Luteal Regression in the Primate: Different Forms of Cell Death During Naturaland Gonadotropin-Releasing Hormone Antagonist or Prostaglandin Analogue-Induced Luteolysis

Fraser, H. M.; Lunn, S. F.; Harrison, David J.; Kerr, Jeffery B

doi:10.1095/biolreprod61.6.1468

Cited by 67 publications

(37 citation statements)

References 37 publications

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“…This contrasts with observations on the characteristic effects of withdrawal of the trophic factor, luteinising hormone (LH), which have been described recently (Fraser et al 1999b, suggesting that anti-VEGF treatment does not markedly interfere with pituitary LH secretion.…”

Section: Discussioncontrasting

confidence: 68%

Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

Dickson

Bicknell²,

Fraser

2001

Journal of Endocrinology

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Vascular endothelial growth factor (VEGF) is essential for the angiogenesis required for the formation of the corpus luteum; however, its role in ongoing luteal angiogenesis and in the maintenance of the established vascular network is unknown. The aim of this study was to determine whether VEGF inhibition could intervene in ongoing luteal angiogenesis using immunoneutralisation of VEGF starting in the mid-luteal phase. In addition, the effects on endothelial cell survival and the recruitment of periendothelial support cells were examined. Treatment with a monoclonal antibody to VEGF, or mouse gamma globulin for control animals, commenced on day 7 after ovulation and continued for 3 days. Bromodeoxyuridine (BrdU), used to label proliferating cells to obtain a proliferation index, was administered one hour before collecting ovaries from control and treated animals. Ovarian sections were stained using antibodies to BrdU, the endothelial cell marker, CD31, the pericyte marker, alpha-smooth muscle actin, and 3 end DNA fragments as a marker for apoptosis. VEGF immunoneutralisation significantly suppressed endothelial cell proliferation and the area occupied by endothelial cells while increasing pericyte coverage and the incidence of endothelial cell apoptosis. Luteal function was markedly compromised by anti-VEGF treatment as judged by a 50% reduction in plasma progesterone concentration. It is concluded that ongoing angiogenesis in the mid-luteal phase is primarily driven by VEGF, and that a proportion of endothelial cells of the mid-luteal phase vasculature are dependent on VEGF support.

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Section: Discussioncontrasting

confidence: 68%

Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

Dickson

Bicknell²,

Fraser

2001

Journal of Endocrinology

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“…Signifi cantly increased occurrence of lipids in cows with BCS1 and BCS2 was found also in our study, which indicates on the involvement of regressive mechanisms. Similar results were obtained also by Fraser et al [15], who found that natural luteolysis in primates was associated with lutein cell atrophy, condensation of cytoplasmic inclusions and organelles and increase in relative volume of lipids.…”

Section: Discussionsupporting

confidence: 90%

Ultrastructural Changes in the Cyclic Corpus Luteum of Dairy Cows with Different Body Condition

et al. 2016

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The aim of the study was to defi ne ultrastructural changes in the ovarian cyclic corpus luteum (CL) of dairy cows with different body condition score (BCS, a 5-point scale). The ovaries were recovered from slaughtered Holstein cows of BCS1 (emaciation; n= 4), BCS2 (tendency to emaciation; n=4), BCS3 (average body condition; n= 4), BCS4 (tendency to fattening; n=4) and BCS5 (fattening; n=4). Average ages of cows were: 6.2, 4.1, 5.7, 5.5 and 6.36 years for BCS1, BCS2, BCS3, BCS4 and BCS5, respectively. For electron microscopy, functioning CL at the mid-luteal phase were fi xed in the aldehyde solution and post-fi xed in 1% OsO4 solution. For lipid visualization the samples were soaked in 1% p-phenylenediamine solution in acetone. Durcupan ultrathin sections (90 nm) were contrasted with uranyl acetate and lead citrate and viewed under Jeol transmission electron microscope. Occurrence of cell organelles was determined by counting the relative volume of individual cellular components using the modifi ed universal test network. Luteal regression of cyclic CL was characterized by atrophy of lutein cells, condensation of organelles and cytoplasmic inclusions, increase in relative volumes of vacuoles, lysosomes, peroxisomes, autophagosomes and lipids. There were signifi cant differences (p<0.05) among BCS1, BCS2, BCS4 and BCS5 cows in the occurrence of lipids, vacuoles, lysosomes and autophagosomes in the lutein cells compared to BCS3 cows. Cows with BCS2 or BCS1 had higher relative volume of lipid droplets, whilst the BCS4 or BCS5 cows had increased occurrence (relative volume) of vacuoles, lysosomes, peroxisomes and autolysosomes. These results show that luteolysis of cyclic CL of cows has different patterns in each BCS group; in the emaciated and fattened cows luteolysis starts earlier than in cows with average body condition.

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“…Progression through the ovarian cycle was determined by monitoring blood progesterone levels and ovaries were obtained during the follicular phase (early, n=3; mid, n=2; late, n=3) and were the same samples as those described by Fraser et al (1999), or during the luteal phase of the non-pregnant cycle and on day 21 of pregnancy. Tissues were fixed by immersion in 4% paraformaldehyde for 24 h and stored in 70% ethanol until processed into paraffin wax as described previously (Millar et al 1993).…”

Section: Tissue Collectionmentioning

confidence: 99%

Development and validation of a new monoclonal antibody to mammalian aromatase

Turner

MacPherson²,

Millar³

et al. 2002

Journal of Endocrinology

112

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The biosynthesis of oestrogens from androgens is catalysed by the aromatase complex, an essential component of which is the aromatase cytochrome P450 (P450 arom) protein. Expression of a functional P450 arom is essential for normal fertility in males and females and the sequence of the protein is highly conserved. We have raised a new monoclonal antibody against a conserved peptide and validated it on fixed tissue sections of the rat, common marmoset (Callthrix jacchus) and human. The monoclonal antibody was used successfully for Western analysis and specifically reacted with a 55 kDa protein in microsomal extracts. On sections of ovaries in all three species, expression in follicles was specific to the mural granulosa cells of antral follicles and was present in corpora lutea. In the human and marmoset, staining of luteal cells was markedly heterogeneous and did not appear to vary consistently with the stage of the cycle. The intensity of immunostaining was elevated in corpora lutea from pregnant rats and following human chorionic gonadotropin rescue in the human. In the testis, the highest levels of expression were observed in the Leydig cells within the interstitium. In adult rat and marmoset, and possibly also in the human, some P450 arom was associated with the cytoplasm surrounding elongate spermatids but other germ cells were immunonegative.In conclusion, a new monoclonal antibody specific for P450 arom recognises the protein in rodent, primate and human. Its ability to work on fixed tissue sections will facilitate identification of individual cells expressing P450 arom within complex tissues.

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Luteal Regression in the Primate: Different Forms of Cell Death During Naturaland Gonadotropin-Releasing Hormone Antagonist or Prostaglandin Analogue-Induced Luteolysis

Cited by 67 publications

References 37 publications

Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

Ultrastructural Changes in the Cyclic Corpus Luteum of Dairy Cows with Different Body Condition

Development and validation of a new monoclonal antibody to mammalian aromatase

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