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Article ; Online: Dynamics of Mitochondrial DNA Copy Number and Membrane Potential in Mouse Pre-Implantation Embryos: Responses to Diverse Types of Oxidative Stress.

Winstanley, Yasmyn E / Liu, Jun / Adhikari, Deepak / Gonzalez, Macarena B / Russell, Darryl L / Carroll, John / Robker, Rebecca L

Genes

2024 Volume 15, Issue 3

Abstract: Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their ... ...

Abstract	Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O
MeSH term(s)	Animals ; Mice ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; DNA Copy Number Variations/genetics ; Membrane Potentials ; Mitochondria/metabolism ; Oxidative Stress/genetics ; Embryonic Development/genetics ; Oxygen/metabolism
Chemical Substances	DNA, Mitochondrial ; Oxygen (S88TT14065)
Language	English
Publishing date	2024-03-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes15030367
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Article ; Online: Clomiphene citrate administered in peri-conception phase causes fetal loss and developmental impairment in mice.

Chin, Peck Y / Kieffer, Tom E C / Prins, Jelmer R / Russell, Darryl L / Davies, Michael J / Robertson, Sarah A

Endocrinology

2024

Abstract: Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this ... ...

Abstract	Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated in mice the consequences for fetal development and pregnancy outcome of peri-conception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 h after mating was seen, with a moderate dose of 0.75 mg/kg sufficient to cause altered reproductive outcomes in three independent cohorts. Viable pregnancy was reduced by 30%, late gestation fetal weight was reduced by 16%, and ∼30% of fetuses exhibited delayed development and/or congenital abnormalities not seen in control dams, including defects of the lung, kidney, liver, eye, skin, limbs, and umbilicus. Clomiphene citrate also caused a 30 h average delay in time of birth, and elevated rate of pup death in the early postnatal phase. In surviving offspring, growth trajectory tracking and body morphometry analysis at 20 weeks of age showed post-weaning growth and development comparable to controls. A dysregulated inflammatory response in the endometrium was observed and may contribute to the underlying pathophysiological mechanism. These results demonstrate that in utero exposure to clomiphene citrate during early pregnancy can inhibit implantation and impact fetal growth and development, causing adverse perinatal outcomes. The findings raise the prospect of similar iatrogenic effects in women where clomiphene citrate may be present in the peri-conception phase unless its use is well-supervised.
Language	English
Publishing date	2024-04-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqae047
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Article: Dynamic regulation of semaphorin 7A and adhesion receptors in ovarian follicle remodeling and ovulation.

Emery, Alaknanda / Dunning, Kylie R / Dinh, Doan T / Akison, Lisa K / Robker, Rebecca L / Russell, Darryl L

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1261038

Abstract: The ovarian follicle is a complex structure that protects and helps in the maturation of the oocyte, and then releases it through the controlled molecular and structural remodeling process of ovulation. The progesterone receptor (PGR) has been shown to ... ...

Abstract	The ovarian follicle is a complex structure that protects and helps in the maturation of the oocyte, and then releases it through the controlled molecular and structural remodeling process of ovulation. The progesterone receptor (PGR) has been shown to be essential in regulating ovulation-related gene expression changes. In this study, we found disrupted expression of the cellular adhesion receptor gene
Language	English
Publishing date	2023-10-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1261038
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Article ; Online: A Primate-Specific Mediator of Ovulation?

Robker, Rebecca L / Russell, Darryl L

Endocrinology

2016 Volume 157, Issue 11, Page(s) 4209–4211

Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2016-1706
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Article ; Online: NanoFIRE: A NanoLuciferase and Fluorescent Integrated Reporter Element for Robust and Sensitive Investigation of HIF and Other Signalling Pathways.

Roennfeldt, Alison E / Allen, Timothy P / Trowbridge, Brooke N / Beard, Michael R / Whitelaw, Murray L / Russell, Darryl L / Bersten, David C / Peet, Daniel J

Biomolecules

2023 Volume 13, Issue 10

Abstract: The Hypoxia Inducible Factor (HIF) transcription factors are imperative for cell adaption to low oxygen conditions and development; however, they also contribute to ischaemic disease and cancer. To identify novel genetic regulators which target the HIF ... ...

Abstract	The Hypoxia Inducible Factor (HIF) transcription factors are imperative for cell adaption to low oxygen conditions and development; however, they also contribute to ischaemic disease and cancer. To identify novel genetic regulators which target the HIF pathway or small molecules for therapeutic use, cell-based reporter systems are commonly used. Here, we present a new, highly sensitive and versatile reporter system, NanoFIRE: a NanoLuciferase and Fluorescent Integrated Reporter Element. Under the control of a Hypoxic Response Element (HRE-NanoFIRE), this system is a robust sensor of HIF activity within cells and potently responds to both hypoxia and chemical inducers of the HIF pathway in a highly reproducible and sensitive manner, consistently achieving 20 to 150-fold induction across different cell types and a Z' score > 0.5. We demonstrate that the NanoFIRE system is adaptable via substitution of the response element controlling NanoLuciferase and show that it can report on the activity of the transcriptional regulator Factor Inhibiting HIF, and an unrelated transcription factor, the Progesterone Receptor. Furthermore, the lentivirus-mediated stable integration of NanoFIRE highlights the versatility of this system across a wide range of cell types, including primary cells. Together, these findings demonstrate that NanoFIRE is a robust reporter system for the investigation of HIF and other transcription factor-mediated signalling pathways in cells, with applications in high throughput screening for the identification of novel small molecule and genetic regulators.
MeSH term(s)	Humans ; Transcription Factors/genetics ; Gene Expression Regulation ; Response Elements ; Nuclear Proteins/genetics ; Hypoxia/genetics ; Cell Hypoxia/genetics
Chemical Substances	Transcription Factors ; Nuclear Proteins
Language	English
Publishing date	2023-10-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom13101545
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Article ; Online: Riding the wave: determining the hierarchy of ovarian follicle activation.

Russell, Darryl L / Rodgers, Raymond J

Biology of reproduction

2015 Volume 93, Issue 4, Page(s) 99

MeSH term(s)	Animals ; Female ; Ovarian Follicle/embryology ; Ovary/embryology ; Pregnancy
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1095/biolreprod.115.134932
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Zs.A 551: Show issues

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Article ; Online: Progesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling.

Dinh, Doan T / Breen, James / Nicol, Barbara / Foot, Natalie J / Bersten, David C / Emery, Alaknanda / Smith, Kirsten M / Wong, Ying Y / Barry, Simon C / Yao, Humphrey H C / Robker, Rebecca L / Russell, Darryl L

Nucleic acids research

2023 Volume 51, Issue 12, Page(s) 5981–5996

Abstract: Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that ...

Abstract	Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.
MeSH term(s)	Animals ; Female ; Mice ; Chromatin/genetics ; Chromatin Assembly and Disassembly/genetics ; Gene Expression Regulation ; Mammals/genetics ; Mice, Knockout ; Receptors, Progesterone/genetics ; Receptors, Progesterone/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Core Binding Factor Alpha 2 Subunit/metabolism ; Transcription, Genetic
Chemical Substances	Chromatin ; Receptors, Progesterone ; Transcription Factors ; Runx1 protein, mouse ; Core Binding Factor Alpha 2 Subunit
Language	English
Publishing date	2023-04-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad271
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Zs.A 1067: Show issues

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Article ; Online: Coordination of Ovulation and Oocyte Maturation: A Good Egg at the Right Time.

Robker, Rebecca L / Hennebold, Jon D / Russell, Darryl L

Endocrinology

2018 Volume 159, Issue 9, Page(s) 3209–3218

Abstract: Ovulation is the appropriately timed release of a mature, developmentally competent oocyte from the ovary into the oviduct, where fertilization occurs. Importantly, ovulation is tightly linked with oocyte maturation, demonstrating the interdependency of ... ...

Abstract	Ovulation is the appropriately timed release of a mature, developmentally competent oocyte from the ovary into the oviduct, where fertilization occurs. Importantly, ovulation is tightly linked with oocyte maturation, demonstrating the interdependency of these two parallel processes, both essential for female fertility. Initiated by pituitary gonadotropins, the ovulatory process is mediated by intrafollicular paracrine factors from the theca, mural, and cumulus granulosa cells, as well as the oocyte itself. The result is the induction of cumulus expansion, proteolysis, angiogenesis, inflammation, and smooth muscle contraction, which are each required for follicular rupture. These complex intercellular communication networks and the essential ovulatory genes have been well defined in mouse models and are highly conserved in primates, including humans. Importantly, recent discoveries in regulation of ovulation highlight new areas of investigation.
MeSH term(s)	Animals ; Cumulus Cells/physiology ; Female ; Follicle Stimulating Hormone/metabolism ; Follicle Stimulating Hormone/physiology ; Humans ; Luteinizing Hormone/metabolism ; Luteinizing Hormone/physiology ; Mice ; Muscle Contraction/physiology ; Muscle, Smooth ; Neovascularization, Physiologic/physiology ; Oocytes/growth & development ; Oocytes/metabolism ; Ovarian Follicle/physiology ; Ovulation/metabolism ; Ovulation/physiology ; Primates ; Proteolysis ; Theca Cells/physiology ; Time Factors
Chemical Substances	Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2018-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2018-00485
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Article ; Online: ADAMTS1 Promotes Adhesion to Extracellular Matrix Proteins and Predicts Prognosis in Early Stage Breast Cancer Patients.

Tan, Izza A / Frewin, Kate / Ricciardelli, Carmela / Russell, Darryl L

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2019 Volume 52, Issue 6, Page(s) 1553–1568

Abstract: Background/aims: Despite, several studies demonstrating pro-metastatic effects of the metalloproteinase ADAMTS1 in breast cancer, its role in facilitating the metastatic cascade remains unclear. To date there have been limited studies that have examined ...

Abstract	Background/aims: Despite, several studies demonstrating pro-metastatic effects of the metalloproteinase ADAMTS1 in breast cancer, its role in facilitating the metastatic cascade remains unclear. To date there have been limited studies that have examined the expression of ADAMTS1 in primary and metastatic breast cancer tissues. Methods: We assessed ADAMTS1 mRNA levels in publically available breast cancer sets and analysed ADAMTS1 protein levels by immunohistochemistry in breast tissue microarrays containing normal breast tissue (n=9), primary invasive ductal breast carcinomas (n=79) and metastatic lesions (n=58). To understand the underlying events influenced by ADAMTS1 and provide a mechanism by which tumors expressing this protease promote metastasis, we assessed the ability of PyMT/Adamts1+/+, PyMT/Adamts1+/- and PyMT/Adamts1-/- primary mammary cancer cells to adhere to matrigel and migrate or invade towards a chemoattractive environment. Results: High ADAMTS1 expression was associated with reduced disease-free survival, distant metastasis free-survival and overall survival in breast cancer patients with node negative disease. Although ADAMTS1 expression was reduced in primary breast cancers compared to normal tissue and not elevated in metastatic lesions, high ADAMTS1 immunostaining was associated with a higher number of positive lymph nodes (p=0.006) and the presence of distant metastasis (p=0.023). Depletion of Adamts1 in mammary cancer cells impeded their adhesion to a biological matrix substratum and diminished cell migration but not invasion. Conclusion: The effects observed on cell adhesion and migration demonstrates a potential mechanism whereby ADAMTS1 promotes breast cancer metastasis.
MeSH term(s)	ADAMTS1 Protein/genetics ; ADAMTS1 Protein/metabolism ; Animals ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Disease-Free Survival ; Extracellular Matrix Proteins/metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mice ; Mice, Transgenic ; Neoplasm Staging ; Prognosis
Chemical Substances	Extracellular Matrix Proteins ; ADAMTS1 Protein (EC 3.4.24.-) ; ADAMTS1 protein, human (EC 3.4.24.-)
Language	English
Publishing date	2019-05-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.33594/000000108
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Zs.A 3160: Show issues

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Article ; Online: Dietary intake and cardiovascular outcomes in patients with chronic vascular disease: insights from the COMPASS trial cohort.

Wan, Darryl / Dehghan, Mahshid / de Souza, Russell J / Ramasundarahettige, Chinthanie / Eikelboom, John W / Bosch, Jackie / Maggioni, Aldo P / Bhatt, Deepak L / Yusuf, Salim / Anand, Sonia S

European journal of preventive cardiology

2023 Volume 30, Issue 8, Page(s) 709–718

Abstract: Aims: Patients with coronary artery disease (CAD) and patients with peripheral artery disease (PAD) are at risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There are limited data regarding dietary patterns and ... ...

Abstract	Aims: Patients with coronary artery disease (CAD) and patients with peripheral artery disease (PAD) are at risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There are limited data regarding dietary patterns and the risk of recurrent MACE and MALE in CAD and PAD patients. We aimed to identify dietary patterns associated with MACE and MALE in patients with CAD and/or PAD. Methods and results: We analysed data collected from patients enrolled into the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, in which diet was assessed by a short food frequency questionnaire (FFQ) at baseline. Two dietary pattern scores, the modified Alternate Healthy Eating Index (mAHEI) and Mediterranean Diet Score (mMDS), were calculated. We tested the association between mAHEI and mMDS and the incidence of MACE and/or MALE. The mean mAHEI score was 23.0 ± 7.7 (out of 70) overall and was similar comparing CAD and PAD patients. The incidence of MACE or MALE was 6.3% in the lowest diet quality quartile (as assessed by mAHEI) compared with 4.2% in the highest quartile over 30 months. In the fully adjusted model, the hazard ratio of a low diet quality (Quartile 1) compared with the highest (Quartile 4) for MACE or MALE was 1.27 (95% CI: 1.08-1.49; P = 0.004, Q1 vs. Q4). This excess hazard was primarily driven by higher MACE in both the CAD and PAD cohorts. Conclusions: Poor diet quality as assessed by the mAHEI is independently associated with a higher risk of recurrent MACE and MALE in patients with chronic CAD and/or PAD.
MeSH term(s)	Humans ; Coronary Artery Disease/diagnosis ; Coronary Artery Disease/epidemiology ; Coronary Artery Disease/complications ; Cardiovascular System ; Peripheral Arterial Disease/diagnosis ; Peripheral Arterial Disease/epidemiology ; Peripheral Arterial Disease/complications ; Risk Factors ; Eating
Language	English
Publishing date	2023-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2626011-6
ISSN	2047-4881 ; 2047-4873
ISSN (online)	2047-4881
ISSN	2047-4873
DOI	10.1093/eurjpc/zwad062
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Zs.A 4686: Show issues

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