Lipopolysaccharide enhances apoptosis of corpus luteum in isolated perfused bovine ovaries in vitro

Lüttgenau, Johannes; Möller, Benjamin; Kradolfer, David; Wellnitz, Olga; Bruckmaier, Rupert M.; Miyamoto, Akio; Ulbrich, Susanne E.; Bollwein, Heinrich

doi:10.1530/rep-15-0281

Cited by 14 publications

(33 citation statements)

References 63 publications

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“…Binding and activation of TLR4 initiates the production of proinflammatory cytokines and leads to the recruitment of leukocytes . However, in the recent study (Lüttgenau et al 2016) that used isolated perfused ovaries, luteal mRNA expression of TLR4 did not differ between LPS-treated and control ovaries during the first 3 hours after treatment. Apart from the differences in the general approach of the recent and the present study (in vitro vs in vivo), the different outcome in luteal expression of several factors that were investigated in both studies might be due to the different sampling time.…”

Section: Discussionmentioning

confidence: 72%

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Lüttgenau¹,

Herzog²,

Strüve³

et al. 2016

Reproduction

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When given intravenously (iv), lipopolysaccharide (LPS) transiently suppresses the structure and function of the bovine corpus luteum (CL). This is associated with increased release of prostaglandin (PG) F 2a metabolite. The underlying regulatory mechanisms of this process remain, however, obscure. Therefore, the aims of this study were: i) to investigate the expression of the LPS receptor toll-like receptor 4 (TLR4) and 2 (TLR2) in the bovine CL during early, mid-and late luteal phases; and ii) to further dissect the mechanisms of LPS-mediated suppression of luteal function. As revealed by semi-quantitative qPCR and immunohistochemistry, both receptors were detectable throughout the luteal lifespan. Their mRNA levels increased from the early toward the mid-luteal phase; no further changes were observed thereafter. The TLR4 protein seemed more highly represented than TLR2. The cellular localization of TLRs was in blood vessels; weaker signals were observed in luteal cells. Additionally, cows were treated either with LPS (iv, 0.5 mg/kg BW) or with saline on Day 10 after ovulation. Samples were collected 1200 h after treatment and on Day 10 of the respective subsequent (untreated) cycle. The mRNA expression of several possible regulatory factors was investigated, revealing the suppression of PGF 2a receptor (PTGFR), STAR protein and 3b-hydroxysteroid dehydrogenase, compared with controls and subsequent cycles. The expression of TLR2 and TLR4, interleukin 1a (IL1A) and 1b (IL1B) and of PGF 2a and PGE 2 synthases (HSD20A and mPTGES respectively) was increased. The results demonstrate the presence of TLR2 and TLR4 in the bovine CL, and implicate their possible involvement in the deleterious effects of LPS on its function.

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Section: Discussionmentioning

confidence: 72%

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Lüttgenau¹,

Herzog²,

Strüve³

et al. 2016

Reproduction

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“…We therefore speculated that UPR may be involved in the process of goat luteal cells dividing from follicular granulosa cells and theca cells. The regression of the CL occurs in the late luteal phase of the goat CL and is accompanied with the apoptosis of the luteal cells stimulated by PGF2α ( Tanaka et al, 2000 ; Diaz et al, 2002 ; Luttgenau et al, 2016 ; Kim et al, 2019 ). A previous study revealed that the caspase-dependent apoptosis pathway was significantly activated in bovine CL after PGF2α-injection ( Kliem et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy

Wen

Liu

et al. 2020

Front. Physiol.

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Corpus luteum (CL) is a transient endocrine tissue that produces progesterone for maintaining pregnancy in mammals. In addition, the regression of CL is necessary for the initiation of the estrous cycle. Extensive research has shown that the prostaglandin F2α (PGF2α) induces the regression of CL in ruminants. However, the mechanisms of endoplasmic reticulum (ER) stress and autophagy in the regression of goat CL induced by PGF2α are still unclear. In this study, ovaries of dioestrus goats and goats that were 3 months pregnant were collected to detect the location of the ER stress-related protein GRP78. The relationship between the different stages of the luteal phase of goat CL during the estrous cycle and changes in the expression of ER stress-related proteins and autophagy-related proteins was confirmed by western blot analysis. The results showed that both ER stress and autophagy were activated in the late luteal phase of the goat CL. To reveal the function of ER stress and autophagy in the CL regression process induced by PGF2α, we used 4-phenyl butyric acid (4-PBA) and chloroquine (CQ) for inhibiting ER stress and autophagy, respectively. Through the apoptotic rate detected by the flow cytometry and the expression of ER stress-and autophagy-related proteins detected by western blotting, we demonstrated that ER stress promoted goat luteal cell apoptosis and autophagy, and that apoptosis can be enhanced by the inhibition of autophagy. In addition, knockdown of EIF2S1, which blocked the PERK pathway activation, promoted apoptosis by reducing autophagy in goat luteal cells treated with PGF2α. In conclusion, our study indicates that ER stress promotes goat luteal cell apoptosis to regulate the regression of CL and activates autophagy to inhibit the goat luteal cell apoptosis via PERK signaling pathway.

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“…Heat stress increases production of proinflammatory cytokines, including tumor necrosis factor α (TNFα) (Chow et al, 1999). Culture of bovine luteal cells in vitro with TNFα increased media concentrations of PGF 2α in a dosedependent manner (Townson and Pate, 1996), and short-term in vitro isolated perfusion culture of bovine ovaries with constant LPS administration increased PGF 2α media concentrations (Lüttgenau et al, 2016b ). Moreover, in vitro culture of porcine luteal tissue after in vivo administration of a PGF 2α analog indicated that luteal tissue itself produced PGF 2α (Diaz et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Heat stress during the luteal phase decreases luteal size but does not affect circulating progesterone in gilts1

Bidne

Romoser

Baumgard

et al. 2019

Journal of Animal Science

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Heat stress (HS) occurs when heat dissipation mechanisms are insufficient to maintain euthermia, and it is associated with seasonal infertility (SI), which manifests as smaller litters, longer wean-to-estrus interval, increased abortions, and reduced conception rates. To understand HS-induced mechanisms underlying SI, crossbred post-pubertal gilts (167 ± 10 kg; n = 14) experienced either thermal neutral (TN, 20 ± 1 °C, n = 7) or cyclical HS (35 ± 1 °C for 12 h and 31.6 °C for 12 h, n = 7) conditions from 2 to 12 d post-estrus (dpe). Estrous cycles were synchronized via altrenogest administration for 14 d, phenotypic manifestation of estrus was observed and gilts were assigned to experimental treatment. Gilts were limit fed 2.7 kg daily with ad libitum water access. Blood was collected at 0, 4, 8, and 12 dpe via jugular venipuncture and animals were humanely euthanized at 12 dpe. The corpora lutea (CL) width were measured via digital calipers on both ovaries, and CL from one ovary were excised, weighed, and protein and steroid abundance analyzed via western blotting and ELISA, respectively. Relative to TN, HS increased (P < 0.01) rectal temperature and respiration rates and reduced (P < 0.01) feed intake. The CL from HS ovaries were reduced in diameter (P < 0.05) and weight (P < 0.01) relative to those from TN animals. No difference (P = 0.38) in CL or serum progesterone concentrations between groups was observed at any time point, though at 12 dpe the serum progesterone:CL weight was increased (P < 0.10) by HS. No treatment differences (P = 0.84) in circulating insulin were observed. Luteal protein abundance of steroid acute regulatory protein, 3 beta-hydroxysteroid, or prostaglandin F2α receptor were not different between treatments (P = 0.73). Taken together, these data demonstrate that the CL mass is HS sensitive, but this phenotype does not appear to be explained by the metrics evaluated herein. Regardless, HS-induced decreased CL size may have important implications to pig SI and warrants additional attention.

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Lipopolysaccharide enhances apoptosis of corpus luteum in isolated perfused bovine ovaries in vitro

Cited by 14 publications

References 63 publications

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum

Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy

Heat stress during the luteal phase decreases luteal size but does not affect circulating progesterone in gilts1

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