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Article ; Online: Perfluoroalkyl Chemicals and Male Reproductive Health: Do PFOA and PFOS Increase Risk for Male Infertility?

Tarapore, Pheruza / Ouyang, Bin

International journal of environmental research and public health

2021 Volume 18, Issue 7

Abstract: Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence ... ...

Abstract	Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence linking PFAS exposure to health effects, an issue of concern since PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) bioaccumulate in humans, with a half-life of years. Many epidemiological studies suggest that, worldwide, semen quality has decreased over the past several decades. One of the most worrying effects of PFOS and PFOA is their associations with lower testosterone levels, similar to clinical observations in infertile men. This review thus focuses on PFOS/PFOA-associated effects on male reproductive health. The sources of PFAS in drinking water are listed. The current epidemiological studies linking increased exposure to PFAS with lowered testosterone and semen quality, and evidence from rodent studies supporting their function as endocrine disruptors on the reproductive system, exhibiting non-monotonic dose responses, are noted. Finally, their mechanisms of action and possible toxic effects on the Leydig, Sertoli, and germ cells are discussed. Future research efforts must consider utilizing better human model systems for exposure, using more accurate PFAS exposure susceptibility windows, and improvements in statistical modeling of data to account for the endocrine disruptor properties of PFAS.
MeSH term(s)	Alkanesulfonic Acids/toxicity ; Caprylates/toxicity ; Environmental Pollutants/toxicity ; Fluorocarbons/toxicity ; Humans ; Infertility, Male/chemically induced ; Infertility, Male/epidemiology ; Male ; Reproductive Health ; Semen Analysis
Chemical Substances	Alkanesulfonic Acids ; Caprylates ; Environmental Pollutants ; Fluorocarbons ; perfluorooctanoic acid (947VD76D3L) ; perfluorooctane sulfonic acid (9H2MAI21CL)
Language	English
Publishing date	2021-04-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph18073794
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Perfluoroalkyl Chemicals and Male Reproductive Health

Pheruza Tarapore / Bin Ouyang

International Journal of Environmental Research and Public Health, Vol 18, Iss 3794, p

Do PFOA and PFOS Increase Risk for Male Infertility?

2021 Volume 3794

Abstract	Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence linking PFAS exposure to health effects, an issue of concern since PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) bioaccumulate in humans, with a half-life of years. Many epidemiological studies suggest that, worldwide, semen quality has decreased over the past several decades. One of the most worrying effects of PFOS and PFOA is their associations with lower testosterone levels, similar to clinical observations in infertile men. This review thus focuses on PFOS/PFOA-associated effects on male reproductive health. The sources of PFAS in drinking water are listed. The current epidemiological studies linking increased exposure to PFAS with lowered testosterone and semen quality, and evidence from rodent studies supporting their function as endocrine disruptors on the reproductive system, exhibiting non-monotonic dose responses, are noted. Finally, their mechanisms of action and possible toxic effects on the Leydig, Sertoli, and germ cells are discussed. Future research efforts must consider utilizing better human model systems for exposure, using more accurate PFAS exposure susceptibility windows, and improvements in statistical modeling of data to account for the endocrine disruptor properties of PFAS.
Keywords	PFOA ; PFOS ; perfluorooctanoate ; perfluorooctane sulfonate ; testosterone ; spermatogenesis ; Medicine ; R
Subject code	333
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel assay to measure low-density lipoproteins binding to proteoglycans.

Geh, Esmond N / Swertfeger, Debi K / Sexmith, Hannah / Heink, Anna / Tarapore, Pheruza / Melchior, John T / Davidson, W Sean / Shah, Amy Sanghavi

PloS one

2024 Volume 19, Issue 1, Page(s) e0291632

Abstract: Background: The binding of low-density lipoprotein (LDL) to proteoglycans (PGs) in the extracellular matrix (ECM) of the arterial intima is a key initial step in the development of atherosclerosis. Although many techniques have been developed to assess ... ...

Abstract	Background: The binding of low-density lipoprotein (LDL) to proteoglycans (PGs) in the extracellular matrix (ECM) of the arterial intima is a key initial step in the development of atherosclerosis. Although many techniques have been developed to assess this binding, most of the methods are labor-intensive and technically challenging to standardize across research laboratories. Thus, sensitive, and reproducible assay to detect LDL binding to PGs is needed to screen clinical populations for atherosclerosis risk. Objectives: The aim of this study was to develop a quantitative, and reproducible assay to evaluate the affinity of LDL towards PGs and to replicate previously published results on LDL-PG binding. Methods: Immunofluorescence microscopy was performed to visualize the binding of LDL to PGs using mouse vascular smooth muscle (MOVAS) cells. An in-cell ELISA (ICE) was also developed and optimized to quantitatively measure LDL-PG binding using fixed MOVAS cells cultured in a 96-well format. Results: We used the ICE assay to show that, despite equal APOB concentrations, LDL isolated from adults with cardiovascular disease bound to PG to a greater extent than LDL isolated from adults without cardiovascular disease (p<0.05). Conclusion: We have developed an LDL-PG binding assay that is capable of detecting differences in PG binding affinities despite equal APOB concentrations. Future work will focus on candidate apolipoproteins that enhance or diminish this interaction.
MeSH term(s)	Animals ; Mice ; Lipoproteins, LDL/metabolism ; Proteoglycans/metabolism ; Cardiovascular Diseases ; Atherosclerosis ; Apolipoproteins B/metabolism ; Protein Binding
Chemical Substances	Lipoproteins, LDL ; Proteoglycans ; Apolipoproteins B
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0291632
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Three-Generation Study of Male Rats Gestationally Exposed to High Butterfat and Bisphenol A: Impaired Spermatogenesis, Penetrance with Reduced Severity

Ho, Shuk-Mei / Rao, Rahul / Ouyang, Bin / Tam, Neville N. C. / Schoch, Emma / Song, Dan / Ying, Jun / Leung, Yuet-Kin / Govindarajah, Vinothini / Tarapore, Pheruza

Nutrients. 2021 Oct. 17, v. 13, no. 10

2021

Abstract: Gestational high butterfat (HFB) and/or endocrine disruptor exposure was previously found to disrupt spermatogenesis in adulthood. This study addresses the data gap in our knowledge regarding transgenerational transmission of the disruptive interaction ... ...

Abstract	Gestational high butterfat (HFB) and/or endocrine disruptor exposure was previously found to disrupt spermatogenesis in adulthood. This study addresses the data gap in our knowledge regarding transgenerational transmission of the disruptive interaction between a high-fat diet and endocrine disruptor bisphenol A (BPA). F0 generation Sprague-Dawley rats were fed diets containing butterfat (10 kcal%) and high in butterfat (39 kcal%, HFB) with or without BPA (25 µg/kg body weight/day) during mating and pregnancy. Gestationally exposed F1-generation offspring from different litters were mated to produce F2 offspring, and similarly, F2-generation animals produced F3-generation offspring. One group of F3 male offspring was administered either testosterone plus estradiol-17β (T + E2) or sham via capsule implants from postnatal days 70 to 210. Another group was naturally aged to 18 months. Combination diets of HFB + BPA in F0 dams, but not single exposure to either, disrupted spermatogenesis in F3-generation adult males in both the T + E2-implanted group and the naturally aged group. CYP19A1 localization to the acrosome and estrogen receptor beta (ERbeta) localization to the nucleus were associated with impaired spermatogenesis. Finally, expression of methyl-CpG-binding domain-3 (MBD3) was consistently decreased in the HFB and HFB + BPA exposed F1 and F3 testes, suggesting an epigenetic component to this inheritance. However, the severe atrophy within testes present in F1 males was absent in F3 males. In conclusion, the HFB + BPA group demonstrated transgenerational inheritance of the impaired spermatogenesis phenotype, but severity was reduced in the F3 generation.
Keywords	acrosome ; adulthood ; adults ; atrophy ; bisphenol A ; body weight ; endocrine-disrupting chemicals ; epigenetics ; estrogen receptors ; high fat diet ; males ; milk fat ; penetrance ; phenotype ; pregnancy ; progeny ; spermatogenesis ; testosterone
Language	English
Dates of publication	2021-1017
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13103636
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Three-Generation Study of Male Rats Gestationally Exposed to High Butterfat and Bisphenol A: Impaired Spermatogenesis, Penetrance with Reduced Severity.

Ho, Shuk-Mei / Rao, Rahul / Ouyang, Bin / Tam, Neville N C / Schoch, Emma / Song, Dan / Ying, Jun / Leung, Yuet-Kin / Govindarajah, Vinothini / Tarapore, Pheruza

Nutrients

2021 Volume 13, Issue 10

Abstract	Gestational high butterfat (HFB) and/or endocrine disruptor exposure was previously found to disrupt spermatogenesis in adulthood. This study addresses the data gap in our knowledge regarding transgenerational transmission of the disruptive interaction between a high-fat diet and endocrine disruptor bisphenol A (BPA). F0 generation Sprague-Dawley rats were fed diets containing butterfat (10 kcal%) and high in butterfat (39 kcal%, HFB) with or without BPA (25 µg/kg body weight/day) during mating and pregnancy. Gestationally exposed F1-generation offspring from different litters were mated to produce F2 offspring, and similarly, F2-generation animals produced F3-generation offspring. One group of F3 male offspring was administered either testosterone plus estradiol-17β (T + E2) or sham via capsule implants from postnatal days 70 to 210. Another group was naturally aged to 18 months. Combination diets of HFB + BPA in F0 dams, but not single exposure to either, disrupted spermatogenesis in F3-generation adult males in both the T + E2-implanted group and the naturally aged group. CYP19A1 localization to the acrosome and estrogen receptor beta (ERbeta) localization to the nucleus were associated with impaired spermatogenesis. Finally, expression of methyl-CpG-binding domain-3 (MBD3) was consistently decreased in the HFB and HFB + BPA exposed F1 and F3 testes, suggesting an epigenetic component to this inheritance. However, the severe atrophy within testes present in F1 males was absent in F3 males. In conclusion, the HFB + BPA group demonstrated transgenerational inheritance of the impaired spermatogenesis phenotype, but severity was reduced in the F3 generation.
MeSH term(s)	Animals ; Benzhydryl Compounds/toxicity ; Butter ; Diet, High-Fat/adverse effects ; Dietary Fats/adverse effects ; Disease Models, Animal ; Endocrine Disruptors/toxicity ; Epigenesis, Genetic ; Estradiol ; Female ; Infertility, Male/chemically induced ; Infertility, Male/genetics ; Inheritance Patterns ; Male ; Maternal Exposure/adverse effects ; Maternal Nutritional Physiological Phenomena ; Phenols/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/genetics ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis/drug effects ; Spermatogenesis/genetics ; Testis/metabolism
Chemical Substances	Benzhydryl Compounds ; Dietary Fats ; Endocrine Disruptors ; Phenols ; Estradiol (4TI98Z838E) ; Butter (8029-34-3) ; bisphenol A (MLT3645I99)
Language	English
Publishing date	2021-10-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13103636
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer.

Ho, Shuk-Mei / Rao, Rahul / To, Sarah / Schoch, Emma / Tarapore, Pheruza

Endocrine-related cancer

2017 Volume 24, Issue 2, Page(s) 83–96

Abstract: Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased ... ...

Abstract	Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased prostate cancer (PCa) risk in human and animal models. Here, we examine whether exposure of PCa cells (LNCaP, C4-2) to low-dose BPA and its structural analogues (BPS, BPF, BPAF, TBBPA, DMBPA and TMBPA) affects centrosome amplification (CA), a hallmark of cancer initiation and progression. We found that exposure to BPA, BPS, DMBPA and TBBPA, in descending order, increased the number of cells with CA, in a non-monotonic dose-response manner. Furthermore, cells treated with BPA and their analogues initiated centrosome duplication at 8 h after release from serum starvation, significantly earlier in G-1 phase than control cells. This response was attended by earlier release of nucleophosmin from unduplicated centrosomes. BPA-exposed cells exhibited increased expression of cyclin-dependent kinase CDK6 and decreased expression of CDK inhibitors (p21
Language	English
Publishing date	2017-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-16-0175
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4192: Show issues

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Article: Ca

Smithrud, David B / Powers, Lucas / Lunn, Jennifer / Abernathy, Scott / Peschka, Michael / Ho, Shuk-Mei / Tarapore, Pheruza

ACS medicinal chemistry letters

2017 Volume 8, Issue 2, Page(s) 163–167

Abstract: New therapies are needed to eradicate androgen resistant, prostate cancer. Prostate cancer usually metastasizes to bone where the concentration of calcium is high, making ... ...

Abstract	New therapies are needed to eradicate androgen resistant, prostate cancer. Prostate cancer usually metastasizes to bone where the concentration of calcium is high, making Ca
Language	English
Publishing date	2017-01-04
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/acsmedchemlett.6b00347
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Analysis of centrosome localization of BRCA1 and its activity in suppressing centrosomal aster formation.

Tarapore, Pheruza / Hanashiro, Kazuhiko / Fukasawa, Kenji

Cell cycle (Georgetown, Tex.)

2012 Volume 11, Issue 15, Page(s) 2931–2946

Abstract: BRCA1, a product of a familial breast and ovarian cancer susceptibility gene, localizes to centrosomes and physically interacts with γ-tubulin, a key centrosomal protein for microtubule nucleation and anchoring at centrosomes. Here, we performed a ... ...

Abstract	BRCA1, a product of a familial breast and ovarian cancer susceptibility gene, localizes to centrosomes and physically interacts with γ-tubulin, a key centrosomal protein for microtubule nucleation and anchoring at centrosomes. Here, we performed a rigorous analysis of centrosome localization of BRCA1, and found that BRCA1 is specifically associated with mother centrioles in unduplicated centrosomes, and daughter centrioles acquire BRCA1 prior to initiation of duplication, and thus duplicated centrosomes are both bound by BRCA1. We further found that BRCA1 suppresses centrosomal aster formation. In addition, we identified a new domain of BRCA1 critical for γ-tubulin binding, which confers not only its localization to centrosomes, but also its activity to suppress centrosomal aster formation.
MeSH term(s)	BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Centrioles/metabolism ; Centrosome/metabolism ; Female ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; MCF-7 Cells ; RNA Interference ; RNA, Small Interfering ; Spindle Apparatus/metabolism ; Tubulin/metabolism
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; RNA, Small Interfering ; Tubulin ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2012-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.21396
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5881: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors.

Zhou, Zilan / Kennell, Carly / Lee, Joo-Youp / Leung, Yuet-Kin / Tarapore, Pheruza

Nanomedicine : nanotechnology, biology, and medicine

2016 Volume 13, Issue 2, Page(s) 403–410

Abstract: In this study, a development of a novel calcium phosphate-polymer hybrid nanoparticle system is reported.The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties (i.e., ... ...

Abstract	In this study, a development of a novel calcium phosphate-polymer hybrid nanoparticle system is reported.The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties (i.e., inhibitors for microRNA-221 and microRNA-222 (miRi-221/222) and paclitaxel (pac)).miRi-221/222 are hydrophilic and were encapsulated with calcium phosphate by co-precipitation in a water-in-oil emulsion.The precipitates were then coated with an anionic lipid, dioleoylphosphatidic acid (DOPA), to co-encapsulate hydrophobic paclitaxel outside the hydrophilic precipitates and inside the same nanoparticle.The nanoparticles formed by following this approach had a size of about ≤100nm and contained both lipid-coated calcium phosphate/miRi and paclitaxel.This nanoparticle system was found to simultaneously deliver paclitaxel and miRi-221/222 to their intracellular targets, leading to inhibit proliferative mechanisms of miR-221/222 and thus significantly enhancing the therapeutic efficacy of paclitaxel.
MeSH term(s)	Antineoplastic Agents, Phytogenic/administration & dosage ; Calcium Phosphates ; Cell Line, Tumor ; Humans ; MicroRNAs/antagonists & inhibitors ; Nanoparticles ; Paclitaxel/administration & dosage ; Polymers ; Triple Negative Breast Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents, Phytogenic ; Calcium Phosphates ; MIRN221 microRNA, human ; MIRN222 microRNA, human ; MicroRNAs ; Polymers ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2016-08-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2016.07.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Crown Ether Host-Rotaxanes as Cytotoxic Agents.

Smithrud, David B / Wang, Xiaoyang / Tarapore, Pheruza / Ho, Shuk-Mei

ACS medicinal chemistry letters

2012 Volume 4, Issue 1, Page(s) 27–31

Abstract: Highly toxic bacterial ionophores are commonly used in veterinary medicine, but their therapeutic index is too narrow for human usage. With the goal of developing ionophores with a broader therapeutic index, we constructed highly derivatized synthetic ... ...

Abstract	Highly toxic bacterial ionophores are commonly used in veterinary medicine, but their therapeutic index is too narrow for human usage. With the goal of developing ionophores with a broader therapeutic index, we constructed highly derivatized synthetic ionophores. The toxicities of crown ether host-rotaxanes (CEHR's) against the SKOV-3 cell line were measured. The effect of Mg
Language	English
Publishing date	2012-11-08
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/ml3003204
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