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CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation.

ABSTRACT: Adequate corpus luteum (CL) function is paramount to successful pregnancy. Structural and functional CL integrity is controlled by diverse cell types that contribute and respond to the local cytokine milieu. The chemokine ligand 12 (CXCL12) and receptor, CXCR4, are modulators of inflammation and cell survival, but little is understood about CXCL12-CXCR4 axis and CL functional regulation. Corpora lutea from control nonpregnant ewes (n = 5; day 10 estrous cycle (D10C)) and pregnant ewes (n = 5/day) on days 20 (D20P) and 30 (D30P) post-breeding were analyzed for gene and protein expression of CXCL12, CXCR4, and select inflammatory cytokines. In separate cell culture studies, cytokine production was evaluated following CXCL12 treatment. Abundance of CXCL12 and CXCR4 increased (P < 0.05) in pregnant ewes compared to nonpregnant ewes, as determined by a combination of quantitative PCR, immunoblot, and immunofluorescence microscopy. CXCR4 was detected in steroidogenic and nonsteroidogenic cells in ovine CL, and select pro-inflammatory mediators were greater in CL from pregnant ewes. In vitro studies revealed greater abundance of tumor necrosis factor (TNF) following CXCL12 administration (P = 0.05), while P4 levels in cell media were unchanged. Fully functional CL of pregnant ewes is characterized by increased abundance of inflammatory cytokines which may function in a luteotropic manner. We report concurrent increases in CXCL12, CXCR4, and select inflammatory mediators in ovine CL as early pregnancy progresses. We propose CXCL12 stimulates production of select cytokines, rather than P4 in the CL to assist in CL establishment and survival.

SUBMITTER: McIntosh SZ

PROVIDER: S-EPMC8677687 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Macrophages regulate corpus luteum development during embryo implantation in mice.

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| S-EPMC3726148 | biostudies-literature

Pregnancy-associated genes contribute to antiluteolytic mechanisms in ovine corpus luteum.

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Autophagy Attenuation Hampers Progesterone Synthesis during the Development of Pregnant Corpus Luteum.

Project description:The contribution of autophagy to catabolic balance has been well-established in various types of cells, whereas the involvement of autophagy in progesterone synthesis during rat pregnancy still remains unknown. Therefore, the present study was designed to evaluate the role of autophagy in progesterone production during the luteal development of pregnant rats. The results showed autophagy-related proteins was maintained at a low level on day 10 after pregnancy, significantly induced on day 16 and subsided to a relative low level on day 21, which was consistent with the changes of serum progesterone levels. The findings further indicated the contribution of autophagy to progesterone production was regulated by inactivation of Akt/mTOR signaling during the luteal development of pregnant rats in in vivo and in vitro experiments. Further investigations revealed autophagy may be involved in the surge of progesterone production in pregnant rats, as inhibition of autophagy by 3-MA compromised serum progesterone levels. Furthermore, 3-MA treatment also leveled down the number of lipid droplets in luteal cells, implying that autophagy may affect the production of progesterone by manipulating the formation of lipid droplets in luteal cells. In addition, the results suggested that mitophagy was mobilized during the primary stage of luteolysis and inhibition of autophagy promoted the increase of redundant mitochondrial and cytoplasmic cytochrome C in luteal cells of pregnant rats. Taken together, the present study indicated that autophagy-related proteins were induced by the inactivation of Akt/mTOR signaling and then contributed to the progesterone production possibly by affecting the formation of intracellular lipid droplets during the luteal development of pregnant rats. To our knowledge, this will provide a new insight into the important mechanism of autophagy regulating progesterone production in ovaries of pregnant mammals.

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Temporal changes in the corpus luteum during early pregnancy

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-03-28 | GSE147631 | GEO

Genomic profiling of bovine corpus luteum maturation.

Project description:To unveil novel global changes associated with corpus luteum (CL) maturation, we analyzed transcriptome data for the bovine CL on days 4 and 11, representing the developing vs. mature gland. Our analyses revealed 681 differentially expressed genes (363 and 318 on day 4 and 11, respectively), with ?2 fold change and FDR of <5%. Different gene ontology (GO) categories were represented prominently in transcriptome data at these stages (e.g. days 4: cell cycle, chromosome, DNA metabolic process and replication and on day 11: immune response; lipid metabolic process and complement activation). Based on bioinformatic analyses, select genes expression in day 4 and 11 CL was validated with quantitative real-time PCR. Cell specific expression was also determined in enriched luteal endothelial and steroidogenic cells. Genes related to the angiogenic process such as NOS3, which maintains dilated vessels and MMP9, matrix degrading enzyme, were higher on day 4. Importantly, our data suggests day 11 CL acquire mechanisms to prevent blood vessel sprouting and promote their maturation by expressing NOTCH4 and JAG1, greatly enriched in luteal endothelial cells. Another endothelial specific gene, CD300LG, was identified here in the CL for the first time. CD300LG is an adhesion molecule enabling lymphocyte migration, its higher levels at mid cycle are expected to support the transmigration of immune cells into the CL at this stage. Together with steroidogenic genes, most of the genes regulating de-novo cholesterol biosynthetic pathway (e.g HMGCS, HMGCR) and cholesterol uptake from plasma (LDLR, APOD and APOE) were upregulated in the mature CL. These findings provide new insight of the processes involved in CL maturation including blood vessel growth and stabilization, leucocyte transmigration as well as progesterone synthesis as the CL matures.

| S-EPMC5874041 | biostudies-literature

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BNIP3 expression in bovine follicle and corpus luteum.

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| S-EPMC5836779 | biostudies-literature

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