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Artikel ; Online: The history, use, and challenges of therapeutic somatic cell and germline gene editing.

Ryu, Junghyun / Adashi, Eli Y / Hennebold, Jon D

2023 Band 120, Heft 3 Pt 1, Seite(n) 528–538

Abstract: The advent of directed gene-editing technologies now over 10 years ago ushered in a new era of precision medicine wherein specific disease-causing mutations can be corrected. In parallel with developing new gene-editing platforms, optimizing their ... ...

Abstract	The advent of directed gene-editing technologies now over 10 years ago ushered in a new era of precision medicine wherein specific disease-causing mutations can be corrected. In parallel with developing new gene-editing platforms, optimizing their efficiency and delivery has been remarkable. With their development, there has been interest in using gene-editing systems for correcting disease mutations in differentiated somatic cells ex vivo or in vivo or for germline gene editing in gametes or 1-cell embryos to potentially limit genetic diseases in the offspring and in future generations. This review details the development and history of the current gene-editing systems and the advantages and challenges in their use for somatic cell and germline gene editing.
Mesh-Begriff(e)	Humans ; Gene Editing ; CRISPR-Cas Systems ; Mutation ; Germ Cells ; Precision Medicine
Sprache	Englisch
Erscheinungsdatum	2023-03-05
Erscheinungsland	United States
Dokumenttyp	Review ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2023.02.040
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Generation of a rhesus macaque induced pluripotent stem cell line (riPSC05) under feeder-free conditions.

Lara, Mary Jasmine D / Wamaitha, Sissy E / Arabpour, Auriana / Hennebold, Jon D / Clark, Amander T / Sosa, Enrique

Stem cell research

2023 Band 73, Seite(n) 103241

Abstract: We generated and characterized a rhesus macaque induced pluripotent stem cell (iPSC) line using induced reprogramming of fibroblasts isolated from a rhesus macaque fetus. The fibroblasts were expanded and then reprogrammed using non-integrating Sendai ... ...

Abstract	We generated and characterized a rhesus macaque induced pluripotent stem cell (iPSC) line using induced reprogramming of fibroblasts isolated from a rhesus macaque fetus. The fibroblasts were expanded and then reprogrammed using non-integrating Sendai virus technology. This line is available as riPSC05. The authenticity of riPSC05 was confirmed through the expression of pluripotent and self-renewal markers, in vitro-directed differentiation towards three germ layers (ectoderm, mesoderm, and endoderm), karyotyping, and STR analysis.
Mesh-Begriff(e)	Animals ; Induced Pluripotent Stem Cells/metabolism ; Cellular Reprogramming ; Macaca mulatta ; Cell Differentiation ; Karyotyping ; Fibroblasts/metabolism
Sprache	Englisch
Erscheinungsdatum	2023-11-04
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2023.103241
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: ABCC4 is a PGE2 efflux transporter in the ovarian follicle: A mediator of ovulation and a potential non-hormonal contraceptive target.

Yerushalmi, Gil M / Shuraki, Batel / Yung, Yuval / Maman, Ettie / Baum, Micha / Hennebold, Jon D / Adashi, Eli Y / Hourvitz, Ariel

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Band 37, Heft 4, Seite(n) e22858

Abstract: The role of prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is ... ...

Abstract	The role of prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is significantly upregulated in preovulatory human granulosa cells (GCs). We found that PGE2 efflux in cultured human GCs is mediated by ABCC4 thus regulating its extracellular concentration. The ABCC4 inhibitor probenecid demonstrated effective blocking of ovulation and affects key ovulatory genes in female mice in vivo. We postulate that the reduction in PGE2 efflux caused by the inhibition of ABCC4 activity in GCs decreases the extracellular concentration of PGE2 and its ovulatory effect. Treatment of female mice with low dose of probenecid as well as with the PTGS inhibitor indomethacin or Meloxicam synergistically blocks ovulation. These results support the hypothesis that ABCC4 has an important role in ovulation and might be a potential target for non-hormonal contraception, especially in combination with PGE2 synthesis inhibitors. These findings may fill the gap in understanding the role of ABCC4 in PGE2 signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment and control of fertility.
Mesh-Begriff(e)	Humans ; Female ; Mice ; Animals ; Dinoprostone/metabolism ; Contraceptive Agents/metabolism ; Contraceptive Agents/pharmacology ; Probenecid/metabolism ; Probenecid/pharmacology ; Ovarian Follicle/metabolism ; Ovulation/physiology ; Membrane Transport Proteins/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/metabolism
Chemische Substanzen	Dinoprostone (K7Q1JQR04M) ; Contraceptive Agents ; Probenecid (PO572Z7917) ; Membrane Transport Proteins ; ATP-Binding Cassette Transporters ; ABCC4 protein, human ; Multidrug Resistance-Associated Proteins
Sprache	Englisch
Erscheinungsdatum	2023-03-20
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202101931RR
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Preventing granulosa cell apoptosis through the action of a single microRNA.

Hennebold, Jon D

Biology of reproduction

2010 Band 83, Heft 2, Seite(n) 165–167

Mesh-Begriff(e)	Animals ; Apoptosis/genetics ; Female ; Gene Expression ; Granulosa Cells/metabolism ; Granulosa Cells/physiology ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; MicroRNAs/physiology ; Ovary/physiology
Chemische Substanzen	MIRN21 microRNA, mouse ; MicroRNAs
Sprache	Englisch
Erscheinungsdatum	2010-06-10
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1095/biolreprod.110.086173
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Coordination of Ovulation and Oocyte Maturation: A Good Egg at the Right Time.

Robker, Rebecca L / Hennebold, Jon D / Russell, Darryl L

Endocrinology

2018 Band 159, Heft 9, Seite(n) 3209–3218

Abstract: Ovulation is the appropriately timed release of a mature, developmentally competent oocyte from the ovary into the oviduct, where fertilization occurs. Importantly, ovulation is tightly linked with oocyte maturation, demonstrating the interdependency of ... ...

Abstract	Ovulation is the appropriately timed release of a mature, developmentally competent oocyte from the ovary into the oviduct, where fertilization occurs. Importantly, ovulation is tightly linked with oocyte maturation, demonstrating the interdependency of these two parallel processes, both essential for female fertility. Initiated by pituitary gonadotropins, the ovulatory process is mediated by intrafollicular paracrine factors from the theca, mural, and cumulus granulosa cells, as well as the oocyte itself. The result is the induction of cumulus expansion, proteolysis, angiogenesis, inflammation, and smooth muscle contraction, which are each required for follicular rupture. These complex intercellular communication networks and the essential ovulatory genes have been well defined in mouse models and are highly conserved in primates, including humans. Importantly, recent discoveries in regulation of ovulation highlight new areas of investigation.
Mesh-Begriff(e)	Animals ; Cumulus Cells/physiology ; Female ; Follicle Stimulating Hormone/metabolism ; Follicle Stimulating Hormone/physiology ; Humans ; Luteinizing Hormone/metabolism ; Luteinizing Hormone/physiology ; Mice ; Muscle Contraction/physiology ; Muscle, Smooth ; Neovascularization, Physiologic/physiology ; Oocytes/growth & development ; Oocytes/metabolism ; Ovarian Follicle/physiology ; Ovulation/metabolism ; Ovulation/physiology ; Primates ; Proteolysis ; Theca Cells/physiology ; Time Factors
Chemische Substanzen	Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0)
Sprache	Englisch
Erscheinungsdatum	2018-07-16
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2018-00485
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Long-term Hyperandrogenemia and/or Western-style Diet in Rhesus Macaque Females Impairs Preimplantation Embryogenesis.

Ravisankar, Sweta / Murphy, Melinda J / Redmayne-Titley, Nash / Davis, Brett / Luo, Fangzhou / Takahashi, Diana / Hennebold, Jon D / Chavez, Shawn L

Endocrinology

2022 Band 163, Heft 4

Abstract: Hyperandrogenemia and obesity are common in women with polycystic ovary syndrome, but it is currently unclear how each alone or in combination contribute to reproductive dysfunction and female infertility. To distinguish the individual and combined ... ...

Abstract	Hyperandrogenemia and obesity are common in women with polycystic ovary syndrome, but it is currently unclear how each alone or in combination contribute to reproductive dysfunction and female infertility. To distinguish the individual and combined effects of hyperandrogenemia and an obesogenic diet on ovarian function, prepubertal female rhesus macaques received a standard control (C) diet, testosterone (T) implants, an obesogenic Western-style diet (WSD), or both (T + WSD). After 5 to 6 years of treatment, the females underwent metabolic assessments and controlled ovarian stimulations. Follicular fluid (FF) was collected for steroid and cytokine analysis and the oocytes fertilized in vitro. Although the T + WSD females exhibited higher insulin resistance compared to the controls, there were no significant differences in metabolic parameters between treatments. Significantly higher concentrations of CXCL-10 were detected in the FF from the T group, but no significant differences in intrafollicular steroid levels were observed. Immunostaining of cleavage-stage embryos revealed multiple nuclear abnormalities in the T, WSD, and T + WSD groups. Single-cell DNA sequencing showed that while C embryos contained primarily euploid blastomeres, most cells in the other treatment groups were aneuploid. Despite yielding a higher number of mature oocytes, T + WSD treatment resulted in significantly reduced blastocyst formation rates compared to the T group. RNA sequencing analysis of individual blastocysts showed differential expression of genes involved in critical implantation processes between the C group and other treatments. Collectively, we show that long-term WSD consumption reduces the capacity of fertilized oocytes to develop into blastocysts and that the addition of T further impacts gene expression and embryogenesis.
Mesh-Begriff(e)	Animals ; Blastocyst ; Diet, Western/adverse effects ; Embryonic Development ; Female ; Humans ; Hyperandrogenism/complications ; Macaca mulatta
Sprache	Englisch
Erscheinungsdatum	2022-02-22
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqac019
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Rapid, accurate mapping of transgene integration in viable rhesus macaque embryos using enhanced-specificity tagmentation-assisted PCR.

Ryu, Junghyun / Chan, William / Wettengel, Jochen M / Hanna, Carol B / Burwitz, Benjamin J / Hennebold, Jon D / Bimber, Benjamin N

Molecular therapy. Methods & clinical development

2022 Band 24, Seite(n) 241–254

Abstract: Genome engineering is a powerful tool ... ...

Abstract	Genome engineering is a powerful tool for
Sprache	Englisch
Erscheinungsdatum	2022-01-19
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2022.01.009
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial.

Edelman, Alison B / Hennebold, Jon D / Bond, Kise / Lim, Jeong Y / Cherala, Ganesh / Archer, David F / Jensen, Jeffrey T

Obstetrics and gynecology

2022 Band 140, Heft 1, Seite(n) 48–54

Abstract: Objective: To assess whether dose escalation (ie, doubling the dose) of emergency contraception that contains levonorgestrel (LNG) improves pharmacodynamic outcomes in individuals with obesity.: Methods: We enrolled healthy, reproductive-age ... ...

Abstract	Objective: To assess whether dose escalation (ie, doubling the dose) of emergency contraception that contains levonorgestrel (LNG) improves pharmacodynamic outcomes in individuals with obesity. Methods: We enrolled healthy, reproductive-age individuals with regular menstrual cycles, body mass index (BMI) higher than 30, and weight at least 176 lbs in a randomized pharmacodynamic study. After confirming ovulation (luteal progesterone level greater than 3 ng/mL), we monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle measuring 15 mm or greater was visualized. At that point, participants received either oral emergency contraception with LNG 1.5 mg or 3 mg (double dose) and returned for daily monitoring for up to 7 days. Our primary outcome was the difference in the proportion of participants with no follicle rupture 5 days postdosing (yes or no) between groups. The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease). Results: A total of 70 enrolled and completed study procedures. The two groups had similar baseline demographics (mean age 28 years, BMI 38). We found no difference between groups in the proportion of participants without follicle rupture more than 5 days post-LNG dosing (LNG 1.5 mg: 18/35 [51.4%]; LNG 3.0 mg: 24/35 [68.6%], P=.14). Among participants with follicle rupture before 5 days, the time to rupture did not differ between groups (day at 75% probability of no rupture is day 2 for both groups). Conclusion: Individuals with higher BMIs and weights experience a higher risk of failure of emergency contraception with LNG and exhibit an altered pharmacokinetic profile. However, the simple strategy of doubling the dose does not appear to be an effective intervention to improve outcomes. Clinical trial registration: ClinicalTrials.gov, 02859337.
Mesh-Begriff(e)	Adult ; Contraception, Postcoital ; Female ; Humans ; Levonorgestrel ; Obesity/drug therapy ; Ovulation ; Progesterone
Chemische Substanzen	Progesterone (4G7DS2Q64Y) ; Levonorgestrel (5W7SIA7YZW)
Sprache	Englisch
Erscheinungsdatum	2022-06-07
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/AOG.0000000000004717
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Transcriptome analysis during photostimulated recrudescence reveals distinct patterns of gene regulation in Siberian hamster ovaries†.

Leon, Kathleen / Hennebold, Jon D / Fei, Suzanne S / Young, Kelly A

Biology of reproduction

2019 Band 102, Heft 3, Seite(n) 539–559

Abstract: In Siberian hamsters, exposure to short days (SDs, 8 h light:16 h dark) reduces reproductive function centrally by decreasing gonadotropin secretion, whereas subsequent transfer of photoinhibited hamsters to stimulatory long days (LDs, 16 L:8 D) promotes ...

Abstract	In Siberian hamsters, exposure to short days (SDs, 8 h light:16 h dark) reduces reproductive function centrally by decreasing gonadotropin secretion, whereas subsequent transfer of photoinhibited hamsters to stimulatory long days (LDs, 16 L:8 D) promotes follicle stimulating hormone (FSH) release inducing ovarian recrudescence. Although differences between SD and LD ovaries have been investigated, a systematic investigation of the ovarian transcriptome across photoperiod groups to identify potentially novel factors that contribute to photostimulated restoration of ovarian function had not been conducted. Hamsters were assigned to one of four photoperiod groups: LD to maintain ovarian cyclicity, SD to induce ovarian regression, or post transfer (PT), where females housed in SD for 14-weeks were transferred to LD for 2-days or 1-week to reflect photostimulated ovaries prior to (PTd2) and following (PTw1) the return of systemic FSH. Ovarian RNA was extracted to create RNA-sequencing libraries and short-read sequencing Illumina assays that mapped and quantified the ovarian transcriptomes (n = 4/group). Ovarian and uterine masses, plasma FSH, and numbers of antral follicles and corpora lutea decreased in SD as compared to LD ovaries (P < 0.05). When reads were aligned to the mouse genome, 18 548 genes were sufficiently quantified. Most of the differentially expressed genes noted between functional LD ovaries and regressed SD ovaries; however, five main expression patterns were identified across photoperiod groups. These results, generally corroborated by select protein immunostaining, provide a map of photoregulated ovary function and identify novel genes that may contribute to the photostimulated resumption of ovarian activity.
Mesh-Begriff(e)	Animals ; Estrous Cycle/genetics ; Estrous Cycle/metabolism ; Female ; Follicle Stimulating Hormone/blood ; Gene Expression Profiling ; Gene Expression Regulation ; Ovarian Follicle/metabolism ; Ovary/metabolism ; Phodopus ; Photoperiod
Chemische Substanzen	Follicle Stimulating Hormone (9002-68-0)
Sprache	Englisch
Erscheinungsdatum	2019-11-13
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1093/biolre/ioz210
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Ovarian germline stem cells: an unlimited source of oocytes?

Hanna, Carol B / Hennebold, Jon D

Fertility and sterility

2014 Band 101, Heft 1, Seite(n) 20–30

Abstract: While there has been progress in directing the development of embryonic stem cells and induced pluripotent stem cells toward a germ cell state, their ability to serve as a source of functional oocytes in a clinically relevant model or situation has yet ... ...

Abstract	While there has been progress in directing the development of embryonic stem cells and induced pluripotent stem cells toward a germ cell state, their ability to serve as a source of functional oocytes in a clinically relevant model or situation has yet to be established. Recent studies suggest that the adult mammalian ovary is not endowed with a finite number of oocytes, but instead possesses stem cells that contribute to their renewal. The ability to isolate and promote the growth and development of such ovarian germline stem cells (GSCs) would provide a novel means to treat infertility in women. Although such ovarian GSCs are well characterized in nonmammalian model organisms, the findings that support the existence of adult ovarian GSCs in mammals have been met with considerable evidence that disputes their existence. This review details the lessons provided by model organisms that successfully utilize ovarian GSCs to allow for a continual and high level of female germ cell production throughout their life, with a specific focus on the cellular mechanisms involved in GSC self-renewal and oocyte development. Such an overview of the role that oogonial stem cells play in maintaining fertility in nonmammalian species serves as a backdrop for the data generated to date that supports or disputes the existence of GSCs in mammals as well as the future of this area of research in terms of its potential for any application in reproductive medicine.
Mesh-Begriff(e)	Adult Stem Cells/physiology ; Animals ; Female ; Germ Cells/physiology ; Humans ; Oocytes/physiology ; Ovary/cytology ; Ovary/physiology
Sprache	Englisch
Erscheinungsdatum	2014-01-02
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2013.11.009
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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