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Is There a Genetic Predisposition to Postoperative Adhesion Development?

Thakur, Mili; Rambhatla, Anupama; Qadri, Farnoosh; Chatzicharalampous, Charalampos; Awonuga, Modupe; Saed, Ghassan; Diamond, Michael P; Awonuga, Awoniyi O
Adhesions are permanent fibrovascular bands between peritoneal surfaces, which develop following virtually all body cavity surgeries. The susceptibility to develop, and the severity, of adhesions following intra-abdominal surgery varies within and between individuals, suggesting that heritable factors influence adhesion development. In this manuscript, we discuss the pathophysiology of adhesion development from the perspective of genetic susceptibility. We restrict our discussion to genes and single-nucleotide polymorphisms (SNPs) that are specifically involved in, or that cause modification of, the adhesion development process. We performed a literature search using the PubMed database for all relevant English language articles up to March 2020 (n = 186). We identified and carefully reviewed all relevant articles addressing genetic mutations or single-nucleotide polymorphisms (SNPs) that impact the risk for adhesion development. We also reviewed references from these articles for additional information. We found several reported SNPs, genetic mutations, and upregulation of messenger RNAs that directly or indirectly increase the propensity for postoperative adhesion development, namely in genes for transforming growth factor beta, vascular endothelial growth factor, interferon-gamma, matrix metalloproteinase, plasminogen activator inhibitor-1, and the interleukins. An understanding of genetic variants could provide insight into the pathophysiology of adhesion development. The information presented in this review contributes to a greater understanding of adhesion development at the genetic level and may allow modification of these genetic risks, which may subsequently guide management in preventing and treating this challenging complication of abdominal surgery. In particular, the information could help identify patients at greater risk for adhesion development, which would make them candidates for anti-adhesion prophylaxis. Currently, agents to reduce postoperative adhesion development exist, and in the future, development of agents, which specifically target individual genetic profile, would be more specific in preventing intraperitoneal adhesion development.
PMCID:7579853
PMID: 33090376
ISSN: 1933-7205
CID: 4642412

A genetic association study of kisspeptin 1/ neurokinin B systems in patients with infertility: is it that simple? [Editorial]

Chatzicharalampous, Charalampos
PMID: 32868106
ISSN: 1556-5653
CID: 4582952

Glyphosate Induces Metaphase II Oocyte Deterioration and Embryo Damage by Zinc Depletion and Overproduction of Reactive Oxygen Species

Yahfoufi, Zeina A; Bai, David; Khan, Sana N; Chatzicharalampous, Charalampos; Kohan-Ghadr, Hamid-Reza; Morris, Robert T; Abu-Soud, Husam M
Glyphosate is the most popular herbicide used in modern agriculture, and its use has been increasing substantially since its introduction. Accordingly, glyphosate exposure from food and water, the environment, and accidental and occupational venues has also increased. Recent studies have demonstrated a relationship between glyphosate exposure and a number of disorders such as cancer, immune and metabolic disorders, endocrine disruption, imbalance of intestinal flora, cardiovascular disease, and infertility; these results have given glyphosate a considerable amount of media and scientific attention. Notably, glyphosate is a powerful metal chelator, which could help explain some of its effects. Recently, our findings on 2,3-dimercapto-1-propanesulfonic acid, another metal chelator, showed deterioration of oocyte quality. Here, to generalize, we investigated the effects of glyphosate (0 - 300 μM) on metaphase II mouse oocyte quality and embryo damage to obtain insight on its mechanisms of cellular action and the tolerance of oocytes and embryos towards this chemical. Our work shows for the first time that glyphosate exposure impairs metaphase II mouse oocyte quality via two mechanisms: 1) disruption of the microtubule organizing center and chromosomes such as anomalous pericentrin formation, spindle fiber destruction and disappearance, and defective chromosomal alignment and 2) substantial depletion of intracellular zinc bioavailability and enhancement of reactive oxygen species accumulation. Similar effects were found in embryos. These results may help clarify the effects of glyphosate exposure on female fertility and provide counseling and preventative steps for excessive glyphosate intake and resulting oxidative stress and reduced zinc bioavailability.
PMID: 32315717
ISSN: 1879-3185
CID: 4397002

Hypochlorous acid reversibly inhibits caspase-3: a potential regulator of apoptosis

Jeelani, Roohi; Chatzicharalampous, Charalampos; Kohan-Ghadr, Hamid-Reza; Bai, David; Morris, Robert T; Sliskovic, Inga; Awonuga, Awoniyi; Abu-Soud, Husam M
Caspase-3 is involved in apoptosis. Here, we examine whether hypochlorous acid (HOCl), a final product of myeloperoxidase (MPO), is a modulator of caspase-3 at relatively low concentrations and also its application on metaphase II mouse oocytes. We utilised caspase-3 activity assay, TUNEL assay, the CellEvent caspase 3/7 fluorescent assay, and the MPO/hydrogen peroxide (H2O2) system on mouse oocytes with and without cumulus cells to examine whether low concentrations of HOCl mediate apoptosis by inhibition of caspase-3. A UV-visible spectrophotometer was used to study caspase-3 activity. To determine whether HOCl mediates apoptosis in mouse oocytes, two different concentrations (10 and 100 µM) of HOCl generated by the MPO/H2O2 system were used as treatments (10 µM had little effect on oocyte quality, while 100 µM showed significant deterioration). Induction of apoptotic cell death was determined by TUNEL Assay and the CellEvent caspase 3/7. HOCl mediates caspase-3 inactivation in a dose dependent manner. Subsequent addition of dithiothreitol caused recovery of caspase-3 activity indicating involvement of the oxidation of the Cys-thiol group. Accumulation of HOCl generated by MPO in the presence of caspase-3 also inhibits MPO but requires higher HOCl concentrations, indicating specificity of lower HOCl concentrations to inhibition of caspase-3. Exposure of oocytes to lower HOCl concentrations generated by MPO-H2O2 system prevents MPO-mediated apoptosis whereas exposure to higher HOCl (100 µM) showed apoptosis. Similar results were observed by using the CellEvent caspase 3/7 assay. Low concentrations of HOCl inhibit caspase-3 activity, and may play a role in regulating apoptosis, thus affecting oocyte quality.HighlightsCaspase-3 is involved in apoptosis pathway and loss of this regulation is seen in several diseases.These conditions are associated with inflammation and higher myeloperoxidase (MPO) activity.We examined whether hypochlorous acid (HOCl), generated by MPO, is a modulator of caspase-3.Caspase-3 activity showed a dose dependent decrease with HOCl and this reaction was reversible.HOCl modulates caspase-3 activity and may play a physiological role in regulating apoptosis.
PMID: 31909639
ISSN: 1029-2470
CID: 4258292

Successful Oocyte Retrieval, Fertilization, and Clinical Pregnancy with Low Serum β-hCG on the Day of Oocyte Collection: A Reappraisal of the Definition of the Empty Follicle Syndrome [Case Report]

Van De Velde, Nicole A; Chatzicharalampous, Charalampos; Awonuga, Awoniyi O
Objective/UNASSIGNED:-hCG level, twelve hours after ovulation trigger. Design/UNASSIGNED:. Successful oocyte retrieval. Results/UNASSIGNED:Fourteen oocytes were retrieved of which twelve were in metaphase II and nine fertilized after intracytoplasmic sperm injection (ICSI). Of these, eight embryos survived to day 5 and were subjected to preimplantation genetic screening (PGS) by comparative genomic hybridization (CGH). Results were available the next day, three of the embryos were euploid and one was transferred on day 6. Pregnancy was confirmed twelve days later and currently the patient has an ongoing singleton intrauterine pregnancy. Conclusion/UNASSIGNED:Reproductive Endocrinology and Infertility specialists should be aware that final oocyte maturation could occur following injection of a lower dose of hCG with excellent fertilization rate and embryo development.
PMCID:7031730
PMID: 32089920
ISSN: 2090-6684
CID: 4323042

Catalase prevents myeloperoxidase self-destruction in response to oxidative stress

Ali, Iyad; Khan, Sana N; Chatzicharalampous, Charalampos; Bai, David; Abu-Soud, Husam M
Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxemic respiratory failure. However, information regarding the interrelationship and competition between the two enzymes, free iron accumulation, and decreased levels of non-enzymatic antioxidants at sites of inflammation is still lacking. Myeloperoxidase catalyzes the generation of hypochlorous acid (HOCl) from the reaction of hydrogen peroxide (H2O2) and chloride (Cl-). Self-generated HOCl has recently been proposed to auto-inhibit MPO through a mechanism that involves MPO heme destruction. Here, we investigate the interplay of MPO, HOCl, and CAT during catalysis, and explore the crucial role of MPO inhibitors and HOCl scavengers in protecting the catalytic site from protein modification of both enzymes against oxidative damage mediated by HOCl. We showed that CAT not only competes with MPO for H2O2 but also scavenges HOCl. The protective role provided by CAT versus the damaging effect provided by HOCl depends in part on the ratio between MPO/CAT and the affinity of the enzymes towards H2O2 versus HOCl. The severity of such damaging effects mainly depends on the ratio of HOCl to enzyme heme content. In addition to its effect in mediating protein modification and aggregation, HOCl oxidatively destroys the catalytic sites of the enzymes, which contain porphyrin rings and iron. Thus, modulation of MPO/CAT activities may be a fundamental feature of catalysis, and functions to down-regulate HOCl synthesis and prevent hemoprotein heme destruction and/or protein modification.
PMID: 31103890
ISSN: 1873-3344
CID: 3978932

Reflections on preimplantation genetic testing for aneuploidy and mosaicism: how did we get here, and what does it mean clinically? [Comment]

Garvin, Sicily E; Chatzicharalampous, Charalampos; Puscheck, Elizabeth
PMID: 30611414
ISSN: 1556-5653
CID: 3978922

ARGINASE II AND NITRIC OXIDE SYNTHASE UNCOUPLING - A CULPRIT FOR OOCYTE QUALITY DETERIORATION IN OLDER PATIENTS?. [Meeting Abstract]

Chatzicharalampous, Charalampos; Awonuga, Awoniyi; Morris, Robert; Abu-Soud, Husam M.
ISI:000463487700067
ISSN: 0015-0282
CID: 3979022

The Role of Myeloperoxidase and Hypochlorous Acid in Oocyte Quality: A Friend or Foe? [Meeting Abstract]

Chatzicharalampous, Charalampos; Yahfoufi, Zeina; Morris, Robert T.; Awonuga, Awoniyi; Abu-Soud, Husam M.
ISI:000459610400660
ISSN: 1933-7191
CID: 3979032

Glyphosate and Fertility: The Missing Link. [Meeting Abstract]

Chatzicharalampous, Charalampos; Yahfoufi, Zeina A.; Khan, Sana N.; Morris, Robert T.; Awonuga, Awoniyi; Abu-Soud, Husam M.
ISI:000459610400655
ISSN: 1933-7191
CID: 3979082