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Reproductive Toxicology (Elmsford, N.Y.) Oct 2021Di(2-ethylhexyl) phthalate (DEHP) is a chemical commonly used as a plasticizer to render polyvinyl chloride products more durable and flexible. Although exposure to DEHP...
Di(2-ethylhexyl) phthalate (DEHP) is a chemical commonly used as a plasticizer to render polyvinyl chloride products more durable and flexible. Although exposure to DEHP has raised many health concerns due to the identification of DEHP as an endocrine disruptor, it is still used in consumer products, including polyvinyl chloride plastics, medical tubing, car interiors, and children's toys. To investigate the impact of early life exposure to DEHP on the ovary and testes, newborn piglets were orally dosed with DEHP (20 or 200 mg/kg/day) or vehicle control (tocopherol-stripped corn oil) for 21 days. Following treatment, ovaries, testes, and sera were harvested for histological assessment and measurement of steroid hormone levels. In male piglets, progesterone and pregnenolone levels were significantly lower in both treatment groups compared to control, whereas in female piglets, progesterone was significantly higher in the 20 mg group compared to control, indicating sex-specific effects in a non-monotonic manner. Follicle numbers and gene expression of steroidogenic enzymes and apoptotic factors were not altered in treated ovaries compared to controls. In DEHP-treated testes, germ cell migration was impaired and germ cell death was significantly increased compared to controls. Overall, the results of this study suggest that neonatal exposure to DEHP in pigs leads to sex-specific disruption of the reproductive system.
Topics: Animals; Animals, Newborn; Diethylhexyl Phthalate; Endocrine Disruptors; Female; Gene Expression; Gonadal Steroid Hormones; Male; Ovary; Sex Characteristics; Swine; Testis
PubMed: 34425191
DOI: 10.1016/j.reprotox.2021.08.004 -
Reproductive Sciences (Thousand Oaks,... Jan 2013Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated... (Review)
Review
Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated in the field of reproductive biology since March 2004, when a mouse study posed the first serious challenge to the dogma of a fixed pool of oocytes being endowed at birth in more than 50 years. Other studies have since been put forth that further question the validity of this dogma, including the isolation of OSCs from neonatal and adult mouse ovaries by 4 independent groups using multiple strategies. Two of these groups also reported that isolated mouse OSCs, once transplanted back into ovaries of adult female mice, differentiate into fully functional eggs that ovulate, fertilize, and produce healthy embryos and offspring. Arguably, one of the most significant advances in this emerging field was provided by a new research study published this year, which reported the successful isolation and functional characterization of OSCs from ovaries of reproductive age women. Two commentaries on this latest work, one cautiously supportive and one highly skeptical, were published soon afterward. This article evaluates the current literature regarding postnatal oogenesis in mammals and discusses important next steps for future work on OSC biology and function.
Topics: Animals; Cell Separation; Female; Flow Cytometry; Forecasting; Humans; Mice; Oogonia; Ovary; Stem Cells
PubMed: 23024060
DOI: 10.1177/1933719112462632 -
Ultrasound in Obstetrics & Gynecology :... Sep 2002To determine ovarian blood flow characteristics using three-dimensional power Doppler ultrasound.
OBJECTIVE
To determine ovarian blood flow characteristics using three-dimensional power Doppler ultrasound.
METHODS
We examined 30 patients (30 cycles) prior to the start of their in vitro fertilization treatment in the late follicular phase using three-dimensional power Doppler ultrasound. The volume, vascularization index, flow index, vascularization flow index, mean grayness and the presence of the dominant follicle were determined for each ovary separately.
RESULTS
The dominant follicle could be detected in 24 out of 30 cycles (80.0%). The volume of the dominant ovary was 9.9 (standard deviation, 4.0) cm3 and the volume of the non-dominant ovary 6.8 (standard deviation, 2.8) cm3 (P < 0.001). Mean grayness in the dominant ovary was 43.3 (standard deviation, 5.0) and in the non-dominant 47.2 (standard deviation, 4.0) (P < 0.001), but no other differences could be observed between dominant and non-dominant ovaries. The shell with a diameter of 2 mm surrounding the dominant follicle had a higher vascularization index (mean, 9.0; standard deviation, 5.9) and vascularization flow index (mean, 4.2; standard deviation, 2.8) than the whole dominant ovary (mean, 5.5; standard deviation, 2.5 and mean, 2.5; standard deviation, 1.3, respectively) (P = 0.003 and 0.002, respectively). In the cycles without a dominant follicle (n = 6), flow index (mean, 50.0; standard deviation, 5.9) and vascularization flow index (mean, 7.3; standard deviation, 6.2) on the left side were higher than on the right side (mean, 40.2; standard deviation, 3.1; mean, 1.5; standard deviation, 1.4; P-values 0.013 and 0.046, respectively).
CONCLUSION
In the dominant ovary, the volume was higher and mean grayness lower than in the non-dominant ovary. The vascularization index in the shell surrounding the dominant follicle was higher than the average vascularization index in the whole dominant ovary. In addition, there were differences in the vascularization and flow indices between right and left ovaries, which may be related to the anatomical difference in the venous drainage between right and left ovaries.
Topics: Female; Fertilization in Vitro; Follicular Phase; Humans; Imaging, Three-Dimensional; Ovary; Ultrasonography
PubMed: 12230453
DOI: 10.1046/j.1469-0705.2002.00777.x -
Cell Transplantation Aug 2018Pigs share many anatomical and physiological features with humans, offering a unique and viable model for biomedical research. Although porcine female germline stem...
Pigs share many anatomical and physiological features with humans, offering a unique and viable model for biomedical research. Although porcine female germline stem cells (FGSCs) were identified in the juvenile ovary, no reports described the isolation and purification of FGSCs from the pig at sexual maturity. Here, we isolated, purified, and cultured FGSCs from porcine ovaries at sexual maturity. Furthermore, we established and characterized the porcine FGSC (pFGSC) lines. In addition, we found that pFGSC lines could differentiate into oocytes when injection into tissue grafts, including human ovarian tissues. The results show that FGSCs exist in ovaries of Banna mini-pigs at juvenile and sexually maturity. These findings have implications in animal biotechnology applications and regeneration medicine.
Topics: Animals; Cell Differentiation; Cell Separation; Cells, Cultured; Female; Oocytes; Oogenesis; Oogonial Stem Cells; Ovary; Sexual Maturation; Swine; Swine, Miniature
PubMed: 29991280
DOI: 10.1177/0963689718784878 -
Biomedicine & Pharmacotherapy =... Dec 2018One of the challenges that must be overcome during ovarian tissue transplantation is Ischaemia/Reperfusion Injury (IRI). The most important hypothesis explaining the...
One of the challenges that must be overcome during ovarian tissue transplantation is Ischaemia/Reperfusion Injury (IRI). The most important hypothesis explaining the cellular events in I/R processes are calcium overload and oxygen free radicals constitute. Here, we study the effect of verapamil on IRI, and consequently on follicle survival during ovarian transplants in an autograft model. Female mice were randomly assigned into three groups in order to ovarian autotransplantation as follow: Group 1 (Control group), Group 2 (Transplanted group) and Groups 3 (Transplanted + Verapamil group). The grafted ovaries were collected at 3, 7 and 14 days after transplantation for evaluation of follicle content and morphology, apoptosis and Malondialdehyde (MDA) concentration. The results showed that verapamil treatment significantly preserved primordial follicular reserve and reduced the number of degenerated follicles compared to the transplanted group (P < 0.05). MDA levels were significantly higher on the 14th day after transplantation, in group 2 than in group 3. In conclusion, verapamil treatment is effective for the preservation of the follicular pool and reducing tissue damage induced by transplantation of ovarian tissue.
Topics: Animals; Apoptosis; Calcium Channel Blockers; Female; Malondialdehyde; Mice; Ovary; Reperfusion Injury; Verapamil
PubMed: 30372833
DOI: 10.1016/j.biopha.2018.09.130 -
Histological and stereological changes in growing and regressing chicken ovaries during development.Anatomical Record (Hoboken, N.J. : 2007) May 2011The aim of this study was to evaluate the sequence of the histological and stereological changes that occur in diverse components of left growing and right regressing...
The aim of this study was to evaluate the sequence of the histological and stereological changes that occur in diverse components of left growing and right regressing ovaries of Gallus domesticus as well as the variations in the number and size of the different cell subpopulations from 8-day-old chicken embryo to 4-week-old chickens. Results indicate a bilateral asymmetry in favor of the left ovary at all ages studied. The left ovary shows cortex and medulla, but the right ovary has no cortex, only a medulla. Stereological results show in the left ovary an increase in total volume of all components of the ovarian medulla with advancing development. The right ovary follows a similar pattern until the age of 1-day-old chicken, to regress afterward, thereby, reducing the total volume of blood vessels, lacunar channels, and interstitium, but increasing the total volume of interstitial cells as development progresses; consequently, the total volume of interstitial cells is the dominant component in the right ovary of 4-week-old chickens. Results also reveal that the increase in total volume of interstitial cells in the left ovary at all ages and in the right ovary from 8-day-old chicken embryo to 1-day-old chicken is due to hyperplasia and cell hypertrophy of interstitial cells; hence, in the right ovary, cell hypertrophy is the main cause for the increase in the total volume of interstitial cells from 1-week-old to 4-week-old chickens.
Topics: Animals; Chick Embryo; Chickens; Female; Ovary
PubMed: 21416628
DOI: 10.1002/ar.21364 -
Genomics Nov 2021The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of...
The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of the female reproductive system. However, it remains unclear which type of ovarian cells are easily infected by SARS-CoV-2 and whether ovarian infectivity differs from puberty to menopause. In this study, public datasets containing bulk and single-cell RNA-Seq data derived from ovarian tissues were analyzed to demonstrate the mRNA expression and protein distribution of the two key entry receptors for SARS-CoV-2-angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2). Furthermore, an immunohistochemical study of ACE2 and TMPRSS2 in human ovaries of different ages was conducted. Differentially expressed gene (DEG) analysis of ovaries of different ages and with varying ovarian reserves was conducted to explore the potential functions of ACE2 and TMPRSS2 in the ovary. The analysis of the public datasets indicated that the co-expression of ACE2 and TMPRSS2 was observed mostly in oocytes and partially in granulosa cells. However, no marked difference was observed in ACE2 or TMPRSS2 expression between young and old ovaries and ovaries with low and high reserves. Correspondingly, ACE2 and TMPRSS2 were detected in the human ovarian cortex and medulla, especially in oocytes of different stages, with no observed variations in their expression level in ovaries of different ages, which was consistent with the results of bioinformatic analyses. Remarkably, DEG analysis showed that a series of viral infection-related pathways were more enriched in ACE2-positive ovarian cells than in ACE2-negative ovarian cells, suggesting that SARS-CoV-2 may potentially target specific ovarian cells and affect ovarian function. However, further fundamental and clinical research is still needed to monitor the process of SARS-CoV-2 entry into ovarian cells and the long-term effects of SARS-CoV-2 infection on the ovarian function in recovered females.
Topics: Adult; Age Factors; Aged; Angiotensin-Converting Enzyme 2; Animals; Female; Gene Expression Regulation; Humans; Macaca fascicularis; Menopause; Middle Aged; Ovary; Puberty; RNA, Messenger; SARS-CoV-2; Serine Endopeptidases; Virus Internalization; Young Adult
PubMed: 34418496
DOI: 10.1016/j.ygeno.2021.08.012 -
Biological & Pharmaceutical Bulletin 2021Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown....
Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 10 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.
Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Cell Proliferation; Dose-Response Relationship, Drug; Female; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Invasiveness; Ovary
PubMed: 33390553
DOI: 10.1248/bpb.b20-00637 -
The Journal of Reproduction and... Feb 2005The present study was conducted to investigate the effects of storage time and temperature of porcine ovaries on the quality and nuclear maturation in vitro of oocytes...
The present study was conducted to investigate the effects of storage time and temperature of porcine ovaries on the quality and nuclear maturation in vitro of oocytes obtained from stored ovaries and their subsequent development after in vitro fertilization. The ovaries were stored in physiological saline for 0, 3, 6, 9 and 12 h at various temperatures (4, 15, 25 and 35 C). The pH of follicular fluid obtained from the ovaries, DNA fragmentation of the oocyte nucleus and meiotic competence of oocytes were examined. Some oocytes from ovaries stored at 15, 25 and 35 C for 6 h were fertilized in vitro, and then cultured for 7 days to examine the ability of embryos to develop to the blastocyst stage. When the ovaries were stored at 35 C, the pH of follicular fluid decreased and the proportions of oocytes with DNA fragmented nuclei increased as the storage time was prolonged, and the storage of ovaries for 6, 9 and 12 h resulted in lower maturation rates of oocytes. When the ovaries were stored at 4, 15, 25 and 35 C for 6 h, the storage at higher temperatures (> or =15 C) decreased the pH of follicular fluid and induced nucleic DNA fragmentation in higher proportions of oocytes. None of the oocytes from ovaries stored at 4 C reached metaphase II. The storage of ovaries at 15 C reduced the rates of in vitro fertilized oocytes and subsequent embryo development, but there were no significant differences in the rates of fertilization and blastocyst formation between oocytes from ovaries stored at 25 C and 35 C. Our findings indicate that the storage of ovaries at 25-35 C for 6 h is effective for maintaining the developmental competence of porcine oocytes even though the development rates were lower than those of ovaries stored at 35 C for 3 h.
Topics: Animals; Blastocyst; Cell Nucleus; Culture Techniques; DNA Damage; DNA Fragmentation; Embryonic Development; Female; Fertilization in Vitro; Hydrogen-Ion Concentration; In Situ Nick-End Labeling; Male; Oocytes; Ovarian Follicle; Ovary; Specimen Handling; Spermatozoa; Swine; Temperature; Time Factors
PubMed: 15750300
DOI: 10.1262/jrd.51.87 -
The Journal of Clinical Investigation Aug 1993Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts...
Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific radioimmunoassay, we measured IrCRH in extracts of rat ovaries (0.042-0.126 pmol/g wet tissue). The mobility of the ovarian IrCRH molecule was similar to that of rat/human CRH by reverse phase HPLC. To investigate the CRH action in the ovary, we identified, characterized, and localized CRH receptors in the rat ovary. Binding was linear with increasing tissue concentration, saturable, and of high affinity. Scatchard analysis of 125I-Tyr-ovine CRH competitive displacement curves indicated a high affinity binding site with a Kd of approximately 6 nM and a Bmax value of approximately 61 fM/mg protein. Autoradiographic studies revealed CRH receptors primarily in ovarian theca and stroma. We conclude that IrCRH and CRH receptors are present in rat ovaries, suggesting that this neuropeptide may play a regulatory role in this gonad, perhaps through its proinflammatory properties and/or by participating in the auto/paracrine regulation of steroid biosynthesis. Functional studies are necessary to define the role(s) of CRH in the ovary.
Topics: Animals; Autoradiography; Binding, Competitive; Chromatography, High Pressure Liquid; Corpus Luteum; Corticotropin-Releasing Hormone; Female; Granulosa Cells; Humans; Immunohistochemistry; Iodine Radioisotopes; Ovarian Follicle; Ovary; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Receptors, Neurotransmitter; Theca Cells
PubMed: 8394389
DOI: 10.1172/JCI116672