Publications by authors named "Antonios Makrigiannakis"

11 Publications

  • Page 1 of 1

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review.

Int J Environ Res Public Health 2021 Feb 4;18(4). Epub 2021 Feb 4.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.
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http://dx.doi.org/10.3390/ijerph18041464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913912PMC
February 2021

Intrauterine G-CSF Administration in Recurrent Implantation Failure (RIF): An Rct.

Sci Rep 2020 03 20;10(1):5139. Epub 2020 Mar 20.

Bahcesehir University, Department of Obstetrics and Gynecology, Istanbul, Turkey.

This study investigates the effects of intrauterine G-CSF on endometrial thickness, clinical pregnancy rate and live birth rate in a recurrent implantation failure (RIF) group with normal endometrium. This study was designed as a prospective randomized controlled trial with the involvement of 157 RIF group pati; ents. The RIF group was formed on the basis of the RIF criteria: "The failure to achieve a clinical pregnancy after the transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles to a woman under the age of 40 years. The study sample included 82 patients in the G-CSF group who received G-CSF once a day on hCG. The procedure was performed by administering 30 mIU of Leucostim®(Filgrastim [G-CSF] 30 mIU/mL; DEM Medical, Dong-A; South Korea) through slow infusion into the endometrial cavity using a soft embryo transfer catheter. Normal saline of 1 mL was infused into the endometrial cavity in the same way in 75 patients in the control group. The standard ICSI procedure was used for all patients, and fresh cycle embryos were transferred on the third or fifth day. No statistically significant difference was identified in clinical pregnancy rates, miscarriage rates and live birth rates between the G-CSF group and the control group (p = 0.112, p = 0.171, p = 0.644, respectively), and no difference was observed between the two groups regarding endometrial thickness (p = 0.965). The intervention of administration G-CSF into the uterine cavity in RIF patients with normal endometrium, did not alter the endometrial thickness, clinical pregnancy rates, or live birth rates.
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http://dx.doi.org/10.1038/s41598-020-61955-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083859PMC
March 2020

A prospective, cross-sectional study of the protective and risk psychological factors of successful fertilisation outcome: preliminary results in a Greek sample.

J Obstet Gynaecol 2020 Apr 1;40(3):382-387. Epub 2019 Sep 1.

Department of Obstetrics and Gynecology, School of Medicine, University Hospital of Heraklion, University of Crete, Heraklion, Greece.

The aim of this prospective, cross-sectional study was to examine the protective and risk psychological factors associated with the successful outcome of In fertilisation (IVF). Various psychological factors that may affect the IVF outcome were measured to a sample of 61 infertile women (mean age 37.2 ± 4.4), who started their first or consecutive IVF treatment cycle in an IVF Unit in Greece. Over half of the participants (50.8%) became pregnant. A binary logistic regression analysis (stepwise) was conducted on pregnancy as the outcome, with various variables as predictors. The model was statistically significant (Omnibus Chi-square = 27.324,  = 5,  < .001), explained 54.7% of the variance, and correctly classified 84.6% of the cases. Life purpose (odds ratio [OR] = 1.35, 95% CI = 1.02-1.78) and negative emotions (e.g. discontent, sorrow) (OR = 1.76, 95% CI = 1.19-2.60) were associated with increased pregnancy rates, whereas autonomy (OR = 0.57, 95% CI = 0.39-0.82), and stress (OR = 0.69, 95% CI = 0.55-0.88) were associated with decreased pregnancy rates. It has been concluded that the relationship between psychological factors and successful IVF outcome is more complex than commonly believed. The identification of the risk and protective psychological factors could contribute to increased pregnancy rates and foster the implementation of tailored therapeutic interventions.Impact statement High levels of infertility stress and/or depression have been associated with lower pregnancy rates. However, little is known on the impact of emotions, personality characteristics and other psychological variables on in vitro fertilisation (IVF) outcome. A combination of commonly believed 'negative' factors (e.g. stress) and 'positive' ones (e.g. well-being) may diversely affect the IVF outcome. Otherwise believed to be positive aspects of human life (i.e. autonomy) may decrease the likelihood of pregnancy, and other factors believed to be 'negative' (e.g. negative emotions) may increase pregnancy rates. The findings invite researchers to further examine the role of the psychological factors which could potentially affect pregnancy rates. Modifiable factors, such as well-being, stress and emotions, should guide tailored interventions aimed at increasing the pregnancy rates in infertile women.
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http://dx.doi.org/10.1080/01443615.2019.1631766DOI Listing
April 2020

The association of female and male infertility with telomere length (Review).

Int J Mol Med 2019 Aug 31;44(2):375-389. Epub 2019 May 31.

Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece.

Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of genome integrity and are vital to cellular functions. Traditionally, a strong link connects aging and infertility in both sexes, with an earlier onset in females. Over the past decade, telomeres have attracted increasing attention due to the role they play in fertility. In this review, we investigated the potential positive or negative association between relative TL and different factors of female and male infertility. A systematic search of the PubMed database was conducted. Out of the 206 studies identified, 45 were reviewed as they fulfilled the criteria of validity and relevance. Following an analysis and a comparison of the study outcomes, several clear trends were observed. The majority of female infertility factors were associated with a shorter TL, with the exception of endometriosis, premature ovarian failure and clear cell carcinoma that were associated with a longer TL and polycystic ovary syndrome (PCOS), which revealed conflicting results among several studies, leading to ambiguous conclusions. Male infertility factors were associated with a shorter TL. Although this review can provide an outline of general trends in the association of TL with infertility factors, further epidemiological and original research studies are required to focus on investigating the basis of these varying lengths of telomeres.
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http://dx.doi.org/10.3892/ijmm.2019.4225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605974PMC
August 2019

Endocrine Disruptors Leading to Obesity and Related Diseases.

Int J Environ Res Public Health 2017 10 24;14(10). Epub 2017 Oct 24.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Crete, Greece.

The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs) in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs. Specific population groups are vulnerable to ED exposure due to current dietary and environmental conditions. Obesity, morbidity and carcinogenicity induced by ED exposure are an evolving reality. Therefore, a new collective strategic approach is deemed essential, for the reappraisal of current global conditions pertaining to energy management.
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http://dx.doi.org/10.3390/ijerph14101282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664782PMC
October 2017

Association of placental inflammation with fetomaternal hemorrhage and loss of placental mucin-1.

Arch Gynecol Obstet 2012 Mar 30;285(3):605-12. Epub 2011 Jul 30.

Department of Obstetrics and Gynecology, Medical Faculty, Heinrich-Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany.

Background: Fetomaternal hemorrhage (FMH) poses an immediate risk to the fetus and, in case of Rhesus-immunization, to future pregnancies. Given that altered endothelial permeability is part of the pathophysiology of inflammation, in this study we investigated whether placental inflammatory processes like chorioamnionitis (ChoA) or preeclampsia (PE) lead to increased rates of FMH compared to the established risk factor of placenta previa (PP). Putative accompanying markers of trophoblastic damage were also explored.

Methods: 40 patients (14 PE; 6 ChoA; 9 PP; 11 normal controls) were evaluated for FMH using a flowcytometric test kit, which is able to quantify FMH of 0.06% fetal cells. Placental tissue samples were immunostained for human placental lactogen (hPL), human chorionic gonadotropin (hCG), and mucin-1 (MUC1). MUC1 was evaluated as a potential serum marker of FMH.

Results: Patients with ChoA had a mean calculated FMH volume of 29 ml, compared to 4 ml in PE and 1 ml in PP and controls. MUC1 staining was reduced in PE and ChoA placenta samples, while elevated MUC1 serum concentration correlated positively with FMH.

Conclusion: Diseases of placental inflammation are associated with FMH. Placental MUC1 staining is reduced and serum concentrations are increased in cases of FMH.
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http://dx.doi.org/10.1007/s00404-011-2028-1DOI Listing
March 2012

Pregnancy after breast cancer. A comprehensive review.

J Surg Oncol 2010 May;101(6):534-42

Department of Surgical Oncology, Medical School of Crete University Hospital, Herakleion, Greece.

Pregnancy after breast cancer treatment has become an important issue since many young breast cancer patients have not completed their family. Generally, these patients should not be discouraged to become pregnant when they want to, since published data suggest no adverse effect of pregnancy on survival. As fertility may be impaired by chemotherapy, different fertility preserving strategies have been developed. Births seem to sustain no adverse effects, while breastfeeding appears to be feasible and safe.
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http://dx.doi.org/10.1002/jso.21514DOI Listing
May 2010

Prevalence of human herpes virus types 1-7 in the semen of men attending an infertility clinic and correlation with semen parameters.

Fertil Steril 2009 Jun 18;91(6):2487-94. Epub 2008 Jun 18.

Laboratory of Human Reproduction, IVF Clinic, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Crete, Crete, Greece.

Objective: To determine the prevalence of herpes viruses in the semen of an asymptomatic male cohort with and without infertility problems and its association with altered semen parameters.

Design: A prospective randomized study.

Setting: Medical school and IVF clinic.

Patient(s): One hundred seventy-two male patients undergoing routine semen analysis: 80 with normal semen parameters (control group) and 92 with abnormal semen parameters.

Intervention(s): Semen samples were collected by masturbation.

Main Outcome Measure(s): The DNA from the Herpesviridae family (herpes simplex virus 1 [HSV-1], herpes simplex virus 2 [HSV-2], Varicella zoster virus [VZV], Epstein-Barr virus [EBV], cytomegalovirus [CMV], human herpes virus type 6 [HHV-6], human herpes virus type 7 [HHV-7]) and routine semen parameters.

Result(s): Viral DNA was detected in 143/172 (83.1%) of the total samples for at least one herpes virus: HSV-1, 2.5%; VZV, 1.2%; EBV, 45%; CMV, 62.5%; HHV-6, 70%; HHV-7, 0% in the normal semen samples and HSV-1, 2.1%; VZV, 3.2%; EBV, 39.1%; CMV, 56.5%; HHV-6, 66.3%; HHV-7, 0% in the abnormal semen samples. No association was found between the presence of viral DNA and semen parameters. Interestingly, a statistical significance between leukocytospermia and the presence of EBV DNA was observed.

Conclusion(s): The DNA of herpes viruses is frequently detected in the semen of asymptomatic fertile and infertile male patients. Further studies are required to investigate the role of herpes viruses in male factor infertility.
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http://dx.doi.org/10.1016/j.fertnstert.2008.03.074DOI Listing
June 2009

Expression of the inhibin/activin subunits (-alpha, -betaA and -betaB) in normal and carcinogenic endometrial tissue: possible immunohistochemical differentiation markers.

Oncol Rep 2007 Jan;17(1):97-104

1st Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Munich, Maistrasse 11, 80337 Munich, Germany.

Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB), with substantial roles in human reproduction and in endocrine-responsive tumors. The aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in normal and malignant endometria. Samples were obtained from normal (n=46), atrophic (n=8) and endometrioid carcinoma tissue (EC; G1=93; G2=32; G3=14). INH-alpha was significantly higher in normal compared to malignant endometrial tissue, showing a cyclical variation throughout the menstrual cycle. EC G3 did not express this subunit. INH-betaA and -betaB showed specific staining reactions within the tumor cells. The highest intensity of INH-betaA was observed in the normal secretory phase compared to adenocarcinomas (p<0.05). For INH-betaB, the significantly highest expression was noted in EC G3 compared to EC G2 (p<0.05) and atrophic endometrial tissue. In conclusion, INH-alpha, -betaA and -betaB were immunolabeled in normal and malignant endometria. INH-alpha was expressed in a declining relationship in the transition from normal to tumor tissue, suggesting a tumor suppressive function in EC. A high expression of INH-betaB was observed in EC G3 compared to G2, suggesting an important role in the progression of endometrial carcinogenesis. However, the utilization of these subunits as specific tumor markers still remains unclear.
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January 2007

Laparoscopic evaluation of infertile patients with chronic pelvic pain.

Reprod Biomed Online 2006 Mar;12(3):347-53

1st Department of Obstetrics and Gynecology, University of Athens, Alexandra Hospital, Athens, Greece.

In this study over a 10-year period, 1584 patients complaining of infertility of more than 1 year duration were evaluated for their laparoscopic findings in relation to the presence or not of chronic pelvic pain (CPP). Infertility was the only complaint in 1215 cases (group 1), whereas 369 patients complained of infertility and CPP (group 2). All cases underwent routine infertility investigation and pelvic ultrasonography, followed by diagnostic laparoscopy, with infertility-only cases acting as a control group. At laparoscopy 76.7% of patients with CPP were found with pelvic pathology, compared with only 42.6% of cases without CPP (P < or = 0.0001). Omental-abdominal wall adhesions, advanced endometriosis, endometriomas with adhesions, pelvic venous congestion, and hydrosalpinges with pelvic adhesions were significantly more frequent in cases with CPP. Dysmenorrhoea was the most frequent type of CPP. Cases with CPP and a negative laparoscopy were further investigated using a multidisciplinary approach. In conclusion, chronic pelvic pain can be the result of several pelvic pathologies. Infertile patients with CPP are much more frequently found with an abnormal pelvis in comparison with cases without CPP. Laparoscopy is an invaluable diagnostic tool especially for symptomatic patients and should be used early in their diagnostic infertility work-up.
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http://dx.doi.org/10.1016/s1472-6483(10)61008-5DOI Listing
March 2006

3C syndrome with cryptorchidism and posterior embryotoxon.

Clin Dysmorphol 2005 Apr;14(2):97-100

Department of Pediatrics, University of Crete, Heraklion, Crete, Greece.

We report a case of the 3C (cranio-cerebello-cardiac) syndrome, also known as Ritscher-Schinzel syndrome, a rare autosomal recessive disorder characterized by craniofacial, cerebellar, and cardiac anomalies. In addition to features previously reported the child had Wormian bones of the skull, intra-abdominal testes, and posterior embryotoxon that have not previously been reported as part of the 3C syndrome.
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http://dx.doi.org/10.1097/00019605-200504000-00009DOI Listing
April 2005