, and response to the therapy are revised and vary considerably (12).…”

Section: Introductionmentioning

confidence: 99%

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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Impaired insulin signaling pathways affect ovarian steroidogenesis in cows with COD

Cited by 25 publications

References 60 publications

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattle

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

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