scholarly journals Evidence that Cocaine- and Amphetamine-Regulated Transcript Is a Novel Intraovarian Regulator of Follicular Atresia

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5373-5383 ◽  
Author(s):  
Yasuhiro Kobayashi ◽  
Fermin Jimenez-Krassel ◽  
Qinglei Li ◽  
Jianbo Yao ◽  
Ruiping Huang ◽  
...  

Abstract We recently obtained evidence that cocaine- and amphetamine-regulated transcript (CART), a potent anorectic neuropeptide, is expressed in the bovine ovary. The objectives of this study were to characterize bovine ovarian CART and determine its localization, regulation, and regulatory role during follicular development. CART mRNA was detected in stroma of adult ovaries and in large follicles, but was undetectable in several peripheral tissues, fetal ovaries, and corpora lutea. Within the ovary, CART mRNA and peptide were localized to the granulosal layer of some, but not all, antral follicles, with low, but detectable, expression in oocytes and cumulus cells. CART mRNA was undetectable in granulosal cells of dominant ovulatory follicles collected before and after the preovulatory gonadotropin surge, but was detected in the granulosal layer of adjacent subordinate follicles. In addition, amounts of CART mRNA and follicular fluid concentrations of CART peptide were greater in subordinate follicles vs. dominant follicles of the first follicular wave. Furthermore, CART treatment inhibited basal estradiol production, but not progesterone production, by granulosal cells in a dose-dependent fashion, and the effect was dependent on stage of cell differentiation. We conclude that granulosal cell CART expression is temporally regulated and potentially associated with follicle health status, and CART can inhibit granulosal cell estradiol production. Thus, CART may be a novel local regulator of follicular atresia in the bovine ovary.

2016 ◽  
Vol 28 (2) ◽  
pp. 197
Author(s):  
R. Carrasco ◽  
J. Singh ◽  
G. P. Adams

Classical studies established that the removal of one of the paired organs produces a compensatory effect on the remaining organ. In the bovine ovary this aspect has not been examined in detail. We took advantage of follicular and luteal profiles from a previous study to retrospectively examine the effects of ovariectomy before and after ovulation on follicular dynamics of the remaining ovary in cattle. To characterise the prevalence and distribution of tyrosine kinase receptor A in the bovine ovary, the original design involved unilateral ovariectomy of cows at different stages of the periovulatory period. For the purposes of the present study, we combined data into 2 groups, a preovulatory group (n = 6 cows) and a post-ovulatory group (n = 5 cows), to provide sufficient data for statistical interpretation. The cows were examined daily by transrectal ultrasonography to determine the ovarian status. For the preovulatory group, a luteolytic dose of prostaglandin was administered when the dominant follicle of the second follicular wave reached ≥10 mm, and the ovary containing the dominant follicle was removed within 48 h. For the post-ovulatory group, ovariectomy was performed on the ovary containing the newly formed corpus luteum between Days 2 to 6 (Day 0 = ovulation). Unilateral ovariectomy was performed by colpotomy under caudal epidural anaesthesia using a chain ecraseur. After ovariectomy, cows were examined daily by ultrasonography from ovariectomy to the completion of an interovulatory interval (period between 2 ovulations). Single-point data were compared between groups by t-test, and binomial data were compared between groups by Fisher’s exact test. Double ovulations were detected in 3/6 ovariectomized in the preovulatory period and 2/5 ovariectomized in the post-ovulatory period. The first ovulation after ovariectomy tended to occur earlier in the preovulatory group than in the post-ovulatory group (P = 0.08), which was attributed primarily to the development of oversized persistent dominant follicles (~20 mm in diameter for ≥7 days in absence of a corpora lutea) in 2 of 5 cows in the post-ovulatory ovariectomy group. The interovulatory interval after ovariectomy was shorter in the post-ovulatory group than in the preovulatory group (14.6 ± 0.3 v. 20.3 ± 0.6 days; P = 0.01). No distinct patterns were detected in follicular and luteal dynamics between the pre- and post-ovulatory ovariectomy groups. The number of follicles ≥3 mm detected by ultrasonography was greater in the post-ovulatory ovariectomy group than in the preovulatory group on Days 6, 7, 8, and 16 of the first interovulatory interval after ovariectomy. In conclusion, results of this retrospective study support the concept that follicular and luteal effects of removal of one ovary are influenced by the timing of ovariectomy relative to ovulation. A prospective study involving a comparison of ovarian dynamics of the same cows before and after unilateral ovariectomy will provide a better understanding of the disruption that take place and the mechanisms controlling it. Research was supported by the Natural Sciences and Engineering Research Council of Canada.


2013 ◽  
Vol 25 (1) ◽  
pp. 243
Author(s):  
S. Furukawa ◽  
K. Naito ◽  
K. Sugiura

Recent studies have shown the critical roles of fibroblast growth factors (FGFs), including FGF8 produced by oocytes, in regulating follicular development. However, the expression and regulation of the FGF gene family, which consists of 22 ligands and 4 receptors, in the mouse ovary have not been well understood. The aim of the present study was to assess the expression and regulation of FGF ligands and receptors in the mouse ovary. Transcript levels of FGF ligands and receptors in immature (3-week-old) and adult (7- to 8-week-old) ovaries as well as other tissues of B6/DBA2F1 mice were analysed with RT-PCR. Furthermore, expression levels of FGF receptors in cumulus cells (CC) and mural granulosa cells (MG) before and after equine chorionic gonadotropin (eCG) treatment were determined with RT-quantitative PCR. Among 21 FGF ligands examined, 12 and 9 transcripts were detectable in immature and adult ovaries, respectively. More FGF ligands were detected in ovary, testis, heart, and brain compared to other tissues, including liver and spleen. Transcripts of all 4 FGF receptors (Fgfr1–4) were detectable in both immature and adult ovaries. Expression levels of Fgfr1 and Fgfr2 were significantly higher in MG compared with CC before and after the eCG treatment. Levels of Fgfr4 were comparable between MG and CC before the eCG treatment, but became significantly different with higher expression levels in MG after the eCG treatment. Fgfr3 transcripts were barely detectable in CC and MG. Overall levels of Fgfr1 in granulosa cells (CC and MG) were downregulated by eCG treatment, whereas those of Fgfr2 and Fgfr4 were upregulated. In summary, many FGF ligands are expressed, at least in mRNA levels, in mouse ovaries. Moreover, the expression levels of Fgfr transcripts in granulosa cells are dynamically regulated during follicular development.


1978 ◽  
Vol 78 (1) ◽  
pp. 58-75 ◽  
Author(s):  
N B Gilula ◽  
M L Epstein ◽  
W H Beers

Cell-to-cell communication was characterized in cumulus-oocyte complexes from rat ovarian follicles before and after ovulation. Numerous, small gap junctional contacts were present between cumulus cells and oocytes before ovulation. The gap junction are formed on the oocyte surface by cumulus cell processes that transverse the zona pellucida and contact the oolemma. The entire cumulus mass was also connected by gap junctions via cumulus-cumulus interactions. In the hours preceding ovulation, the frequency of gap junctional contacts between cumulus cells and the oocyte was reduced, and the cumulus was disorganized. Electrophysiological measurements indicated that bidirectional ionic coupling was present between the cumulus and oocyte before ovulation. In addition, iontophoretically injected fluorescein dye was tranferred between the oocyte and cumulus cells. Examination of the extent of ionic coupling in cumulus-oocyte specimens before and after ovulation revealed that ionic coupling between the cumulus and oocyte progressively decreased as the time of ovulation approached. In postovulatory specimens, no coupling was detected. Although some proteolytic mechanism may be involved in the disintegration of the cumulus-oocyte complex, neither the cumulus cells nor the oocyte produced detectable levels of plasminogen activator, a protease which is synthesized by membrana granulosa cells. In summary, cell communication is a characterisitc feature of the cumulus-oocyte complex, and this communication is terminated near the time of ovulation. This temporal pattern of the termination of communication between the cumulus and the oocyte may indicate that communication provides a mechanism for regulating the maturation of the oocyte during follicular development before ovulation.


2018 ◽  
Vol 30 (1) ◽  
pp. 192
Author(s):  
R. Carrasco ◽  
C. E. Leonardi ◽  
J. Singh ◽  
G. P. Adams

Neurotrophins are molecules involved in the development and survival of neurons and its cellular projections. Results of recent studies have implicated the local role of the high affinity neurotropin receptor, trkA, in bovine ovarian follicle selection and early luteogenesis (Carrasco et al. 2016 Reprod. Biol. Endocrinol. 14, 47), but innervation and neuropeptide control remains an unexplored aspect of ovarian function. P75 is the low-affinity receptor for all neurotrophins and is expressed in ovarian tissue. The objective of this study was to explore the distribution of P75 neurons and fibres within the ovary and to examine the relationship of these components with follicular development. The ovaries of cows (n = 5) were collected at the time of slaughter, 36 h after induced luteolysis (i.e. proestrus). The ovaries were fixed in 4% paraformaldehyde for 48 h, and samples from the ovarian hilus, medulla, and cortex (3 blocks per ovary) were cryo-sectioned (20–50 µm). Tissue sections were incubated for 48 h with a rabbit antibody against rat P75 or a mouse monoclonal antibody against neurofilament. Immunodetection was visualised by an amplification procedure with horseradish peroxidase using nickel DAB as a chromogen. Sections were counterstained with nuclear fast red for follicle identification. Immunoreactive cell bodies were counted in 10 to 20 fields (40×) per section, and data were expressed based on ovarian areas (cortex, medulla, or hilus) as an average count per 40× field per animal. Data among ovarian regions were compared by ANOVA; differences were considered significant when P < 0.05. Antral follicles ≤5 mm displayed strong immunoreactivity in the theca layer, without reaction in the granulosa cells. In contrast, preovulatory follicles were devoid of P75 immuno-reactivity in the theca layer. Oval P75 immunoreactive neuron-like cells were present in all ovarian areas studied. The neuronal nature of the P75 immunoreactive cells was confirmed by the presence of a similar pattern when adjacent sections were stained for neurofilaments, a protein characteristic of neurons. In the stroma of the ovarian cortex and medulla, neurons were present individually (scattered) rather than grouped; however, a dense network of neurons and fibres was detected immediately beneath the ovarian surface epithelium. No differences between the cortex, medulla, and hilus were found in the mean number of immunoreactive cells (10.6 ± 2.8, 14.4 ± 3.6 and 13.9 ± 2.0 cells/40× field, respectively). Immunoreactive neuron-like cells and fibres were in close proximity to blood vessels in the ovarian medulla. Corpora lutea were devoid of P75 immunoreactivity. In conclusion, results document the existence of a neuronal network in the bovine ovary, displaying an association with follicles at different stages of development. The abundance of neuronal components (i.e. neuron cell bodies and axons) in the ovarian stromal and surface epithelium implies a role of innervation (either extrinsic or intrinsic) in the control of ovarian follicular development and function. Research was supported by the Natural Sciences and Engineering Research Council of Canada.


1968 ◽  
Vol 59 (2_Suppl) ◽  
pp. S7-S33 ◽  
Author(s):  
B. L. Lobel ◽  
E. Levy

ABSTRACT Activities of several hydrolytic enzymes (acid and alkaline phosphatases, ATP-ase and β-glucuronidase) as well as several dehydrogenases (succinic dehydrogenase, NADP and NADPH2 diaphorases, Δ5-3β-, 17β- and 20β-hydroxysteroid dehydrogenases) were studied during the growth and maturation of follicles from primordial to pre-ovulatory in the bovine ovary. Follicular growth apparently commenced with enlargement of the oocyte, and enzymic activities (alkaline phosphatase, ATP-ase, β-glucuronidase and the diaphorases) of this stage were strong in the granulosa; vesicular follicles exhibited strong enzymic activities mainly in the theca. Steroid dehydrogenases were demonstrable in both theca and granulosa of vesicular follicles only. Luteinization of pre-ovulatory follicles, as judged by cytochemical and morphological characteristics, began prior to rupture. A correlation was observed between cytochemically demonstrable enzymic activities and secretory function.


1968 ◽  
Vol 59 (2_Suppl) ◽  
pp. S53-S63 ◽  
Author(s):  
B. L. Lobel ◽  
E. Levy

ABSTRACT Cytochemical changes in activities of hydrolytic enzymes and of dehydrogenases were studied during follicular atresia. Different patterns of enzymic activities were encountered in the different types of atretic follicles. When large vesicular follicles became atretic at the end of the cycle, they underwent a transient luteinization. On the basis of their cytochemical properties, it is suggested that such follicles may be one source of steroidal hormones in the bovine ovary, especially towards the end of the cycle. The bovine ovary apparently does not contain "interstitial tissue" capable of steroidogenesis.


1977 ◽  
Vol 86 (2) ◽  
pp. 380-383 ◽  
Author(s):  
G. H. Zeilmaker ◽  
C. M. P. M. Verhamme

ABSTRACT Lactate concentrations were determined in pre-ovulatory follicles of rats at pro-oestrus before and after onset of oocyte maturation. It appeared that high concentrations prevail before and after the time of the expected LH surge (27 mM). The level in serum was about 5 mm. Explanted oocytes obtained from pre-puberal rats and surrounded by cumulus cells, matured in the presence of 20 mm. lactate as sole exogenous energy source. It is argued that oxygen may be the limiting factor suppressing oocyte maturation in vivo.


1991 ◽  
Vol 124 (4) ◽  
pp. 357-363 ◽  
Author(s):  
Antonio R. Martinez ◽  
Rob E. Bernardus ◽  
Danka Kucharska ◽  
Joop Schoemaker

Abstract. A urinary luteinizing hormone test was utilized to predict ovulation in 99 spontaneous, 122 clomiphene citrate, and 82 human menopausal gonadotropin stimulated cycles. Tests were performed in early morning and evening specimens and follicular development was monitored by daily ultrasonography. A positive detection rate of 98, 97, and 94%, respectively, was obtained. Evidence of luteinized unruptured follicles was seen more frequently in stimulated cycles, concurring with negative test results. In 2 spontaneous, 1 clomiphene citrate and 5 hMG induced cycles two distinct LH surges were detected concomitant with a pattern of follicular atresia and subsequent new follicular development. Most ovulations occurred between 16 and 28 h after LH detection, signficantly earlier in spontaneous than in clomiphene citrate stimulated cycles (p<0.02), whereas pre-ovulatory follicles were larger in the clomiphene citrate group (p<0.001). The mean duration of the follicular and luteal phases, as calculated from the LH peak, was substantially shorter in the hMG cycles than in the other two groups (p<0.001).


2019 ◽  
Vol 9 (o3) ◽  
Author(s):  
Suaad Muhssen Ghazi ◽  
Fatin Shallal Farhan

Vitamin D deficiency is common in women with polycystic ovarian syndrome. Vitamin D plays an important physiologic role in reproductive functions of ovarian follicular development and luteinization through altering anti-müllerian hormone signaling, follicular stimulating hormone activity and progesterone production in human granulose cells. Vitamin D is precipitated in adipose fat tissues, making it notable to be used for the body as a result; obese people with high body mass index are already highly expected to have low levels of serum vitamin D.


Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Noriyuki Takahashi ◽  
Wataru Tarumi ◽  
Bunpei Ishizuka

Most of the previous studies on ovarian hyaluronan (HA) have focused on mature antral follicles or corpora lutea, but scarcely on small preantral follicles. Moreover, the origin of follicular HA is unknown. To clarify the localization of HA and its synthases in small growing follicles, involvement of HA in follicle growth, and gonadotropin regulation of HA synthase (Has) gene expression, in this study, perinatal, immature, and adult ovaries of Wistar-Imamichi rats were examined histologically and biochemically and byin vitrofollicle culture. HA was detected in the extracellular matrix of granulosa and theca cell layers of primary follicles and more advanced follicles. Ovarian HA accumulation ontogenetically started in the sex cords of perinatal rats, and its primary site shifted to the intrafollicular region of primary follicles within 5 days of birth. TheHas1–3mRNAs were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels ofHas1andHas2genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins in immature acyclic rats. TheHas1andHas2mRNAs were predominantly localized in the theca and granulosa cell layers of growing follicles respectively. Treatments with chemicals known to reduce ovarian HA synthesis induced follicular atresia. More directly, the addition ofStreptomyceshyaluronidase, which specifically degrades HA, induced the arrest of follicle growth in anin vitroculture system. These results indicate that gonadotropin-regulated HA synthesis is involved in normal follicle growth.


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