Effects of sustained hyperprolactinemia in late gestation on mammary development of gilts

Caron, Annie; Palin, Marie‐France; Hovey, Russell C.; Cohen, Julia R; Laforest, Jean-Paul; Farmer, C.

doi:10.1016/j.domaniend.2019.106408

Cited by 9 publications

(15 citation statements)

References 37 publications

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“…For the qPCR analysis of selected DEGs in mammary parenchymal tissue, maintaining high circulating concentrations of prolactin for 20 days provoked more alterations in mRNA abundance (T20 vs CTL) compared with a shorter treatment period (T7 vs CTL). The limited effect of domperidone after 7 days of treatment was expected since T7 and CTL gilts had similar mammary composition variables [ 6 ]. On the other hand, the important downregulation (4 to 15 fold changes) of CAMK1G , COL9A1 , P2RX7 and TDRD1 mRNA abundance (this study) and the higher parenchyma involution score in T7 than CTL gilts [ 6 ] suggest that the involution process is already initiated after 7 days of domperidone treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The limited effect of domperidone after 7 days of treatment was expected since T7 and CTL gilts had similar mammary composition variables [ 6 ]. On the other hand, the important downregulation (4 to 15 fold changes) of CAMK1G , COL9A1 , P2RX7 and TDRD1 mRNA abundance (this study) and the higher parenchyma involution score in T7 than CTL gilts [ 6 ] suggest that the involution process is already initiated after 7 days of domperidone treatment.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the study of VanKlompenberg et al [ 5 ] reported that provision of domperidone, a dopamine receptor antagonist known to induce hyperprolactinemia, to late-gestating gilts increased PRL concentrations from days 90 to 97 of gestation and stimulated mammary epithelial cells (MEC) differentiation before farrowing, with a subsequent increase in milk production and piglet growth. In a recent study, we demonstrated that maintaining a sustained hyperprolactinemia throughout the end of gestation in gilts had a negative effect on mammary development [ 6 ]. This was evidenced by lower mammary RNA, DNA and protein contents, early involution of mammary parenchymal tissue and lower mRNA abundance of the prolactin receptor ( PRLR ) gene in parenchyma from gilts treated with domperidone for 20 days (T20, from d 90 to 109 of gestation) when compared with controls (CTL) or gilts treated for 7 days (T7, from d 90 to 96) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, we demonstrated that maintaining a sustained hyperprolactinemia throughout the end of gestation in gilts had a negative effect on mammary development [ 6 ]. This was evidenced by lower mammary RNA, DNA and protein contents, early involution of mammary parenchymal tissue and lower mRNA abundance of the prolactin receptor ( PRLR ) gene in parenchyma from gilts treated with domperidone for 20 days (T20, from d 90 to 109 of gestation) when compared with controls (CTL) or gilts treated for 7 days (T7, from d 90 to 96) [ 6 ]. The T20-treated gilts experienced premature milk synthesis and secretion, which likely led to premature mammary involution in the absence of suckling piglets [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…This was evidenced by lower mammary RNA, DNA and protein contents, early involution of mammary parenchymal tissue and lower mRNA abundance of the prolactin receptor ( PRLR ) gene in parenchyma from gilts treated with domperidone for 20 days (T20, from d 90 to 109 of gestation) when compared with controls (CTL) or gilts treated for 7 days (T7, from d 90 to 96) [ 6 ]. The T20-treated gilts experienced premature milk synthesis and secretion, which likely led to premature mammary involution in the absence of suckling piglets [ 6 ]. Such an effect has been observed by Quaglino et al [ 7 ] who reported that milk stasis can cause mechanical stretch to MECs, which can in turn initiate the activation or inhibition of multiple signaling pathways known to provoke cell death.…”

Section: Introductionmentioning

confidence: 99%

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Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts

2023

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Background Gilts experiencing sustained hyperprolactinemia from d 90 to 109 of gestation showed an early onset of lactogenesis coupled with premature mammary involution. To better understand the molecular mechanisms underlying the premature mammary involution observed in these gilts, a transcriptomic analysis was undertaken. Therefore, this study aimed to explore the effect of hyperprolactinemia on the global transcriptome in the mammary tissue of late gestating gilts and identify the molecular pathways involved in triggering premature mammary involution. Methods On d 90 of gestation, gilts received daily injections of (1) canola oil until d 109 ± 1 of gestation (CTL, n = 18); (2) domperidone (to induce hyperprolactinemia) until d 96 ± 1 of gestation (T7, n = 17) or; (3) domperidone (until d 109 ± 1 of gestation (T20, n = 17). Mammary tissue was collected on d 110 of gestation and total RNA was isolated from six CTL and six T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array was used for hybridization. Functional enrichment analyses were performed to explore the biological significance of differentially expressed genes, using the DAVID bioinformatics resource. Results The expression of 335 genes was up-regulated and that of 505 genes down-regulated in the mammary tissue of T20 vs CTL gilts. Biological process GO terms and KEGG pathways enriched in T20 vs CTL gilts reflected the concurrent premature lactogenesis and mammary involution. When looking at individual genes, it appears that mammary cells from T20 gilts can simultaneously upregulate the transcription of milk proteins such as WAP, CSN1S2 and LALBA, and genes triggering mammary involution such as STAT3, OSMR and IL6R. The down-regulation of PRLR expression and up-regulation of genes known to inactivate the JAK-STAT5 pathway (CISH, PTPN6) suggest the presence of a negative feedback loop trying to counteract the effects of hyperprolactinemia. Conclusions Genes and pathways identified in this study suggest that sustained hyperprolactinemia during late-pregnancy, in the absence of suckling piglets, sends conflicting pro-survival and cell death signals to mammary epithelial cells. Reception of these signals results in a mammary gland that can simultaneously synthesize milk proteins and initiate mammary involution.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts

2023

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Reproductive health of the sow during puerperium

Björkman

Kauffold

Kaiser

2022

Molecular Reproduction Devel

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The modern hyperprolific sow is susceptible to metabolic disease and chronic inflammation. The most sensitive phase is parturition, when the sow experiences systemic inflammation and stress, and major changes in metabolism and endocrinology. Resolution of inflammation and stress needs to happen quickly to ensure good reproductive health during puerperium. If the sow fails to adapt to these changes, puerperal disease may occur. The economically most important puerperal disease complex is the postpartum dysgalactia syndrome (PPDS). Other puerperal diseases include infections of the urogenital tract. Diagnosis of PPDS and urogenital disease on‐farm is challenging but several diagnostic methods, including clinical examination, behavioral observations, ultrasonography and biomarkers are available. Ultrasonography is an excellent tool for monitoring the health of the urogenital tract, the mammary gland, and uterine involution and guide further diagnostic interventions. Biomarkers such as Chromogranin A, tumor necrosis factor‐α, and interleukin‐6 represent promising tools to monitor general health and the systemic state of inflammation and oxidative stress of the sow. Nonsteroidal anti‐inflammatory drugs, dopamine antagonists, and oxytocin are promising to address the symptoms of PPDS. Reducing of stress, improving nutrition and intestinal health, and supporting animal welfare‐friendly husbandry help in the prevention of PPDS.

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Intramammary Labeling of Epithelial Cell Division

Machiela,

Hovey

2024

J Mammary Gland Biol Neoplasia

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Thymidine analogs such as ethynyl deoxyuridine (EdU) or bromodeoxyuridine (BrdU) can be used to label mitosis of mammary epithelial cells (MEC) and to quantify their proliferation. However, labeling cells in larger animals requires considerable amounts of chemical that can be costly and hazardous. We developed a strategy to infuse EdU into the mammary glands of ewes to directly label mitotic MEC. First, each udder half of nulliparous ewes (n = 2) received an intramammary infusion of one of four different concentrations of EdU (0, 0.1, 1.0 or 10 mM) which was compared to BrdU IV (5 mg/kg) 24 h later. Tissues were analyzed by immunofluorescent histochemistry to detect EdU, BrdU, and total MEC. Of the EdU doses tested, 10 mM EdU yielded the greatest labeling index, while a proportion of MEC were labeled by both EdU and BrdU. We next sought to establish whether intramammary labeling could detect the induction of mitosis after exposure to exogenous estrogen and progesterone (E + P). We first infused EdU (10 mM) into the right udder half of ewes (n = 6) at t 0, followed by thymidine (100 mM) 24 h later to prevent further labeling. Three ewes were then administered E + P for 5 d, while n = 3 ewes served as controls. On d 5, EdU was infused into the left udder half of all mammary glands alongside BrdU IV (5 mg/kg). By the time of necropsy 24 h later an average MEC labeling index of 2.9% resulted from EdU delivered at t 0. In the left half of the udder on d 5, CON glands had a final EdU labeling index of 3.4% while glands exposed to E + P had a labeling index of 4.6% (p = 0.05). The corresponding degree of labeling with BrdU was 5.6% in CON glands, and 12% following E + P (p < 0.001). Our findings reveal that intramammary labeling is an efficient and cost-effective method for single- and dual-labeling of cell division in the mammary glands.

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Effects of sustained hyperprolactinemia in late gestation on mammary development of gilts

Cited by 9 publications

References 37 publications

Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts

Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts

Reproductive health of the sow during puerperium

Intramammary Labeling of Epithelial Cell Division

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