Gian Tiboni - Academia.edu (original) (raw)

Papers by Gian Tiboni

Research paper thumbnail of Inhibition of nitric oxide synthesis enhances teratogenic effects induced by valproic Acid

PubMed, Jul 3, 2013

Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This... more Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity. Materials and methods: On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation. Results: After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%. Conclusion: Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis.

Research paper thumbnail of Inhibition of nitric oxide synthesis enhances the teratogenic response to valproic acid

Reproductive Toxicology, Nov 1, 2013

ABSTRACT Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly kn... more ABSTRACT Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity. On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation. After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%. Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis.

Research paper thumbnail of Non-O blood group and outcomes of in vitro fertilization

Journal of Assisted Reproduction and Genetics, Apr 20, 2018

Purpose Retrospective and cross-sectional studies suggested that non-O blood group may be associa... more Purpose Retrospective and cross-sectional studies suggested that non-O blood group may be associated with failures of in vitro fertilization (IVF), but data remain controversial. The aim of this observational cohort study was to prospectively evaluate the effect of non-O blood type on clinical outcomes of IVF. Methods Women < 40 years who underwent IVF and had ABO blood type recorded as part of the routine workup were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, positive pregnancy test, and clinical pregnancy. Results A total of 497 women with a mean age of 34.6 (standard deviation 3.2) years were included. The mean number of embryos transferred was 2.3 (standard deviation 0.6). The most common ABO blood types were O (n = 213, 42.9%) and A (n = 203, 40.8%), while 63 (12.7%) and 18 (3.6%) women had the B and AB blood types, respectively. Differences in live birth (21.8 vs. 24.3%, odds ratio [OR] 1.17; 95% confidence intervals [CI], 0.76 to 1.78), positive pregnancy test (37.9 vs. 36.6%, OR 0.96; 95% CI, 0.66 to 1.38), clinical pregnancy (35.1 vs. 33.8%, OR 0.95; 95% CI, 0.66 to 1.39), and spontaneous abortion (12.3 vs. 9.2%, OR 0.72; 95% CI, 0.41 to 1.29) between women with O and non-O blood type were not statistically significant. Conclusions In a prospective cohort study, we confirmed the lack of a significant association between non-O blood type and clinical outcomes of IVF. Further studies are needed to clarify whether non-O blood group has any prognostic relevance in women undergoing IVF.

Research paper thumbnail of Cigarette smoking impairs clinical outcomes of assisted reproductive technologies: A meta-analysis of the literature

Reproductive Toxicology, Sep 1, 2018

 This meta-analysis updated the knowledge regarding the effects of cigarette smoke on the clinic... more  This meta-analysis updated the knowledge regarding the effects of cigarette smoke on the clinical outcomes of assisted reproductive technologies (ART).  Cigarette smoking is associated with a significant decrease in live birth rate and clinical pregnancy rate and with an increase in terms of spontaneous miscarriage rate for smokers.

Research paper thumbnail of Meet Our Editorial Board Member

Current Pharmaceutical Biotechnology, Jan 13, 2017

He organized several international and national meetings and symposia (IBRO meeting, Glia confere... more He organized several international and national meetings and symposia (IBRO meeting, Glia conferences etc.). His projects were funded by the EU, DFG, DAAD,national foundations and several industrial companies. He received several awards among them the MerckleForschungspreis 2001, the price of the Society of Steroid Biochemistry in 2002, and the RWTH Teaching Award in 2007. He is a member of the Editorial board of several peer-review journals such as the Annals of Anatomy and Current Neuropharmacology, and published several special issues in the Journal of Biochemistry and Molecular Biology. To this day, he published more than 190 peer reviewed articles with more than 3500 citations.

Research paper thumbnail of Folate serum levels in Italian women entering an in vitro fertilization program

Gynecological Endocrinology, Jul 19, 2017

Italian public health authorities recommend women of childbearing age to assume a daily dose of 0... more Italian public health authorities recommend women of childbearing age to assume a daily dose of 0.4 mg of folic acid (FA) from at least one month before conception in order to reduce the risk of having children affected by neural tube defects (NTDs). In this study, folate, homocysteine and vitamin B12 serum levels were determined in 77 women entering an in vitro fertilization program. About 75% of patients had serum folate values compatible with the intake of the recommended dose of FA for at least three months, whereas only the 61% of them reached or exceeded the serum folate concentration regarded as the optimal concentration during the periconceptional period. Mean vitamin B12 serum levels and mean homocysteine plasma levels resulted in normal range in all the women with mean values of 381.2 ± 2.2 pg/ml and 8.48 ± 2.2 lmol/l, respectively. In conclusion, only a portion of women entering an IVF program presents proper folate levels.

Research paper thumbnail of Teratology of valproic acid: an updated review of the possible mediating mechanisms

Minerva obstetrics and gynecology, May 1, 2018

Valproic acid (VPA) is an anti-epileptic drug (AED) which is currently being investigated for its... more Valproic acid (VPA) is an anti-epileptic drug (AED) which is currently being investigated for its potential application in the treatment of several types of cancers, including solid and non-solid tumor. It is well-known that prenatal exposure to VPA largely increases the risk for malformations and other developmental disorders. This review concentrates on clinical and experimental data on congenital anomalies attributed to maternal VPA exposure. Particular emphasis is placed on the potential mechanisms underlying VPA-induced malformations. Although several mechanisms have been suggested, there appears to be no data in the literature in support of a single definitive mechanism for VPA-exposure-related fetal malformations.

Research paper thumbnail of Editorial: Teratology and Reproductive Toxicology of Anticancer Agents

Anti-cancer Agents in Medicinal Chemistry, Sep 12, 2017

Research paper thumbnail of Fetal safety profile of aromatase inhibitors: Animal data

Reproductive Toxicology, Dec 1, 2016

Aromatase inhibitors (AIs) are a class of drugs that act by blocking the production of estrogens ... more Aromatase inhibitors (AIs) are a class of drugs that act by blocking the production of estrogens from androgens. The current review concentrates on the prenatal developmental toxicity of AIs in experimental models. Available data indicate that AIs may affect pregnancy at human therapeutic or lower doses. The window of vulnerability to AIs is not limited to organogenesis, but also includes the preimplantation stage and fetal periods. Decreased embryo/fetal survival was the prominent treatment-related effect. Morphological anomalies noted in fetuses exposed to AIs included skeletal anomalies, abnormal head morphology, increased ano-genital distance in female fetuses, and minor urinary tract system anomalies. Placental enlargement was consistently reported in rats and non-human primates after maternal treatment with several AIs. In conclusion, data from basic scientific research suggest that low intensity exposure to AIs applied during a wide gestational window can profoundly affect prenatal development.

Research paper thumbnail of Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization

Thrombosis Research, Jul 1, 2018

Research paper thumbnail of Ovotoxicity of cigarette smoke: A systematic review of the literature

Reproductive Toxicology, Sep 1, 2017

Highlights  Cigarette smoke negatively affects ovarian folliculogenesis.  The hypothesized caus... more Highlights  Cigarette smoke negatively affects ovarian folliculogenesis.  The hypothesized causes of ovarian damage include increased oxidative stress, increased cellular apoptosis or autophagy, DNA damage and abnormal crosstalk between oocyte and granulosa cells.

Research paper thumbnail of Nutrition, female fertility and in vitro fertilization outcomes

Reproductive Toxicology, Jun 1, 2023

Research paper thumbnail of In utero exposure to valproic acid during neurulation alters nitric oxide synthase isoforms expression

Reproductive Toxicology, Sep 1, 2016

Research paper thumbnail of Inhibition of nitric oxide synthesis causes pre-term delivery in the mouse

International journal of gynaecology and obstetrics, 2000

NO has been recently postulated as having a role in the complex molecular interplay which regulat... more NO has been recently postulated as having a role in the complex molecular interplay which regulates myometrial func-Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e tion during gestation (Norman, 1996; Sladek et al, 1997;

Research paper thumbnail of Thyroid autoimmunity and assisted reproductive technology (ART)

10th European Congress of Endocrinology, May 1, 2008

About 105 women (mean age 35.7+4.7) have been investigated; 11 subjects have been excluded from t... more About 105 women (mean age 35.7+4.7) have been investigated; 11 subjects have been excluded from the study because of known thyroid diseases. The remaining 95 women have been divided according to the cause of infertility; 34% were idiopathic, 26.6% had a male factor, 6.4% ...

Research paper thumbnail of Effect of vitamin D supplementation on uterine fibroids: a meta-analysis of the literature

Minerva obstetrics and gynecology, Apr 1, 2022

Research paper thumbnail of In Vivo Cigarette Smoke Exposure to Examine the Expression of Genes Involved in the Inflammatory Response in the Mouse Uterus

Current protocols, Jun 1, 2021

Cigarette smoke may impair uterine function, but the underlying mechanisms are poorly characteriz... more Cigarette smoke may impair uterine function, but the underlying mechanisms are poorly characterized. In this article, we describe the methodology for whole‐body exposure to cigarette smoke together with assessment of the impact of this exposure on the expression of a panel of genes related to stress and toxicity pathways in mouse uteri using an in vivo model. C57BL/6 mice are whole‐body‐exposed to three cigarettes daily, 7 days/week, for 2 months using a specific rodent ventilator. Uteri are then collected and subjected to qRT‐PCR analysis using the Stress & Toxicity PathwayFinder RT2 Profiler PCR Array (Qiagen). Cigarette smoke was found to be associated with an upregulation (≥2‐fold) of C‐reactive protein (Crp; 2.65‐fold, p‐value = 0.02), growth arrest and DNA‐damage‐inducible45γ (Gadd45γ; 2.11‐fold, p‐value = 0.04), interferon γ (Ifnγ; 2.05‐fold, p‐value = 0.01), and interleukin1α (Il1α; 7.74‐fold, p‐value = 0.003) and downregulation of matrix metallopeptidase‐9 (Mmp9; −2.42‐fold, p‐value = 0.01). The protocol used in this study may represent a new experimental model of mouse in vivo mainstream exposure to cigarette smoke. In addition, the resulting overexpression of pro‐inflammatory cytokines and genes involved in cell cycle proliferation, together with the downregulation of extracellular matrix metallopeptidases, may represent a toxicological response to cigarette smoke exposure, with potential repercussion for the processes of uterine remodeling and growth that are essential for uterine receptiveness. A recommendation to expand upon this research area is made. © 2021 Wiley Periodicals LLC.

Research paper thumbnail of MRAP2 regulates endometrial receptivity and function

Gene, Jun 1, 2019

A successful embryo implantation depends on the synchronization between a competent blastocyst an... more A successful embryo implantation depends on the synchronization between a competent blastocyst and a receptive endometrium. Recently, potential modulators of endometrial receptivity (OVGP1, MRAP2, ZCCHC12, and HAP1) have been reported likely with a functional role during embryo implantation. The aim of this study was to evaluate the gene expression of these genes in the endometrium of infertile women. Eighteen endometrial biopsies, during secretory lutheal phase, were recruited from women with unexplained infertility and women who cannot conceive due to their partners' fertility problems. qRT-PCR was carried out to evaluate MRAP2, OVGP1, ZCCHC12 and HAP1 gene expression. MRAP2 expression was also detected by western blot and it was localized by immunohistochemistry. Morphological analysis was performed by light microscopy. MRAP2 was significantly up-regulated in study vs. control group. Western blot analysis confirmed the observed MRAP2 up-expression. MRAP2 resulted mainly localized in the epithelial cells of uterine glands. Morphological analysis displayed that the epithelium of the uterine glands undergo hypertrophy in women with unexplained infertility in respect to women with male infertility factor. MRAP2 could be considered a mediator of endometrial receptivity likely acting on endometrial stability by binding to MCRs and PKR1.

Research paper thumbnail of An updated meta-analysis comparing the efficacy and safety of biosimilar medicinal products to the original follitropin alfa

Minerva Obstetrics and Gynecology

Research paper thumbnail of Profiling of mitochondrial heteroplasmy in single human oocytes by next‐generation sequencing

Molecular Reproduction and Development

Mitochondrial DNA (mtDNA) plays a crucial role in the development of a competent oocyte. Indeed, ... more Mitochondrial DNA (mtDNA) plays a crucial role in the development of a competent oocyte. Indeed, mtDNA alterations may predispose to chromosome nondisjunction, resulting in infertility due to a reduced vitality and quality of oocytes and embryos. In this methods paper, the multiple displacement amplification approach was applied in combination with next‐generation sequencing (NGS) to amplify and sequence, in single‐end, the entire mtDNA of single human oocytes to directly construct genomic NGS libraries, and subsequently, to highlight and quantify the mutations they presented. The bioinformatic workflow was carried out with a specific ad hoc developed in‐house software. This approach proved to be sensitive and specific, also highlighting the mutations present in heteroplasmy, showing deletion, insertion or substitution mutations in the genes involved in the respiratory chain, even if the found variants were benign or of uncertain meaning. The analysis of mtDNA mutations in the oocyte could provide a better understanding of specific genetic abnormalities and of their possible effect on oocyte developmental competence. This study shows how this approach, based on a massive parallel sequencing of clonally amplified DNA molecules, allows to sequence the entire mitochondrial genome of single oocytes in a short time and with a single analytical run and to verify mtDNA mutations.

Research paper thumbnail of Inhibition of nitric oxide synthesis enhances teratogenic effects induced by valproic Acid

PubMed, Jul 3, 2013

Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This... more Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity. Materials and methods: On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation. Results: After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%. Conclusion: Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis.

Research paper thumbnail of Inhibition of nitric oxide synthesis enhances the teratogenic response to valproic acid

Reproductive Toxicology, Nov 1, 2013

ABSTRACT Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly kn... more ABSTRACT Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity. On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation. After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%. Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis.

Research paper thumbnail of Non-O blood group and outcomes of in vitro fertilization

Journal of Assisted Reproduction and Genetics, Apr 20, 2018

Purpose Retrospective and cross-sectional studies suggested that non-O blood group may be associa... more Purpose Retrospective and cross-sectional studies suggested that non-O blood group may be associated with failures of in vitro fertilization (IVF), but data remain controversial. The aim of this observational cohort study was to prospectively evaluate the effect of non-O blood type on clinical outcomes of IVF. Methods Women < 40 years who underwent IVF and had ABO blood type recorded as part of the routine workup were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, positive pregnancy test, and clinical pregnancy. Results A total of 497 women with a mean age of 34.6 (standard deviation 3.2) years were included. The mean number of embryos transferred was 2.3 (standard deviation 0.6). The most common ABO blood types were O (n = 213, 42.9%) and A (n = 203, 40.8%), while 63 (12.7%) and 18 (3.6%) women had the B and AB blood types, respectively. Differences in live birth (21.8 vs. 24.3%, odds ratio [OR] 1.17; 95% confidence intervals [CI], 0.76 to 1.78), positive pregnancy test (37.9 vs. 36.6%, OR 0.96; 95% CI, 0.66 to 1.38), clinical pregnancy (35.1 vs. 33.8%, OR 0.95; 95% CI, 0.66 to 1.39), and spontaneous abortion (12.3 vs. 9.2%, OR 0.72; 95% CI, 0.41 to 1.29) between women with O and non-O blood type were not statistically significant. Conclusions In a prospective cohort study, we confirmed the lack of a significant association between non-O blood type and clinical outcomes of IVF. Further studies are needed to clarify whether non-O blood group has any prognostic relevance in women undergoing IVF.

Research paper thumbnail of Cigarette smoking impairs clinical outcomes of assisted reproductive technologies: A meta-analysis of the literature

Reproductive Toxicology, Sep 1, 2018

 This meta-analysis updated the knowledge regarding the effects of cigarette smoke on the clinic... more  This meta-analysis updated the knowledge regarding the effects of cigarette smoke on the clinical outcomes of assisted reproductive technologies (ART).  Cigarette smoking is associated with a significant decrease in live birth rate and clinical pregnancy rate and with an increase in terms of spontaneous miscarriage rate for smokers.

Research paper thumbnail of Meet Our Editorial Board Member

Current Pharmaceutical Biotechnology, Jan 13, 2017

He organized several international and national meetings and symposia (IBRO meeting, Glia confere... more He organized several international and national meetings and symposia (IBRO meeting, Glia conferences etc.). His projects were funded by the EU, DFG, DAAD,national foundations and several industrial companies. He received several awards among them the MerckleForschungspreis 2001, the price of the Society of Steroid Biochemistry in 2002, and the RWTH Teaching Award in 2007. He is a member of the Editorial board of several peer-review journals such as the Annals of Anatomy and Current Neuropharmacology, and published several special issues in the Journal of Biochemistry and Molecular Biology. To this day, he published more than 190 peer reviewed articles with more than 3500 citations.

Research paper thumbnail of Folate serum levels in Italian women entering an in vitro fertilization program

Gynecological Endocrinology, Jul 19, 2017

Italian public health authorities recommend women of childbearing age to assume a daily dose of 0... more Italian public health authorities recommend women of childbearing age to assume a daily dose of 0.4 mg of folic acid (FA) from at least one month before conception in order to reduce the risk of having children affected by neural tube defects (NTDs). In this study, folate, homocysteine and vitamin B12 serum levels were determined in 77 women entering an in vitro fertilization program. About 75% of patients had serum folate values compatible with the intake of the recommended dose of FA for at least three months, whereas only the 61% of them reached or exceeded the serum folate concentration regarded as the optimal concentration during the periconceptional period. Mean vitamin B12 serum levels and mean homocysteine plasma levels resulted in normal range in all the women with mean values of 381.2 ± 2.2 pg/ml and 8.48 ± 2.2 lmol/l, respectively. In conclusion, only a portion of women entering an IVF program presents proper folate levels.

Research paper thumbnail of Teratology of valproic acid: an updated review of the possible mediating mechanisms

Minerva obstetrics and gynecology, May 1, 2018

Valproic acid (VPA) is an anti-epileptic drug (AED) which is currently being investigated for its... more Valproic acid (VPA) is an anti-epileptic drug (AED) which is currently being investigated for its potential application in the treatment of several types of cancers, including solid and non-solid tumor. It is well-known that prenatal exposure to VPA largely increases the risk for malformations and other developmental disorders. This review concentrates on clinical and experimental data on congenital anomalies attributed to maternal VPA exposure. Particular emphasis is placed on the potential mechanisms underlying VPA-induced malformations. Although several mechanisms have been suggested, there appears to be no data in the literature in support of a single definitive mechanism for VPA-exposure-related fetal malformations.

Research paper thumbnail of Editorial: Teratology and Reproductive Toxicology of Anticancer Agents

Anti-cancer Agents in Medicinal Chemistry, Sep 12, 2017

Research paper thumbnail of Fetal safety profile of aromatase inhibitors: Animal data

Reproductive Toxicology, Dec 1, 2016

Aromatase inhibitors (AIs) are a class of drugs that act by blocking the production of estrogens ... more Aromatase inhibitors (AIs) are a class of drugs that act by blocking the production of estrogens from androgens. The current review concentrates on the prenatal developmental toxicity of AIs in experimental models. Available data indicate that AIs may affect pregnancy at human therapeutic or lower doses. The window of vulnerability to AIs is not limited to organogenesis, but also includes the preimplantation stage and fetal periods. Decreased embryo/fetal survival was the prominent treatment-related effect. Morphological anomalies noted in fetuses exposed to AIs included skeletal anomalies, abnormal head morphology, increased ano-genital distance in female fetuses, and minor urinary tract system anomalies. Placental enlargement was consistently reported in rats and non-human primates after maternal treatment with several AIs. In conclusion, data from basic scientific research suggest that low intensity exposure to AIs applied during a wide gestational window can profoundly affect prenatal development.

Research paper thumbnail of Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization

Thrombosis Research, Jul 1, 2018

Research paper thumbnail of Ovotoxicity of cigarette smoke: A systematic review of the literature

Reproductive Toxicology, Sep 1, 2017

Highlights  Cigarette smoke negatively affects ovarian folliculogenesis.  The hypothesized caus... more Highlights  Cigarette smoke negatively affects ovarian folliculogenesis.  The hypothesized causes of ovarian damage include increased oxidative stress, increased cellular apoptosis or autophagy, DNA damage and abnormal crosstalk between oocyte and granulosa cells.

Research paper thumbnail of Nutrition, female fertility and in vitro fertilization outcomes

Reproductive Toxicology, Jun 1, 2023

Research paper thumbnail of In utero exposure to valproic acid during neurulation alters nitric oxide synthase isoforms expression

Reproductive Toxicology, Sep 1, 2016

Research paper thumbnail of Inhibition of nitric oxide synthesis causes pre-term delivery in the mouse

International journal of gynaecology and obstetrics, 2000

NO has been recently postulated as having a role in the complex molecular interplay which regulat... more NO has been recently postulated as having a role in the complex molecular interplay which regulates myometrial func-Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e tion during gestation (Norman, 1996; Sladek et al, 1997;

Research paper thumbnail of Thyroid autoimmunity and assisted reproductive technology (ART)

10th European Congress of Endocrinology, May 1, 2008

About 105 women (mean age 35.7+4.7) have been investigated; 11 subjects have been excluded from t... more About 105 women (mean age 35.7+4.7) have been investigated; 11 subjects have been excluded from the study because of known thyroid diseases. The remaining 95 women have been divided according to the cause of infertility; 34% were idiopathic, 26.6% had a male factor, 6.4% ...

Research paper thumbnail of Effect of vitamin D supplementation on uterine fibroids: a meta-analysis of the literature

Minerva obstetrics and gynecology, Apr 1, 2022

Research paper thumbnail of In Vivo Cigarette Smoke Exposure to Examine the Expression of Genes Involved in the Inflammatory Response in the Mouse Uterus

Current protocols, Jun 1, 2021

Cigarette smoke may impair uterine function, but the underlying mechanisms are poorly characteriz... more Cigarette smoke may impair uterine function, but the underlying mechanisms are poorly characterized. In this article, we describe the methodology for whole‐body exposure to cigarette smoke together with assessment of the impact of this exposure on the expression of a panel of genes related to stress and toxicity pathways in mouse uteri using an in vivo model. C57BL/6 mice are whole‐body‐exposed to three cigarettes daily, 7 days/week, for 2 months using a specific rodent ventilator. Uteri are then collected and subjected to qRT‐PCR analysis using the Stress & Toxicity PathwayFinder RT2 Profiler PCR Array (Qiagen). Cigarette smoke was found to be associated with an upregulation (≥2‐fold) of C‐reactive protein (Crp; 2.65‐fold, p‐value = 0.02), growth arrest and DNA‐damage‐inducible45γ (Gadd45γ; 2.11‐fold, p‐value = 0.04), interferon γ (Ifnγ; 2.05‐fold, p‐value = 0.01), and interleukin1α (Il1α; 7.74‐fold, p‐value = 0.003) and downregulation of matrix metallopeptidase‐9 (Mmp9; −2.42‐fold, p‐value = 0.01). The protocol used in this study may represent a new experimental model of mouse in vivo mainstream exposure to cigarette smoke. In addition, the resulting overexpression of pro‐inflammatory cytokines and genes involved in cell cycle proliferation, together with the downregulation of extracellular matrix metallopeptidases, may represent a toxicological response to cigarette smoke exposure, with potential repercussion for the processes of uterine remodeling and growth that are essential for uterine receptiveness. A recommendation to expand upon this research area is made. © 2021 Wiley Periodicals LLC.

Research paper thumbnail of MRAP2 regulates endometrial receptivity and function

Gene, Jun 1, 2019

A successful embryo implantation depends on the synchronization between a competent blastocyst an... more A successful embryo implantation depends on the synchronization between a competent blastocyst and a receptive endometrium. Recently, potential modulators of endometrial receptivity (OVGP1, MRAP2, ZCCHC12, and HAP1) have been reported likely with a functional role during embryo implantation. The aim of this study was to evaluate the gene expression of these genes in the endometrium of infertile women. Eighteen endometrial biopsies, during secretory lutheal phase, were recruited from women with unexplained infertility and women who cannot conceive due to their partners' fertility problems. qRT-PCR was carried out to evaluate MRAP2, OVGP1, ZCCHC12 and HAP1 gene expression. MRAP2 expression was also detected by western blot and it was localized by immunohistochemistry. Morphological analysis was performed by light microscopy. MRAP2 was significantly up-regulated in study vs. control group. Western blot analysis confirmed the observed MRAP2 up-expression. MRAP2 resulted mainly localized in the epithelial cells of uterine glands. Morphological analysis displayed that the epithelium of the uterine glands undergo hypertrophy in women with unexplained infertility in respect to women with male infertility factor. MRAP2 could be considered a mediator of endometrial receptivity likely acting on endometrial stability by binding to MCRs and PKR1.

Research paper thumbnail of An updated meta-analysis comparing the efficacy and safety of biosimilar medicinal products to the original follitropin alfa

Minerva Obstetrics and Gynecology

Research paper thumbnail of Profiling of mitochondrial heteroplasmy in single human oocytes by next‐generation sequencing

Molecular Reproduction and Development

Mitochondrial DNA (mtDNA) plays a crucial role in the development of a competent oocyte. Indeed, ... more Mitochondrial DNA (mtDNA) plays a crucial role in the development of a competent oocyte. Indeed, mtDNA alterations may predispose to chromosome nondisjunction, resulting in infertility due to a reduced vitality and quality of oocytes and embryos. In this methods paper, the multiple displacement amplification approach was applied in combination with next‐generation sequencing (NGS) to amplify and sequence, in single‐end, the entire mtDNA of single human oocytes to directly construct genomic NGS libraries, and subsequently, to highlight and quantify the mutations they presented. The bioinformatic workflow was carried out with a specific ad hoc developed in‐house software. This approach proved to be sensitive and specific, also highlighting the mutations present in heteroplasmy, showing deletion, insertion or substitution mutations in the genes involved in the respiratory chain, even if the found variants were benign or of uncertain meaning. The analysis of mtDNA mutations in the oocyte could provide a better understanding of specific genetic abnormalities and of their possible effect on oocyte developmental competence. This study shows how this approach, based on a massive parallel sequencing of clonally amplified DNA molecules, allows to sequence the entire mitochondrial genome of single oocytes in a short time and with a single analytical run and to verify mtDNA mutations.