Free fatty acid levels in fluid of dominant follicles at the preferred insemination time in dairy cows are not affected by early postpartum fatty acid stress

Aardema, Hilde; Gadella, Bart M.; Lest, Chris H.A. van de; Brouwers, Jos F.; Stout, T.A.E.; Vos, P.L.A.M.

doi:10.3168/jds.2014-7970

Cited by 19 publications

(21 citation statements)

References 44 publications

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“…Thus, to determine if elevated intrafollicular concentrations of free fatty acids affect GC functionality and thus may contribute to declined fertility rates as experienced by cows during NEB, in the present study, we analyzed the in vitro effects of major free fatty acids both separately and in combination on GC functionality. The tested concentrations of PA, SA and OA were based on earlier in vivo experiments which provided estimated physiological concentrations of free fatty acids in the follicular fluid of short-term fasted cows (22). Additionally, we knew from earlier reports that concentrations of OA is highest in the follicular fluid of cows and the present data showed that GC functionality is adversely modulated in vitro ; thus, we specifically selected OA for intrafollicular injection to validate whether the effects of OA observed in our GC culture model can be transferred to the in vivo situation.…”

Section: Discussionmentioning

confidence: 99%

Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

Sharma

Baddela

Becker

et al. 2019

Endocrine Connections

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High-yielding dairy cows postpartum face the challenge of negative energy balance leading to elevated free fatty acids levels in the serum and follicular fluid thus affecting the ovarian function. Here, we investigated effects of physiological concentrations of palmitic acid (PA), stearic acid (SA) and oleic acid (OA) on the viability, steroid production and gene expression in a bovine granulosa cell (GC) culture model. Treatment with individual and combined fatty acids increased the CD36 gene expression, while no significant apoptotic effects were observed. Both PA and SA significantly upregulated the expression of FSHR, LHCGR, CYP19A1, HSD3B1, CCND2 and increased 17β-estradiol (E2) production, while OA downregulated the expression of these genes and reduced E2. Interestingly, STAR was equally downregulated by all fatty acids and combination treatment. E2 was significantly reduced after combination treatment. To validate the effects of OA, in vivo growing dominant follicles (10–19 mm) were injected with bovine serum albumin (BSA) with/without conjugated OA. The follicular fluid was recovered 48 h post injection. As in our in vitro model, OA significantly reduced intrafollicular E2 concentrations. In addition, expression of CD36 was significantly up- and that of CYP19A1 and STAR significantly downregulated in antral GC recovered from aspirated follicles. The ovulation rates of OA-injected follicles tended to be reduced. Our results indicate that elevated free fatty acid concentrations specifically target functional key genes in GC both in vitro and in vivo. Suggestively, this could be a possible mechanism through which elevated free fatty acids affect folliculogenesis in dairy cows postpartum.

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Section: Discussionmentioning

confidence: 99%

Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

Sharma

Baddela

Becker

et al. 2019

Endocrine Connections

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“…This result has also been found in other cell types in which SCD expression could be stimulated by several metabolites, including saturated and monounsaturated free fatty acids [ 24 , 36 ]. Interestingly, the observed higher oleic acid to stearic acid ratio in follicular fluid when compared to the levels in blood [ 1 , 3 , 37 ] may be explained by follicular SCD activity in granulosa and cumulus cells.…”

Section: Discussionmentioning

confidence: 99%

Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress

Aardema

Tol

Wubbolts

et al. 2017

Biology of Reproduction

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Metabolic rich and poor conditions are both characterized by elevated free fatty acid levels and have been associated with impaired female fertility. In particular, saturated free fatty acids have a dose-dependent negative impact on oocyte developmental competence, while monounsaturated free fatty acids appear less harmful. Cumulus cells seem to protect the oocyte against free fatty acids, and the aim of this study was to determine the mechanism behind this protection In particular, the role of the enzyme stearoyl-CoA desaturase (SCD) that converts saturated into monounsaturated fatty acids was investigated. SCD gene and protein were abundantly expressed in cumulus cells, but expression was low in oocytes. The level of SCD protein expression in cumulus cells did not change when COCs were exposed to saturated stearic acid during maturation. SCD inhibition in the presence of stearic acid significantly reduced the developmental competence of oocytes and increased the incidence of apoptosis in cumulus cells. The esterified oleic/stearic acid ratio of the neutral lipid fraction in cumulus cells decreased in the presence of SCD inhibitors when COCs were exposed to saturated free fatty acids during maturation, indicating the SCD-specific conversion of saturated fatty acids under noninhibiting conditions. The observation that cumulus cells can desaturate the potentially toxic stearic acid into oleic acid via SCD activity provides a mechanistic insight into how the cumulus cells protect the oocyte against toxicity by saturated fatty acid.

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“…Palmitic acid (PA) is one of the most common fatty acids in animal and human follicular fluid (FF) and blood serum [1–3]. The PA level in mammalian FF is reported to be approximately 10 − 4 M [3–5]. Recently, increasing evidence has shown that elevated PA levels may be associated with infertility in humans [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

et al. 2019

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Background Palmitic acid (PA), the main component of dietary saturated fat, causes apoptosis in many cell types, including mouse granulosa cell. Melatonin, an important endogenous hormone, has beneficial effects on female reproductive processes. Since elevated PA levels are present in follicular fluid (FF) of patients with infertility and are shown to be toxic for granulosa cells, we investigated the molecular mechanisms of PA toxicity in mouse granulosa cells and explored the effects of melatonin on PA-induced apoptosis. Methods Granulosa cells from immature female mice were cultured for 24 h in medium containing PA and/or melatonin. Then, the effects of PA alone or combined with melatonin on viability, apoptosis and endoplasmic reticulum (ER) stress in granulosa cells were detected by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry assay and western blot. After 48 h of PA and/or melatonin treatment, the concentrations of estradiol (E2) and progesterone (P4) in the culture supernatants were measured with ELISA kits. Results In this study, we explored the effects of melatonin on cell viability and apoptosis in PA-treated mouse granulosa cells and uncovered the signaling pathways involved in these processes. Our results showed that 200-800 μM PA treatment reduces cell viability, induces cell apoptosis, enhances the expression of apoptosis-related genes (Caspase 3 and B-cell lymphoma-2 (BCL-2) associated X protein (BAX)), and activates the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Melatonin treatment (1-10 μM) suppresses 400 μM PA-induced cell viability decrease, cell apoptosis, Caspase 3 activation, and BAX, CHOP, and GRP78 expression. In addition, we found that 10 μM melatonin successfully attenuated the 400 μM PA-induced estrogen (E2) and progesterone (P4) decreases. Conclusions This study suggests that PA triggers cell apoptosis via ER stress and that melatonin protects cells against apoptosis by inhibiting ER stress in mouse granulosa cells. Electronic supplementary material The online version of this article (10.1186/s13048-019-0519-z) contains supplementary material, which is available to authorized users.

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Free fatty acid levels in fluid of dominant follicles at the preferred insemination time in dairy cows are not affected by early postpartum fatty acid stress

Cited by 19 publications

References 44 publications

Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress

Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

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