Lucjusz Jakubowski - Academia.edu (original) (raw)
Papers by Lucjusz Jakubowski
Reproductive Biology and Endocrinology, 2020
Background Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defecti... more Background Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defective GnRH secretion, that is usually diagnosed in late adolescence or early adulthood due to the lack of spontaneous pubertal development. To date more than 30 genes have been associated with CHH pathogenesis with X-linked recessive, autosomal dominant, autosomal recessive and oligogenic modes of inheritance. Defective sense of smell is present in about 50–60% of CHH patients and called Kallmann syndrome (KS), in contrast to patients with normal sense of smell referred to as normosmic CHH. ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH and have been extensively studied in many reported cohorts. Due to rarity and heterogenicity of the condition the mutational spectrum, even in classical CHH genes, have yet to be fully characterized. Methods To address this issue we screened for ANOS1 and FGFR1 variants in a cohort of 47 unrelated CHH subjects using targeted panel ...
Archives of Medical Science
IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalam... more IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown.Material and methodsTargeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state.ResultsHere we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PRO...
Prenatal Cardiology
This is a case report about very rare findings in 2nd half of pregnancy (after normal 1 trimester... more This is a case report about very rare findings in 2nd half of pregnancy (after normal 1 trimester scan ) at 18th week of gestation fetal macrosomia was detected unrelated to maternal diabetes, and acceleration fetal growth later on with unusual cardiac abnormalities (fetal cardiomegaly, cardiomyopathy, partial abnormal venous connection ). Progressive features of congestive heart failure with polyhydramnios in a fetus with estimated 5500 g predicted a poor outcome and severe neonatal condition, which was presented and discussed with the parents to be. Casearean section was performed at 33rd weeks of gestation due to maternal dyscomfort, severe legs edema and her tachypnoe. Baby boy was delivered with birth weight of 5050g, Apgar 4 with mutiple tumors. Conservative care was introduced and neonated died on the 3rd day. Differential diagnosis was discussed with special attention to Costello syndrome however without proved by genetic make-up from neonatal blood.
American Journal of Medical Genetics Part A
American journal of men's health, 2018
The present study was designed to address the hypothesis that exposure to specific air pollutants... more The present study was designed to address the hypothesis that exposure to specific air pollutants may impact human sperm Y:X chromosome ratio. The study population consisted of 195 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 15-300 mln/ml (WHO, 2010). Participants represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Participants were interviewed and provided a semen sample. The Y:X ratio was assessed by fluorescent in situ hybridization (FISH). Air quality data were obtained from the AirBase database. In multivariate analysis the significant reduction was observed in the proportion of Y/X chromosome bearing sperm and exposure to particulate matter >10 μm in aerodynamic diameter PM ( p = .009) and particulate matter <10 μm in aerodynamic diameter PM ( p = .023). The observed effects of a lower Y:X sperm chromosome ratio among men expo...
International Journal of Environmental Health Research
Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and b... more Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15-300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.
Occupational and Environmental Medicine, 2016
Environmental Pollution, 2016
In recent years, a trend toward a declining proportion of male births has been noted in several, ... more In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.
American Journal of Medical Genetics Part a, Sep 15, 2008
Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. Howeve... more Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 AE 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 AE 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 AE 1.6% for female carriers and 1.4 AE 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.
Journal of Applied Genetics, Feb 1, 2005
Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collec... more Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collectively known as rapid aneuploidy testing, are compared in this review. We discuss methodological problems and limitations of these various methods. All these techniques are believed to be accurate and carry a low risk of misdiagnosis, but they differ in terms of labour-intensity and amenability to automation and high throughput testing. The question how to apply them safely and economically in a clinical setting has not been answered yet. The discussed techniques are so far not used as stand-alone tests, but some of them are routinely applied as a preliminary test that shortens the waiting time for classic cytogenetic karyotyping. In the future, mainly because of economical reasons, these methods may replace cytogenetics in the category of patients who make up the majority of those currently offered prenatal karyotyping: patients with moderately increased risk and no abnormalities detected by ultrasound.
Endokrynologia Polska, 2005
Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amen... more Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM-non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1,
Advances in Medical Sciences, 2016
This study aimed to investigate early-life folate serum concentrations in children with food, inh... more This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2-72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed (P=0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes (P=0.045). A negative correlation was demonstrated between the FoxP3 expression in CD4(+)CD25(high)FoxP3(+) peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant (r=-0.339, P&amp;lt;0.05). The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.
Urology, 2016
To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a ... more To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a human sperm. It was shown that the role of nutrition, especially dietary pattern, remains unexamined as a risk factor in sperm aneuploidy. In contrast to the traditional analytical approach used in nutritional epidemiology, dietary pattern analysis considers overall diet rather than individual nutrients or foods. The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes and who had semen concentration of ≥15 (10(6)/ml) (World Health Organization, 2010). Sperm aneuploidy was assessed using multicolor fluorescent in situ hybridization (DNA probes specific for chromosomes 13, 18, 21, X, Y). Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Men were classified into 3 groups according to scores of each dietary pattern: Western, Mixed, Prudent. In multivariate analysis, Prudent dietary pattern characterized by high intakes of fish, chicken, fruit, cruciferous vegetables, tomatoes, leafy green vegetables, legumes, and whole grains decreases disomy of chromosomes XX and 21 (P = .01 and P = .005) compared with Western dietary pattern characterized by high intakes of red and processed meat, butter, high fat dairy, refined grains, pizza, snacks, high-energy drinks, and sweets. Higher consumption of Prudent dietary pattern was associated with decreased frequencies of sperm disomy. As this is the first study to analyze the relation of diet and the frequency of sperm aneuploidy, our findings merit further studies, in other populations.
Hormone Metab Res, 1981
Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter... more Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter's syndrome was studied. Among the patients with Turner's syndrome hydroxyproline excretion was relatively low in girls 11-14 years old and somewhat increased in 14-17 age groups. Above 17 years of age urinary total hydroxyproline excretion was significantly higher than in the control. In patients with Klinefelter's syndrome at the age below 11 and above 17 years normal hydroxyproline values were observed. In 3 sixteen-year-old boys with 47, XXY karyotype, excretion of hydroxyproline with urine was significantly lower than in the control. Relatively low values of total hydroxyproline in urine of 11-14 year-old girls with Turner's syndrome and decreased in boys with Klinefelter's syndrome result, most probably, from the absence of hormonal changes typical for the puberty. However, concentration of hydroxyproline in urine does not correlate with serum FSH and LH levels. It is not affected by the enhancement of changes in the bone system either. The presented data encourage further studies on the connective tissue biochemistry in the patients with numerical aberrations sex chromosomes.
Endokrynologia Polska, 2015
According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diag... more According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diagnosis of exclusion. Here, we present a case of a 31-year-old woman with a history of oligomenorrhoea and hirsutism, who, despite a "muscular" appearance and a normal body mass index (22.27 kg/m 2), was found to have an extreme insulin resistance and diabetes accompanied by hyperandrogenism and polycystic ovaries. An autoimmune screen for possible latent autoimmune diabetes in adults was negative. She was subsequently found to have familial partial lipodystrophy (FPLD2, OMIM #151660) caused by an R482Q mutation in the LMNA gene encoding lamin A/C. This mutation results in arginine to glutamine substitution at the protein level, while phenotypically this condition presents with a loss of body fat, insulin resistance, dyslipidaemia, and other features mimicking PCOS. Interestingly her mother, with a history of myocardial infarction and diabetes at the age of 46 but no oligomenorrhoea, was also found to harbour the same mutation (LMNA R482Q). Conclusions: Our case highlights the importance of assessment of adipose tissue distribution, as well as a significance of assessment of glucose tolerance and insulin resistance in the differential diagnosis of PCOS. Furthermore, patients with atypical adipose tissue distribution should be referred for formal genetic testing.
Reproduction, fertility, and development, Jan 10, 2015
The purpose of this cross-sectional study was to investigate whether environmental exposure to po... more The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106 spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20×106 spermatozoa mL-1; <a href=
Endokrynologia Polska, 2011
Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where hypogonadotropic hypogonadism (H... more Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where hypogonadotropic hypogonadism (HH) associated with an impaired sense of smell is observed. The aim of this study was to investigate the usefulness of the multiplex ligation-dependent probe amplification (MLPA) technique for differential diagnosis in comparison with molecular cytogenetics - fluorescence in situ hybridisation (FISH) or traditional PCR analysis and propose a diagnostic approach for patients with KS. Karyotype and PCR analysis in two related patients and other family members were performed, followed by MLPA dosage sensitive analysis. In the proband and his maternal uncle, the PCR allowed the detection of a large deletion within the KAL1 gene, from exon 4 to 14 (c.469-?_6314+?del). The deletion was also diagnosed in three female carriers in the presented family. These results were proved by the MLPA technique. Moreover, we traced the presence of the region located downstream and upstream to the KAL1 gene on...
Kardiologia polska, 2005
Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to t... more Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to the debridement of the necrotic area as well as to initiation of repair followed by scar formation. The healing is a complex sequence of events consisted of four overlapping phases. Repair of the heart is under control of local and systemic regulatory factors. The knowledge of the mechanism of myocardial infarction allows to develop new strategies aimed at minimizing necrotic area and optimizing cardiac repair. This approach gives a chance to reduce the complications of myocardial infarction and to improve the quality of patients life.
Ginekologia polska, 2008
The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH... more The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH) diagnosed and treated in our institution from 1994-2006, and their follow-up. Retrospective analysis of the data base from Department for Diagnoses & Prevention of Fetal Malformations, Research Institute of the Polish Mother's Memorial Hospital: 14,481 fetal echo/ultrasound examinations in 10,077 fetuses have been analyzed to retrieve 115 fetuses with DH. The mean gestational age at the targeted US/ECHO examination was 30 wks. There were 8 terminations of pregnancies (at mean 21 wks), 6 intrauterine demises, 60 neonatal deaths after delivery (in 1-3rd day of postnatal life), 8 deaths after surgery, 19 neonates were discharged home and in 14 cases the follow-up could not be monitored. The most common anomalies accompanying DH have been central nervous system anomalies (20%), polyhydramnion (16%) and cong heart defects (10%). In this subgroup, there was 100% mortality. Isolated DH ha...
![Research paper thumbnail of [High risk of atherosclerosis in men aged 20-39 from Lodz agglomeration]](https://attachments.academia-assets.com/72707762/thumbnails/1.jpg)
](Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2007
To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of th... more To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of the highest in Poland fatality rate of circulatory system diseases. Anamnestic data on actual diseases, smoking, alcohol drinking and physical activity were achieved from 80 men, volunteers aged 20-39 years. Body weight and height, waist and hip circumference and arterial blood pressure were measured. Blood levels of lipids: total cholesterol (TCh), its fractions LDL, and HDL (LDL-Ch, HDL-Ch) ,and triglicerydes (TG), glucose, albumins, sex hormone binding globulin (SHBG), FSH, LH, total testosterone, dehydroepiandrosterone sulphate (DHEA-S) and estradiol were determined. Calculated were body mass index (BMI), waist to hip ratio (WHR), free testosterone index (FTI), free and bioactive testosterone. At least 3 atherosclerosis risk factors were simultaneously found in 33.7% of men, of which 22.7% were 20-29-year-old and 47.2% 30-39-year-old subjects. Elevated values of TG were found in 16.2% ...
Reproductive Biology and Endocrinology, 2020
Background Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defecti... more Background Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defective GnRH secretion, that is usually diagnosed in late adolescence or early adulthood due to the lack of spontaneous pubertal development. To date more than 30 genes have been associated with CHH pathogenesis with X-linked recessive, autosomal dominant, autosomal recessive and oligogenic modes of inheritance. Defective sense of smell is present in about 50–60% of CHH patients and called Kallmann syndrome (KS), in contrast to patients with normal sense of smell referred to as normosmic CHH. ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH and have been extensively studied in many reported cohorts. Due to rarity and heterogenicity of the condition the mutational spectrum, even in classical CHH genes, have yet to be fully characterized. Methods To address this issue we screened for ANOS1 and FGFR1 variants in a cohort of 47 unrelated CHH subjects using targeted panel ...
Archives of Medical Science
IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalam... more IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown.Material and methodsTargeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state.ResultsHere we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PRO...
Prenatal Cardiology
This is a case report about very rare findings in 2nd half of pregnancy (after normal 1 trimester... more This is a case report about very rare findings in 2nd half of pregnancy (after normal 1 trimester scan ) at 18th week of gestation fetal macrosomia was detected unrelated to maternal diabetes, and acceleration fetal growth later on with unusual cardiac abnormalities (fetal cardiomegaly, cardiomyopathy, partial abnormal venous connection ). Progressive features of congestive heart failure with polyhydramnios in a fetus with estimated 5500 g predicted a poor outcome and severe neonatal condition, which was presented and discussed with the parents to be. Casearean section was performed at 33rd weeks of gestation due to maternal dyscomfort, severe legs edema and her tachypnoe. Baby boy was delivered with birth weight of 5050g, Apgar 4 with mutiple tumors. Conservative care was introduced and neonated died on the 3rd day. Differential diagnosis was discussed with special attention to Costello syndrome however without proved by genetic make-up from neonatal blood.
American Journal of Medical Genetics Part A
American journal of men's health, 2018
The present study was designed to address the hypothesis that exposure to specific air pollutants... more The present study was designed to address the hypothesis that exposure to specific air pollutants may impact human sperm Y:X chromosome ratio. The study population consisted of 195 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 15-300 mln/ml (WHO, 2010). Participants represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Participants were interviewed and provided a semen sample. The Y:X ratio was assessed by fluorescent in situ hybridization (FISH). Air quality data were obtained from the AirBase database. In multivariate analysis the significant reduction was observed in the proportion of Y/X chromosome bearing sperm and exposure to particulate matter >10 μm in aerodynamic diameter PM ( p = .009) and particulate matter <10 μm in aerodynamic diameter PM ( p = .023). The observed effects of a lower Y:X sperm chromosome ratio among men expo...
International Journal of Environmental Health Research
Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and b... more Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15-300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.
Occupational and Environmental Medicine, 2016
Environmental Pollution, 2016
In recent years, a trend toward a declining proportion of male births has been noted in several, ... more In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.
American Journal of Medical Genetics Part a, Sep 15, 2008
Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. Howeve... more Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 AE 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 AE 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 AE 1.6% for female carriers and 1.4 AE 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.
Journal of Applied Genetics, Feb 1, 2005
Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collec... more Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collectively known as rapid aneuploidy testing, are compared in this review. We discuss methodological problems and limitations of these various methods. All these techniques are believed to be accurate and carry a low risk of misdiagnosis, but they differ in terms of labour-intensity and amenability to automation and high throughput testing. The question how to apply them safely and economically in a clinical setting has not been answered yet. The discussed techniques are so far not used as stand-alone tests, but some of them are routinely applied as a preliminary test that shortens the waiting time for classic cytogenetic karyotyping. In the future, mainly because of economical reasons, these methods may replace cytogenetics in the category of patients who make up the majority of those currently offered prenatal karyotyping: patients with moderately increased risk and no abnormalities detected by ultrasound.
Endokrynologia Polska, 2005
Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amen... more Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM-non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1,
Advances in Medical Sciences, 2016
This study aimed to investigate early-life folate serum concentrations in children with food, inh... more This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2-72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed (P=0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes (P=0.045). A negative correlation was demonstrated between the FoxP3 expression in CD4(+)CD25(high)FoxP3(+) peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant (r=-0.339, P&amp;lt;0.05). The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.
Urology, 2016
To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a ... more To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a human sperm. It was shown that the role of nutrition, especially dietary pattern, remains unexamined as a risk factor in sperm aneuploidy. In contrast to the traditional analytical approach used in nutritional epidemiology, dietary pattern analysis considers overall diet rather than individual nutrients or foods. The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes and who had semen concentration of ≥15 (10(6)/ml) (World Health Organization, 2010). Sperm aneuploidy was assessed using multicolor fluorescent in situ hybridization (DNA probes specific for chromosomes 13, 18, 21, X, Y). Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Men were classified into 3 groups according to scores of each dietary pattern: Western, Mixed, Prudent. In multivariate analysis, Prudent dietary pattern characterized by high intakes of fish, chicken, fruit, cruciferous vegetables, tomatoes, leafy green vegetables, legumes, and whole grains decreases disomy of chromosomes XX and 21 (P = .01 and P = .005) compared with Western dietary pattern characterized by high intakes of red and processed meat, butter, high fat dairy, refined grains, pizza, snacks, high-energy drinks, and sweets. Higher consumption of Prudent dietary pattern was associated with decreased frequencies of sperm disomy. As this is the first study to analyze the relation of diet and the frequency of sperm aneuploidy, our findings merit further studies, in other populations.
Hormone Metab Res, 1981
Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter... more Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter's syndrome was studied. Among the patients with Turner's syndrome hydroxyproline excretion was relatively low in girls 11-14 years old and somewhat increased in 14-17 age groups. Above 17 years of age urinary total hydroxyproline excretion was significantly higher than in the control. In patients with Klinefelter's syndrome at the age below 11 and above 17 years normal hydroxyproline values were observed. In 3 sixteen-year-old boys with 47, XXY karyotype, excretion of hydroxyproline with urine was significantly lower than in the control. Relatively low values of total hydroxyproline in urine of 11-14 year-old girls with Turner's syndrome and decreased in boys with Klinefelter's syndrome result, most probably, from the absence of hormonal changes typical for the puberty. However, concentration of hydroxyproline in urine does not correlate with serum FSH and LH levels. It is not affected by the enhancement of changes in the bone system either. The presented data encourage further studies on the connective tissue biochemistry in the patients with numerical aberrations sex chromosomes.
Endokrynologia Polska, 2015
According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diag... more According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diagnosis of exclusion. Here, we present a case of a 31-year-old woman with a history of oligomenorrhoea and hirsutism, who, despite a "muscular" appearance and a normal body mass index (22.27 kg/m 2), was found to have an extreme insulin resistance and diabetes accompanied by hyperandrogenism and polycystic ovaries. An autoimmune screen for possible latent autoimmune diabetes in adults was negative. She was subsequently found to have familial partial lipodystrophy (FPLD2, OMIM #151660) caused by an R482Q mutation in the LMNA gene encoding lamin A/C. This mutation results in arginine to glutamine substitution at the protein level, while phenotypically this condition presents with a loss of body fat, insulin resistance, dyslipidaemia, and other features mimicking PCOS. Interestingly her mother, with a history of myocardial infarction and diabetes at the age of 46 but no oligomenorrhoea, was also found to harbour the same mutation (LMNA R482Q). Conclusions: Our case highlights the importance of assessment of adipose tissue distribution, as well as a significance of assessment of glucose tolerance and insulin resistance in the differential diagnosis of PCOS. Furthermore, patients with atypical adipose tissue distribution should be referred for formal genetic testing.
Reproduction, fertility, and development, Jan 10, 2015
The purpose of this cross-sectional study was to investigate whether environmental exposure to po... more The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106 spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20×106 spermatozoa mL-1; <a href=
Endokrynologia Polska, 2011
Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where hypogonadotropic hypogonadism (H... more Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where hypogonadotropic hypogonadism (HH) associated with an impaired sense of smell is observed. The aim of this study was to investigate the usefulness of the multiplex ligation-dependent probe amplification (MLPA) technique for differential diagnosis in comparison with molecular cytogenetics - fluorescence in situ hybridisation (FISH) or traditional PCR analysis and propose a diagnostic approach for patients with KS. Karyotype and PCR analysis in two related patients and other family members were performed, followed by MLPA dosage sensitive analysis. In the proband and his maternal uncle, the PCR allowed the detection of a large deletion within the KAL1 gene, from exon 4 to 14 (c.469-?_6314+?del). The deletion was also diagnosed in three female carriers in the presented family. These results were proved by the MLPA technique. Moreover, we traced the presence of the region located downstream and upstream to the KAL1 gene on...
Kardiologia polska, 2005
Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to t... more Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to the debridement of the necrotic area as well as to initiation of repair followed by scar formation. The healing is a complex sequence of events consisted of four overlapping phases. Repair of the heart is under control of local and systemic regulatory factors. The knowledge of the mechanism of myocardial infarction allows to develop new strategies aimed at minimizing necrotic area and optimizing cardiac repair. This approach gives a chance to reduce the complications of myocardial infarction and to improve the quality of patients life.
Ginekologia polska, 2008
The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH... more The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH) diagnosed and treated in our institution from 1994-2006, and their follow-up. Retrospective analysis of the data base from Department for Diagnoses & Prevention of Fetal Malformations, Research Institute of the Polish Mother's Memorial Hospital: 14,481 fetal echo/ultrasound examinations in 10,077 fetuses have been analyzed to retrieve 115 fetuses with DH. The mean gestational age at the targeted US/ECHO examination was 30 wks. There were 8 terminations of pregnancies (at mean 21 wks), 6 intrauterine demises, 60 neonatal deaths after delivery (in 1-3rd day of postnatal life), 8 deaths after surgery, 19 neonates were discharged home and in 14 cases the follow-up could not be monitored. The most common anomalies accompanying DH have been central nervous system anomalies (20%), polyhydramnion (16%) and cong heart defects (10%). In this subgroup, there was 100% mortality. Isolated DH ha...
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2007
To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of th... more To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of the highest in Poland fatality rate of circulatory system diseases. Anamnestic data on actual diseases, smoking, alcohol drinking and physical activity were achieved from 80 men, volunteers aged 20-39 years. Body weight and height, waist and hip circumference and arterial blood pressure were measured. Blood levels of lipids: total cholesterol (TCh), its fractions LDL, and HDL (LDL-Ch, HDL-Ch) ,and triglicerydes (TG), glucose, albumins, sex hormone binding globulin (SHBG), FSH, LH, total testosterone, dehydroepiandrosterone sulphate (DHEA-S) and estradiol were determined. Calculated were body mass index (BMI), waist to hip ratio (WHR), free testosterone index (FTI), free and bioactive testosterone. At least 3 atherosclerosis risk factors were simultaneously found in 33.7% of men, of which 22.7% were 20-29-year-old and 47.2% 30-39-year-old subjects. Elevated values of TG were found in 16.2% ...