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1.
BMC Pharmacol Toxicol ; 25(1): 42, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010179

ABSTRACT

BACKGROUND: A global increase in cannabis use has led to questions about its effects on fertility. The rise in consumption amongst women of reproductive age is a growing concern, as this group is vulnerable in terms of reproductive health. Ample evidence suggests that the psychoactive component of cannabis, Δ9-Tetrahydrocannabinol (THC), interacts with the endocannabinoid system (ECS), that helps regulate mammalian reproduction. This study aimed to research the epigenetic effects of THC in bovine granulosa cells (GCs) by (1) investigating global DNA methylation via measuring 5-mC and 5-hmC levels; (2) measuring key methylation regulators, including the methylating enzymes DNMT1, DNMT3a, DNMT3b and the demethylases TDG and TET1/2/3; and (3) assessing fertility-associated miRNAs key in developmental competency, including miR-21, -155, -33b, -324 and -346. METHODS: Bovine GCs were used as a translational model for reproductive toxicity in humans. To determine THC effects, GCs were isolated from Cumulus-Oocyte-Complexes (COCs) from bovine ovaries, cultured in vitro for 7 days, or until confluent, and cryopreserved at passage 1 (P1). For experimentation, cells were thawed, cultured until passage 2 (P2), serum restricted for 24-h and treated for 24-h in one of five groups: control, vehicle (1:1:18 ethanol: tween: saline) and three clinically relevant THC doses (0.032, 0.32 and 3.2 µM). Global methylation was assessed by measuring 5-mC and 5-hmC levels with flow cytometry. To assess mRNA and protein expression of methylation regulators and miRNA profiles, qPCR and Western Blotting were utilized. Shapiro-Wilk test was used to determine normality within datasets. One-way ANOVA was applied to determine statistical significance using GraphPad Prism 6.0.0. RESULTS: Results indicate a significant decrease (p = 0.0435) in 5-mC levels following low THC exposure, while no changes were observed in 5-hmC levels. A significant increase in DNMT1 following high THC exposure at the RNA level (p < 0.05) and a significant increase following low THC exposure at the protein level (p = 0.0048) were also observed. No significant differences were observed in DNMT3a/3b, TDG, TET1/2/3 mRNAs or in any of the miRNAs analyzed. CONCLUSIONS: This research suggests that THC mainly affects DNA methylation, but not miRNA profiles, ultimately altering gene expression and likely impairing oocyte competence, maturation, and fertilization potential.


Subject(s)
DNA Methylation , Dronabinol , Granulosa Cells , MicroRNAs , Animals , Female , Cattle , MicroRNAs/genetics , Dronabinol/pharmacology , Granulosa Cells/drug effects , Granulosa Cells/metabolism , DNA Methylation/drug effects , Cells, Cultured
2.
Biomedicines ; 12(1)2024 Jan 21.
Article in English | MEDLINE | ID: mdl-38275408

ABSTRACT

Higher levels of bisphenols are found in granulosa cells of women with polycystic ovary syndrome (PCOS), posing the question: Is bisphenol exposure linked to PCOS pathophysiology? Human granulosa cells were obtained from women with and without PCOS, and genes and microRNAs associated with PCOS were investigated. The first phase compared healthy women and those with PCOS, revealing distinct patterns: PCOS subjects had lower 11ß-HSD1 (p = 0.0217) and CYP11A1 (p = 0.0114) levels and elevated miR-21 expression (p = 0.02535), elucidating the molecular landscape of PCOS, and emphasizing key players in its pathogenesis. The second phase focused on healthy women, examining the impact of bisphenols (BPA, BPS, BPF) on the same genes. Results revealed alterations in gene expression profiles, with BPS exposure increasing 11ß-HSD1 (p = 0.02821) and miR-21 (p = 0.01515) expression, with the latest mirroring patterns in women with PCOS. BPA exposure led to elevated androgen receptor (AR) expression (p = 0.0298), while BPF exposure was associated with higher levels of miR-155. Of particular interest was the parallel epigenetic expression profile between BPS and PCOS, suggesting a potential link. These results contribute valuable insights into the nuanced impact of bisphenol exposure on granulosa cell genes, allowing the study to speculate potential shared mechanisms with the pathophysiology of PCOS.

3.
J Obstet Gynaecol Can ; 46(5): 102361, 2024 May.
Article in English | MEDLINE | ID: mdl-38272217

ABSTRACT

OBJECTIVE: To assess the potential costs and benefits of preimplantation genetic testing for aneuploidy (PGT-A) across age groups, considering financial costs, total euploidy rates and the potential for morphology grading to predict a euploid embryo. METHODS: This study is a blinded retrospective chart review of patients who incorporated PGT-A as part of their in vitro fertilization (IVF) treatment cycle at a university-affiliated fertility clinic. Patients between 25-44 years of age undergoing IVF with intracytoplasmic sperm injection and PGT-A with autologous oocytes (n = 220) were included in this study. Number of blastocysts achieved, euploidy rates and PGT-A costs were compared between 3 age groups: <35 years, 35-37, and ≥38. Additionally, agreement on the top-quality embryo based on morphology assessment alone versus PGT-A selection was analyzed and further compared based on the number of blastocysts achieved. RESULTS: A significant negative correlation between patient age and number of embryos produced, PGT-A costs, and euploidy rates (P < 0.001) was observed. Additionally, morphology alone ratings were able to predict the top-quality euploid embryo 78% of the time in the <35 age group, but only 32% of the time in the ≥38 age group (P < 0.05), with a trend toward even lower agreement when 3 or fewer blastocysts were produced. CONCLUSION: Based on our cost analysis, it may be advantageous to incorporate PGT-A when maternal age is ≥38, given the lower financial costs associated with each cycle and the low likelihood of transferring a euploid embryo on the first attempt for this age group. Nevertheless, we acknowledge that PGT-A remains a complex decision influenced by a multitude of factors.


Subject(s)
Aneuploidy , Cost-Benefit Analysis , Preimplantation Diagnosis , Humans , Preimplantation Diagnosis/economics , Female , Adult , Retrospective Studies , Fertilization in Vitro/economics , Age Factors , Canada , Pregnancy , Genetic Testing/economics , Sperm Injections, Intracytoplasmic/economics
4.
BMC Mol Cell Biol ; 24(1): 6, 2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36823609

ABSTRACT

BACKGROUND: Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment. RESULTS: Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p < 0.05) compared to control and vehicle group sperm. Transcriptome analysis revealed that 39 genes were found to be differentially expressed by 0.032µM THC exposure, 196 genes were differentially expressed by 0.32µM THC exposure, and 33 genes were differentially expressed by 3.2µM THC. Secondary analysis reveals pathways involving development, nucleosomes, ribosomes and translation, and cellular metabolism to be significantly enriched. CONCLUSION: Phytocannabinoid exposure to sperm may adversely affect sperm function by stimulating premature capacitation. These findings also show for the first time that spermatozoal transcripts may be altered by THC exposure. These results add to previous research demonstrating the molecular effects of cannabinoids on sperm and warrant further research into the effects of cannabis on male fertility.


Subject(s)
Cannabinoids , Dronabinol , Male , Animals , Cattle , Humans , Adult , Dronabinol/pharmacology , Dronabinol/metabolism , Sperm Capacitation , Semen , Cannabinoids/metabolism , Cannabinoids/pharmacology , Spermatozoa/metabolism
5.
Anim Reprod Sci ; 186: 85-92, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28969874

ABSTRACT

Anti-Mullerian hormone (AMH) is expressed by both male and female fetuses during mammalian development, with males expressing AMH earlier and at significantly higher concentration. The aim of the current study was to explore the potential impact of pregnancy and fetal sex on maternal AMH and to determine if plasma (Pl) AMH or placenta intercotyledonary membrane and cotyledonary AMH receptor 2 (AMHR2) mRNA expression differ in pregnant cows carrying male vs. female fetuses. AMH levels in blood were measured using a bovine optimized ELISA kit. Cows pregnant with a male fetus were observed to have a significantly greater difference in Pl AMH between day 35 and 135 of gestation. Average fetal AMH level between 54 and 220days of gestation was also observed to be significantly higher in male vs. female fetuses. Intercotyledonary membranes and cotyledons were found to express AMHR2 between days 38 and 80 of gestation at similar levels in both fetal sexes. These findings support the hypothesis that fetal sex alters maternal Pl AMH during pregnancy in cattle.


Subject(s)
Anti-Mullerian Hormone/metabolism , Cattle/blood , Fetus/physiology , Pregnancy, Animal , Animals , Anti-Mullerian Hormone/blood , Cattle/physiology , Female , Male , Maternal-Fetal Exchange/physiology , Placenta/metabolism , Pregnancy , Pregnancy, Animal/blood
6.
Anim Reprod Sci ; 167: 51-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26898391

ABSTRACT

This study was conducted to evaluate plasma anti-Mullerian hormone (Pl AMH), follicular fluid AMH (FF AMH) and granulosa cell AMH transcript (GC AMH) levels and their relationships with reproductive parameters in two cattle subspecies, Bos taurus indicus (Zebu), and Bos taurus taurus (European type cattle). Two-dimensional ultrasound examination and serum collection were performed on Zebu, European type and crossbreed cows to determine antral follicle count (AFC), ovary diameter (OD) and Pl AMH concentration. Slaughterhouse ovaries for Zebu and European type cattle were collected to determine FF AMH concentrations, GC AMH RNA levels, AFC, oocyte number, cleavage and blastocyst rate. Additionally GC AMH receptor 2 (AMHR2) RNA level was measured for European type cattle. Relationship between AMH and reproductive parameters was found to be significantly greater in Zebu compared to European cattle. Average Pl AMH mean ± SE for Zebu and European cattle was 0.77 ± 0.09 and 0.33 ± 0.24 ng/ml respectively (p = 0.01), whereas average antral FF AMH mean ± SE for Zebu and European cattle was 4934.3 ± 568.5 and 2977.9 ± 214.1 ng/ml respectively (p < 0.05). This is the first published report of FF and GC AMH in Zebu cattle. Levels of GC AMHR2 RNA in European cattle were correlated to oocyte number (p = 0.01). Crossbred animals were found more similar to their maternal Zebu counterparts with respect to their Pl AMH to AFC and OD relationships. These results demonstrate that AMH reflects differences between reproduction potential of the two cattle subspecies therefore can potentially be used as a reproductive marker. Furthermore these results reinforce the importance of separately considering the genetic backgrounds of animals when collecting or interpreting bovine AMH data for reproductive performance.


Subject(s)
Anti-Mullerian Hormone/metabolism , Cattle/physiology , Granulosa Cells/metabolism , Reproduction/physiology , Animals , Cattle/genetics , Cattle/metabolism , Female , Follicular Fluid/chemistry , Gene Expression Regulation/physiology , Reproduction/genetics
7.
Fertil Steril ; 105(3): 684-689, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26690006

ABSTRACT

OBJECTIVE: To determine the effectiveness of education provided by health care professionals during and after IVF treatment in preparing couples for surplus embryo disposition decisions. DESIGN: Cross-sectional survey. SETTING: University-affiliated fertility center. PATIENT(S): Couples with embryos cryopreserved for more than 2 years. INTERVENTION(S): Self-administered questionnaire. MAIN OUTCOME MEASURE(S): A Likert scale was used to rate the response to questions about patients' preparedness to make decisions regarding their surplus embryos. RESULT(S): The survey response rate was 70% (131 of 187). Education provided by health care professionals before initiating treatment met the needs of the majority of participants (n = 86). After treatment, the education received was not adequate to assist couples in making embryo disposition decisions. Of the 127 respondents who provided feedback on their intention for their cryopreserved embryos, 37% (n = 47) had no intention of using cryopreserved embryos for their own reproduction, 24% (n = 30) intended to use embryos for procreation, and the remaining 39% (n = 50) remained undecided regarding their future use of their embryos. Participants with more than 3 years of infertility (n = 49) were most likely to feel conflicted about the decision after treatment. CONCLUSION(S): The education received after treatment was considered inadequate. Couples with a long duration of infertility and those conflicted about final embryo disposition may be appropriate targets for further intervention. More written information and/or counseling services after treatment may help patients make informed and timely decisions regarding their surplus embryos.


Subject(s)
Counseling , Cryopreservation , Embryo Disposition/psychology , Fertilization in Vitro , Health Knowledge, Attitudes, Practice , Infertility/therapy , Patient Education as Topic , Adult , Choice Behavior , Conflict, Psychological , Cross-Sectional Studies , Female , Fertility , Health Care Surveys , Humans , Infertility/diagnosis , Infertility/physiopathology , Infertility/psychology , Male , Middle Aged , Perception , Surveys and Questionnaires , Time Factors
8.
Reprod Biomed Online ; 22(1): 17-24, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21115268

ABSTRACT

Brain-derived neurotrophic factor (BDNF) is thought to play a role in follicle activation and oocyte maturation. It is postulated that BDNF and its receptor, tyrosine kinase receptor B (TrkB), may also play a role in maintaining the corpus luteum. Therefore,human granulosa lutein cells (GLC) were obtained from women undergoing ovulation induction and treated with increasing concentrations of cAMP (0, 125, 500 and 1000 µmol/l). BDNF and progesterone concentrations were quantified by enzyme-linked immunosorbent assay. cAMP treatment significantly increased progesterone output but had no effect on BDNF concentration in the spent media. However, the BDNF concentration was significantly increased in GLC lysates. To assess the expression of BDNF and TrkB in active versus regressing corpora lutea, ovaries from adult female BALBc mice (n = 4) from each day of the oestrous cycle were processed for immunohistochemistry. Two markers of luteal activity were used (3b-hydroxysteroid dehydrogenase and tenascin-X). There was a trend towards higher BDNF and TrkB H-scores in active versus regressing corpus lutea. In conclusion, intracellular BNDF concentrations were dose-dependently increased by cAMP but treatments had no effect on BDNF output. It is speculated that BDNF contributes in an autocrine manner to GLC survival in the active corpus luteum.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Luteal Cells/metabolism , 3-Hydroxysteroid Dehydrogenases/metabolism , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Animals , Cells, Cultured , Cyclic AMP/metabolism , Estrous Cycle/metabolism , Female , Humans , Mice , Mice, Inbred BALB C , Osmolar Concentration , Ovary/cytology , Ovary/metabolism , Ovulation Induction , Progesterone/metabolism , Receptor, trkB/metabolism , Tenascin/metabolism
9.
Reprod Biomed Online ; 21(1): 100-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20466593

ABSTRACT

It has been shown that benzo[a]pyrene, a key component of cigarette smoke and an aryl hydrocarbon receptor (AhR) ligand, reduced growth of isolated rat follicles in vitro. However, the mechanism underlying the induced changes in folliculogenesis is unknown. This study proposed that the reported adverse effects of benzo[a]pyrene on follicle growth are mediated through AhR activation. The objective was to investigate the effect of benzo[a]pyrene with and without AhR antagonists (resveratrol or 3',4'-dimethoxyflavone (3,4-DMF)) on follicle growth, oestradiol output, anti-Müllerian hormone (AMH) concentration and cell proliferation in isolated rat follicles cultured in vitro. Benzo[a]pyrene treatment significantly inhibited follicle growth and cell proliferation at concentrations of 1.5 ng/ml and higher (P < 0.05), an effect attenuated by co-incubation with benzo[a]pyrene and resveratrol or 3,4-DMF. A significant decrease in oestradiol (P < 0.05) and AMH output (P < 0.001) by cultured follicles was induced by benzo[a]pyrene treatment, an effect attenuated by co-incubation with 3,4-DMF. The results suggest that the adverse effects of benzo[a]pyrene on follicle growth, steroidogenesis and AMH output are mediated through activation of the AhR. Moreover, AhR antagonists such as resveratrol and 3,4-DMF may have therapeutic benefit in protecting the ovary against the adverse effects of AhR ligands, including benzo[a]pyrene.


Subject(s)
Benzo(a)pyrene/toxicity , Flavones/pharmacology , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Receptors, Aryl Hydrocarbon/antagonists & inhibitors , Stilbenes/pharmacology , Animals , Anti-Mullerian Hormone/metabolism , Cells, Cultured , Estradiol/metabolism , Female , Rats , Rats, Wistar , Resveratrol
10.
Int J Nurs Pract ; 15(4): 311-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19703048

ABSTRACT

Cancer treatment and the field of reproductive technology have each made impressive advancements in the last decade. Improved cancer treatment and survival rates have increased the number of cancer survivors, who might benefit from an array of fertility preservation strategies provided by emerging and advanced assisted conception technology. The challenge becomes bridging the gap between these two separate disciplines to ultimately improve the quality of life for cancer survivors. This paper discusses the issues and process involved with bringing these two teams of health-care professionals together. This model provides a framework for coordinating efforts in providing fertility preservation options to patients undergoing treatment for cancer. Effective multidisciplinary teams that include: oncologists, nurses in the specialties of oncology and infertility, social workers, reproductive endocrinology and infertility specialists, andrologists, and embryologists are required to work together in order to achieve success. The result of this unique team approach is not only a cancer survivor, but one whose quality of life might be enhanced by being able to have a child of his or her own in the future.


Subject(s)
Cooperative Behavior , Fertility , Neoplasms/physiopathology , Patient Care Team , Adolescent , Adult , Female , Humans , Male , Quality of Life , Survivors , Young Adult
12.
Reprod Toxicol ; 25(4): 420-5, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18585891

ABSTRACT

Bisphenol A (BPA) is an estrogenic contaminant that has been quantified at higher levels in the follicular fluid of women with polycystic ovarian syndrome (PCOS) compared to healthy fertile controls. However, the effect of BPA on granulosa cell function is unknown. Therefore, the objective of the present study was to quantify the effect of BPA on granulosa cell progesterone (P4) output and matrix metalloproteinase (MMP)-2, and -9 output and activity. Granulosa-lutein cells (GLCs) were collected from women undergoing oocyte retrieval in an academic in vitro fertilization (IVF) program. Granulosa-lutein cells were treated with increasing log concentrations of BPA (1-10,000 ng/ml) or 17beta-estradiol (E2, 272 pg/ml or 1.0 nM) and treatment effects on MMP-2 and -9 activity and output, cell viability and cell proliferation were measured by commercial gelatin zymography, MMP-ELISA, MTS and BrdU incorporation assays, respectively. Granulosa-lutein cells in culture secrete MMP-2 and MMP-9. Bisphenol A treatment concentration-dependently increased MMP-9 output by GLCs with a maximal effect observed at 1000 ng/ml. Cell viability/proliferation was unaffected by BPA treatment at concentrations

Subject(s)
Environmental Pollutants/toxicity , Estrogens, Non-Steroidal/toxicity , Luteal Cells/drug effects , Matrix Metalloproteinase 9/metabolism , Phenols/toxicity , Adult , Benzhydryl Compounds , Cell Survival/drug effects , Cells, Cultured , Female , Humans , Luteal Cells/enzymology , Matrix Metalloproteinase 2/metabolism
13.
J Toxicol Environ Health B Crit Rev ; 11(3-4): 162-76, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18368551

ABSTRACT

Throughout the 1980s and 1990s the crude human birth rate (live births per 1000 population) declined, indicating reduced fertility and suggesting a potential decline in fecundity (the potential to conceive). Detection of environmental contaminants in human tissues, together with reports of a global decline in semen quality, further fueled speculation that human infertility rates are increasing and environmental toxicants are potentially important causal agents associated with this change. However, there is little compelling evidence to suggest that infertility rates amongst the general population have changed over time. Moreover, recent studies suggest a rise in the fertility rates. While several studies documented increased time to pregnancy (TTP) in exposed study populations, other investigators were not able to replicate these findings. Nevertheless, studies involving occupational exposure together with results from animal experiments lend support to the conclusion that environmental contaminants potentially adversely affect fertility. Consequently, the impact of exposure to environmental contaminants on human fertility remains controversial. To test the hypothesis that environmental contaminant exposure was associated with enhanced risk of infertility, data concerning trends in fertility and infertility rates were examined to assess the impact of exposure of developing gametes to environmental contaminants. The relationship between exposure and reproductive outcomes was then examined to illustrate the range of adverse effects for reproductive toxicants with data sets of divergent depth and reliability. Data showed that only a weak association between exposure to environmental contaminants and adverse effects on human fertility exists. However, it is postulated that evidence of chemical exposure and potential health consequences of these exposures highlight the need for further research in this area.


Subject(s)
Endocrine Disruptors/adverse effects , Environmental Exposure/adverse effects , Infertility/chemically induced , Benzhydryl Compounds , Canada/epidemiology , Environmental Monitoring , Epidemiological Monitoring , Female , Humans , Infertility/epidemiology , Male , Pesticides/adverse effects , Phenols/adverse effects , Tobacco Smoke Pollution/adverse effects
14.
J Obstet Gynaecol Can ; 30(2): 138-142, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18254995

ABSTRACT

OBJECTIVE: We wished to investigate the aromatase activity (AA) of granulosa cells (GCs) in women undergoing ovarian follicular stimulation for in vitro fertilization (IVF). METHODS: Granulosa cells were harvested from follicular fluid aspirated at the time of oocyte retrieval in women undergoing IVF. Data related to the follicular stimulation and IVF were collected by chart review. We conducted a retrospective analysis of the relation between the response to stimulation and the AA of GCs obtained from IVF patients. We assessed the response to stimulation by calculation of the area under the curve (AUC) of the monitored serum estradiol levels, and divided patients into "poor responders" and "good responders." RESULTS: There was no difference in AA between women with a poor response to stimulation and women with a good response. Implantation rates and pregnancy rates were significantly lower in poor responders (5.3% and 9.1% respectively) than in good responders (19.7% and 54.8% respectively), even though embryo quality was similar in each group. CONCLUSIONS: Women who have a poor response to ovarian follicular stimulation preceding IVF have lower pregnancy rates than women with a good response. The lower pregnancy rates do not appear to be a consequence of an abnormal follicular environment, because AA and the ratio of serum estradiol AUC to oocytes retrieved was similar in both groups of women.


Subject(s)
Aromatase/physiology , Estradiol/blood , Fertilization in Vitro , Granulosa Cells/enzymology , Ovulation Induction/methods , Female , Humans , Retrospective Studies , Treatment Outcome
15.
Reprod Toxicol ; 25(1): 100-6, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18065195

ABSTRACT

Cigarette smoking is a well-established reproductive hazard that has been linked with decreased fertility in both smokers and those exposed to second hand smoke. The chemical components responsible for the reproductive toxic effects of cigarette smoke are unknown. Moreover, exposure of reproductive tissues to the chemical constituents of cigarette smoke is largely unknown. Therefore, we measured the levels of benzo[a]pyrene (B[a]P), and other polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke, in the serum and follicular fluid of women exposed to mainstream (n=19) and side stream smoke (n=7) compared to non-smokers (n=10). Women exposed to mainstream smoke had significantly higher levels of B[a]P (1.32+/-0.68ng/ml) in their follicular fluid compared to side stream exposed (0.05+/-0.01ng/ml) or their non-smoking (0.03+/-0.01ng/ml) counterparts. More importantly we found significantly higher (p<0.001) levels of B[a]P in the follicular fluid of women who did not conceive (1.79+/-0.03ng/ml) compared to those that achieved a pregnancy (0.08+/-0.03ng/ml). Other PAHs known to be present in cigarette smoke were also detectable in both serum and follicular fluid of study subjects studied but with lower frequency compared to B[a]P and no differences in serum or follicular fluid levels between the groups could be demonstrated. The important finding that B[a]P reaches the follicular fluid and the fact that it is found at much higher levels in women who smoke provides further evidence that of the many toxicants present in cigarette smoke, B[a]P may be a key compound that is central to the documented adverse effects of cigarette smoke on follicular development and subsequent fertility.


Subject(s)
Benzo(a)pyrene/analysis , Follicular Fluid/chemistry , Infertility/etiology , Polycyclic Aromatic Hydrocarbons/analysis , Smoking/metabolism , Tobacco Smoke Pollution/adverse effects , Adult , Benzo(a)pyrene/toxicity , Case-Control Studies , Female , Fertilization in Vitro , Humans , Infertility/blood , Infertility/metabolism , Infertility/physiopathology , Infertility/therapy , Polycyclic Aromatic Hydrocarbons/blood , Polycyclic Aromatic Hydrocarbons/toxicity , Pregnancy , Pregnancy Rate , Reproduction/drug effects , Smoking/adverse effects , Smoking/blood , Surveys and Questionnaires , Treatment Outcome
16.
Cancer ; 110(5): 1125-9, 2007 Sep 01.
Article in English | MEDLINE | ID: mdl-17647219

ABSTRACT

BACKGROUND: Improving success in the treatment of cancer has resulted in an increasing number of survivors. An important quality of life issue among younger survivors is the ability to have a family. Current gonadotoxic treatments for cancer pose a challenge to future fertility. Preservation of fertility after gonadotoxic therapy is an important consideration for these patients. In a regional center, the authors evaluated efficacy and utilization of sperm banking for preservation of male fertility in adolescents and young adults (AYA) with cancer. METHODS: A retrospective chart review was conducted to obtain data on clinical features, andrology, and fertility from patients (ages < 30 years) who cryopreserved samples of semen from 1995-2005. RESULTS: Of 821 newly diagnosed male AYA cancer patients, aged 14-30 years, only 146 (17.8%) used sperm cryopreservation technology. Patients who used their cryopreserved semen for attempted conception had a 36.4% success rate with intrauterine insemination (IUI) and a 50.0% clinical pregnancy rate with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). CONCLUSIONS: Sperm cryopreservation by AYA males with cancer is an efficacious method for preserving future fertility. Awareness and employment of assisted reproductive technologies needs to be implemented by an interdisciplinary team of experts caring for these patients and can result in successful paternity in males after treatment for cancer.


Subject(s)
Neoplasms/pathology , Sperm Banks/methods , Adolescent , Adult , Female , Fertilization in Vitro/statistics & numerical data , Humans , Infertility, Male/etiology , Infertility, Male/physiopathology , Insemination, Artificial/statistics & numerical data , Male , Neoplasms/complications , Pregnancy , Reproducibility of Results , Semen/cytology , Semen/physiology , Sperm Injections, Intracytoplasmic/statistics & numerical data
17.
Hum Reprod ; 22(4): 961-7, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17218370

ABSTRACT

BACKGROUND: The adverse effects of cigarette smoking on human fertility have been well documented. However, the mechanism(s) underlying the detrimental effects of cigarette smoking are unknown. Using a novel isolated rat follicle culture assay, we tested the hypothesis that benzo-[a]-pyrene (B[a]P), a constituent of cigarette smoke, can inhibit follicle growth. METHODS: B[a]P levels were quantified in the serum and follicular fluid (FF) of women undergoing in vitro fertilization (IVF) treatment exposed to mainstream smoke (n = 19) and non-smokers (n = 10) by gas chromatography mass spectrometry. Isolated rat follicles were cultured with increasing concentrations of B[a]P (1.5-300 ng ml(-1)) and follicle diameter was measured daily. RESULTS: Mean ( +/- Standard error of the mean) B[a]P) was quantified in the serum (0.40 +/- 0.13 ng ml(-1)) and FF (1.32 +/- 0.68 ng ml(-1)) of women who smoke. IVF stimulation and outcome measures were similar between female smokers and non-smokers with the exception of implantation rate and pregnancy rate, which were both significantly lower (P < 0.05) in the MS group. B[a]P treatment significantly reduced rat follicle diameter and attenuated FSH stimulated growth in a dose-dependent manner, beginning at 1.5 ng ml(-1). CONCLUSIONS: Our data suggest that B[a]P, at levels representative of those measured in human FF, may adversely affect follicle development and be an ovarian toxicant.


Subject(s)
Benzo(a)pyrene/toxicity , Cells, Cultured/drug effects , Fertility/drug effects , Ovarian Follicle/drug effects , Smoking/adverse effects , Adult , Animals , Female , Fertilization in Vitro , Gas Chromatography-Mass Spectrometry , Humans , Ovarian Follicle/growth & development , Ovary/drug effects , Rats , Treatment Outcome
18.
Hum Reprod ; 20(9): 2531-5, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15919779

ABSTRACT

BACKGROUND: Cigarette smoking (CS) is a widely recognized health hazard, yet it remains prevalent in society and the effects of environmental tobacco smoke exposure on fertility are unknown. Our objective was to measure the effects of CS on the fertility of mainstream (MS) or sidestream (SS) smoke-exposed women compared to their non-smoking (NS) counterparts. METHODS: This retrospective study investigated 225 female patients undergoing IVF (n = 97) or ICSI (n = 128). Patients were grouped based on their smoking status for comparison. This included: 39 MS (18 IVF and 21 ICSI); 40 SS (16 IVF and 24 ICSI); and 146 NS (63 IVF and 83 ICSI) women. Fertility treatment outcomes including embryo quality, implantation and pregnancy rate were measured. RESULTS: No difference in embryo quality between the three groups was observed. However, there was a significant difference in implantation rate (MS = 12.0%, SS = 12.6%, and NS = 25.0%) and pregnancy rate (MS = 19.4%, SS = 20.0%, and NS = 48.3%) per embryo transfer. CONCLUSIONS: Despite similar embryo quality there was a striking difference in implantation and pregnancy rates of MS and SS smokers when compared with NS. Our data demonstrate that the effects of SS smoking are equally as damaging as MS smoke on fertility.


Subject(s)
Fertilization in Vitro/statistics & numerical data , Infertility, Female/epidemiology , Pregnancy Outcome/epidemiology , Smoking/adverse effects , Tobacco Smoke Pollution/adverse effects , Embryo Implantation , Female , Humans , Infertility, Female/therapy , Pregnancy , Prevalence , Retrospective Studies
19.
Fertil Steril ; 77(4): 844-5, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11937146

ABSTRACT

OBJECTIVE: To determine the cause of infertility in a couple whose oocytes failed to mature in two consecutive fertility treatments. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 32-year-old woman with unexplained infertility. INTERVENTION(S): Cytogenetic evaluation of oocytes that failed to reach meiotic metaphase II stage of maturation. MAIN OUTCOME MEASURE(S): Observation of oocyte maturity and chromosome composition after fixing and staining with Orcein stain. RESULT(S): Cytogenetic analysis revealed that the oocytes had successfully resumed meiosis. Germinal vesicle breakdown was also indicated, and chromosomes were at metaphase II stage of development. However, meiotic reduction of those chromosomes failed. CONCLUSION(S): Infertility in this couple seems to be attributed to the failure of the chromosomes to complete the reduction phase of metaphase II of meiosis.


Subject(s)
Cytogenetic Analysis , Infertility/genetics , Meiosis , Oocytes/ultrastructure , Adult , Cells, Cultured , Chromosomes/ultrastructure , Female , Fertilization in Vitro , Humans , Male , Metaphase
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