scholarly journals Survival factors regulating ovarian apoptosis -- dependence on follicle differentiation

Reproduction ◽  
2002 ◽  
pp. 23-30 ◽  
Author(s):  
E Markstrom ◽  
ECh Svensson ◽  
R Shao ◽  
B Svanberg ◽  
H Billig
Keyword(s):  
Growth Factor ◽  
Follicular Development ◽  
Antral Follicle ◽  
Short Review ◽  
Ovarian Follicles ◽  
Survival Factors ◽  
Primordial Follicles ◽  
Survival Factor ◽  
Fetal Ovary

Only a minute fraction of the ovarian follicles present in a fetal ovary will complete the path to ovulation. Most of the follicles will undergo atresia, a hormonally controlled apoptotic process. Apoptosis occurs at each stage of follicular development and there is a marked reduction in the number of follicles present at birth. Stage-dependent mechanisms of follicle survival can be postulated to achieve co-ordinated development, leading to ovulation of a small fraction of follicles. Indeed, hormone and growth factor regulation of follicular atresia is stage-specific. This short review considers the factors that promote survival of ovarian follicles throughout development, including endocrine, locally produced and intracellular mediators, as exemplified mainly by follicular development in rodents. In primordial follicles, oocyte apoptosis is considered to be the cause of subsequent follicle degeneration. In slow-growing preantral follicles, FSH is not a survival factor, but some locally produced growth factors are. Progression to the antral follicle stage is probably the most critical stage of follicle development in vivo, and FSH is a major survival factor at this stage. In addition, insulin-like growth factor I and interleukin 1beta are potent survival factors for cultured rat follicles at the antral stage. Preovulatory follicles express receptors for LH, and both of the gonadotrophins are survival factors at this stage. Relatively little is known about the period between the LH surge and ovulation; however, it has been suggested that at this stage progesterone acts as a survival factor.

scholarly journals Kisspeptin level in the aging ovary is regulated by the sympathetic nervous system

2017 ◽  
Vol 232 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Daniela Fernandois ◽  
Gonzalo Cruz ◽  
Eun Kyung Na ◽  
Hernán E Lara ◽  
Alfonso H Paredes
Keyword(s):  
Adrenergic Receptor ◽  
Follicular Development ◽  
Sympathetic Nerves ◽  
Female Rats ◽  
Reproductive Aging ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Primordial Follicles ◽  
Follicular Cyst

Previous work has demonstrated that the increase in the activity of sympathetic nerves, which occurs during the subfertility period in female rats, causes an increase in follicular cyst development and impairs follicular development. In addition, the increase in ovarian sympathetic activity of aged rats correlates with an increased expression of kisspeptin (KISS1) in the ovary. This increase in KISS1 could participate in the decrease in follicular development that occurs during the subfertility period. We aimed to determine whether the blockade of ovarian sympathetic tone prevents the increase in KISS1 expression during reproductive aging and improves follicular development. We performed 2 experiments in rats: (1) an in vivo blockade of beta-adrenergic receptor with propranolol (5.0 mg/kg) and (2) an ovarian surgical denervation to modulate the sympathetic system at these ages. We measured Kisspeptin and follicle-stimulating hormone receptor (FSHR) mRNA and protein levels by qRT-PCR and western blot and counted primordial, primary and secondary follicles at 8, 10 and 12 months of age. The results showed that ovarian KISS1 decreased but FSHR increased after both propranolol administration and the surgical denervation in rats of 8, 10 and 12 months of age. An increase in FSHR was related to an increase in the number of smaller secondary follicles and a decreased number of primordial follicles at 8, 10 and 12 months of age. These results suggest that intraovarian KISS1 is regulated by sympathetic nerves via a beta-adrenergic receptor and participates locally in ovarian follicular development in reproductive aging.

scholarly journals Transactivation of the Epidermal Growth Factor Receptor Is Involved in the Lutropin Receptor-Mediated Down-Regulation of Ovarian Aromatase Expression in Vivo

2010 ◽  
Vol 24 (3) ◽  
pp. 552-560 ◽  
Author(s):  
Nebojsa Andric ◽  
Mika Thomas ◽  
Mario Ascoli
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mouse Models ◽  
Growth Factor Receptor ◽  
Follicular Development ◽  
Down Regulation ◽  
Aromatase Expression ◽  
Epidermal Growth

Abstract Ovarian follicular development and differentiation is characterized by dramatic changes in aromatase (Cyp19a1) expression. In preovulatory follicles, activation of the FSH receptor increases aromatase expression until the surge of LH decreases it. Here we provide in vivo evidence that down-regulation of Cyp19a1 by the LH surge requires efficient signaling through the epidermal growth factor receptor (EGFR). The human chorionic gonadotropin (hCG)-induced down-regulation of Cyp19a1 expression in the two different mouse models with inactivating mutations of the EGFR (wa2 and velvet) is impaired but not abolished. The hCG-induced phosphorylation of ovarian ERK1/2, expression of C/EBPβ, and the phosphorylation of Connexin43 (two downstream targets of ERK1/2 action) are also decreased in these two mouse models. In contrast, disruption of EGFR signaling does not have any affect on the hCG-induced phosphorylation of cAMP response element-binding protein or AKT. This study provides the first in vivo evidence linking the LH receptor, the EGFR, and ERK1/2 as sequential components of a pathway that regulates ovarian Cyp19a1 expression.

Follistatin but not α or βA inhibin subunit mRNA is expressed in ovine fetal ovaries in late gestation

1994 ◽  
Vol 13 (1) ◽  
pp. 1-9 ◽  
Author(s):  
R Braw-Tal ◽  
D J Tisdall ◽  
N L Hudson ◽  
P Smith ◽  
K P McNatty
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Cell Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Late Gestation ◽  
Follicle Growth ◽  
Primordial Follicles ◽  
Fetal Ovary ◽  
Ovine Fetal

ABSTRACT The aim of this study was to investigate the sites of follistatin and α and βA inhibin mRNA expression in the ovaries of female sheep fetuses at 90, 100, 120 and 135 days of gestation (term=day 147). At 90 and 100 days primordial follicles were formed, followed by the appearance of primary follicles at 100 days of gestation. At days 120 and 135, primordial, primary and preantral (i.e. secondary) follicles were present in the ovaries, but antral (i.e. tertiary) follicles were not observed at any of these gestational ages. Two Booroola genotypes were studied: homozygous carriers (BB) and non-carriers (++) of the fecundity gene (FecB). Irrespective of genotype no specific hybridization of the α and βA inhibin riboprobes was detected in any ovarian cells at days 90, 100, 120 or 135 of gestation. In control mature ovaries, on the other hand, strong hybridization in the granulosa cells of antral follicles was observed. In contrast to α and βA inhibin, follistatin antisense (but not sense) riboprobes hybridized specifically to the granulosa cells of preantral follicles with two or more layers of cells at days 120 and 135 of gestation. Moreover, hybridization was also evident in the cells of the ovarian rete at days 120 and 135, but not at 90 or 100 days. No follistatin mRNA expression was observed in the granulosa cells of primordial or primary follicles or in any other ovarian cell type at any of the gestational ages examined. No FecB-specific differences in follistatin expression were noted with respect to stage of preantral follicular development and there were no obvious differences in the intensity of expression. These results show that follistatin mRNA is expressed specifically in the granulosa cells and intraovarian rete. Expression of follistatin in rete cells was coincident with the increasing numbers of growing follicles within the fetal ovary, indicating that rete cell function may have a role in the ontogeny of early follicular growth. Our results suggest that follistatin and α and βA inhibin may not be important for the initiation of follicle growth in the sheep ovary, since these genes are not expressed during the transformation of a primordial follicle to a primary structure. However, the evidence for follistatin mRNA expression in the ovine fetal ovary implies that this hormone is likely to play a role during the early stages of follicle growth.

scholarly journals Placental Growth Factor Is Required for Ovulation, Luteinization, and Angiogenesis in Primate Ovulatory Follicles

Endocrinology ◽  
2017 ◽  
Vol 159 (2) ◽  
pp. 710-722 ◽  
Author(s):  
Hannah R Bender ◽  
Heidi A Trau ◽  
Diane M Duffy
Keyword(s):  
Growth Factor ◽  
Granulosa Cell ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Placental Growth Factor ◽  
Vascular Endothelial ◽  
Follicle Rupture ◽  
Ovulatory Follicles ◽  
Endothelial Growth Factor

Abstract Placental growth factor (PGF) is member of the vascular endothelial growth factor (VEGF) family of angiogenesis regulators. VEGFA is an established regulator of ovulation and formation of the corpus luteum. To determine whether PGF also mediates aspects of ovulation and luteinization, macaques received gonadotropins to stimulate multiple follicular development. Ovarian biopsies and whole ovaries were collected before (0 hours) and up to 36 hours after human chorionic gonadotropin (hCG) administration to span the ovulatory interval. PGF and VEGFA were expressed by both granulosa cells and theca cells. In follicular fluid, PGF and VEGFA levels were lowest before hCG. PGF levels remained low until 36 hours after hCG administration, when PGF increased sevenfold to reach peak levels. Follicular fluid VEGFA increased threefold to reach peak levels at 12 hours after hCG, then dropped to intermediate levels. To explore the roles of PGF and VEGFA in ovulation, luteinization, and follicular angiogenesis in vivo, antibodies were injected into the follicular fluid of naturally developed monkey follicles; ovariectomy was performed 48 hours after hCG, with ovulation expected about 40 hours after hCG. Intrafollicular injection of control immunoglobulin G resulted in no retained oocytes, follicle rupture, and structural luteinization, including granulosa cell hypertrophy and capillary formation in the granulosa cell layer. PGF antibody injection resulted in oocyte retention, abnormal rupture, and incomplete luteinization, with limited and disorganized angiogenesis. Injection of a VEGFA antibody resulted in oocyte retention and very limited follicle rupture or structural luteinization. These studies demonstrate that PGF, in addition to VEGFA, is required for ovulation, luteinization, and follicular angiogenesis in primates.

scholarly journals Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3329-3343 ◽  
Author(s):  
Jinhwan Lim ◽  
Brooke N. Nakamura ◽  
Isaac Mohar ◽  
Terrance J. Kavanagh ◽  
Ulrike Luderer
Keyword(s):  
Oxidative Stress ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Glutamate Cysteine Ligase ◽  
Primordial Follicles ◽  
Age Related ◽  
Oxidative Protein Damage ◽  
Rate Of Decline ◽  
The One ◽  
Damage Marker

Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development.

359 ICSI AND ACTIVATION OF OOCYTES RECOVERED FROM TRANSITIONAL AND CYCLING MARES

2006 ◽  
Vol 18 (2) ◽  
pp. 286 ◽  
Author(s):  
T. Suh ◽  
S. Purcell ◽  
G. Seidel Jr
Keyword(s):  
Growth Factor ◽  
Polar Body ◽  
Follicular Development ◽  
Transitional Period ◽  
Developmental Competence ◽  
Blastocyst Development ◽  
Cleavage Rate ◽  
First Polar Body

Ovarian follicular development in mares during the transitional period before the breeding season leads to an accumulation of antral follicles of various sizes. The quality of oocytes at this stage may be compromized until the first seasonal ovulation. In this study, we evaluated the developmental competence of oocytes recovered from transitional and cyclic mares, and the effect of zygote activation after intracytoplasmic sperm injection (ICSI). A 2 × 2 × 2 factorial experiment consisting of oocytes from transitional and cyclic mares, two follicle sizes (10 to 20 and 20+ mm), and two treatments (control and activated) was conducted. Follicular oocytes of 14 mares were aspirated in March and April (transitional) and May to July (cyclic) five times per each period at 10-day intervals, without use of hCG. Oocytes aspirated from mares were matured in vitro in a defined medium similar to SOF plus FSH, LH, epidermal growth factor (EGF), insulin-like growth factor (IGF), estradiol (E2), prostaglandin (P4) and 10% FCS, for 30 ± 1 h under 5% CO2 in air at 38.5°C; oocytes with a first polar body were used for ICSI. Motile sperm from frozen-thawed semen were used for sperm injection with a piezo-driven pipet. For activation after ICSI, presumptive zygotes were cultured in G1.3 containing 0.02 µM phorbol 12-myristate 13-acetate (PMA) for 2 h, and then in 2 mM 6-dimethylaminopurine (6-DMAP) for 3 h under 6% CO2 in air at 38.5°C. Zygotes were cultured in 50 µL drops of DMEM/F12 containing 10% FCS for 9 days at 38.5°C in 5% CO2/5% O2/90% N2. Medium was replaced every 3 days. Cleavage and blastocyst rates were calculated based on non-degenerating injected oocytes. Data were analyzed by Fisher's exact test. A total of 115 and 78 oocytes were recovered from cyclic and transitional mares. Average maturation rates to MII in the respective groups were 76.5 and 65.4%, respectively (P < 0.07), and those of 10 to 20 and 20+ mm follicle groups were 70.6 and 80.0%, respectively (P > 0.05). The average cleavage rate in cyclic mares was higher than in transitional mares, and that of the activated group averaged over follicle sizes was higher than that of controls (P < 0.05; Table 1); those of 10 to 20 and 20+ mm follicle groups were not different (P < 0.05; Table 1). Blastocyst rates per oocyte within main effects were not different (P < 0.05; Table 1). Oocytes from transitional mares had lower cleavage rates than those of cyclic mares, but blastocyst development was similar. Activation of zygotes clearly improved cleavage rates of in vivo-derived immature equine oocytes after ICSI. Table 1. Main effect means of responses after ICSI

ACCUMULATION OF LUTEINIZING HORMONE, OESTRADIOL AND ANDROSTENEDIONE BY SHEEP OVARIAN FOLLICLES IN VIVO

1981 ◽  
Vol 91 (1) ◽  
pp. 99-109 ◽  
Author(s):  
K. P. McNATTY ◽  
CAROLYN DOBSON ◽  
MARION GIBB ◽  
LINDA KIEBOOM ◽  
D. C. THURLEY
Keyword(s):  
Antral Follicle ◽  
Ovarian Follicles ◽  
Time Intervals ◽  
Peripheral Plasma ◽  
Temporal Relationships ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Secretion Rates ◽  
Large Antral Follicle

The temporal relationships between the levels of LH in peripheral plasma and in follicular fluid of ovarian follicles in anaesthetized sheep were investigated for a 10-h period after a single i.m. injection of LH releasing hormone (LH-RH; 100 μg). The ovarian secretion rates of oestradiol and androstenedione and the levels of these steroids accumulating in different sized follicles at varying time-intervals after the LH-RH injection were also compared. The data show that the rates at which pituitary LH enters and leaves the intrafollicular fluid-filled spaces are substantially slower than those of peripheral blood. Two hours after LH-RH injection the levels of LH in plasma had increased from 1 to 200 ng/ml, whereas in the follicle the levels remained at approximately 2 ng/ml. Ten hours after the LH-RH injection, the levels of LH in plasma had returned to basal values (∼1·4 ng/ml) but in both small and large follicles the levels of LH (∼20 ng/ml) were comparable to those present in similar sized follicles 4 h earlier. The data also indicate that more than 90% of the oestradiol produced by a large antral follicle (≥5 mm diameter) probably enters the bloodstream without first accumulating within the follicular antrum. Finally it is concluded that the clearance of the small amount of oestradiol which does accumulate in the follicular antrum is negligible compared with the clearance of this hormone from peripheral plasma.

scholarly journals In vitro and in vivo regulation of follicular formation and activation in cattle

2011 ◽  
Vol 23 (1) ◽  
pp. 15 ◽  
Author(s):  
Joanne E. Fortune ◽  
Ming Y. Yang ◽  
Wanzirai Muruvi
Keyword(s):  
Follicular Development ◽  
First Trimester ◽  
Vascular Endothelial ◽  
Second Trimester ◽  
Primordial Follicles ◽  
Kit Ligand ◽  
Secondary Stage ◽  
Endothelial Growth Factor

The establishment of a stockpile of non-growing, primordial follicles and its gradual depletion through activation of primordial follicles are essential processes for female fertility. However, the mechanisms that regulate follicle formation, the activation of primordial follicles to begin growth and the primary-to-secondary follicle transition are poorly understood, especially in domestic animals and primates. The authors’ laboratory is engaged in studying early stages of follicular development in cattle and this review summarises the progress to date. Bovine follicles begin to form in fetal ovaries around the beginning of the second trimester of pregnancy (about Day 90), but the first activated, primary follicles do not appear until after Day 140. Bovine fetal ovaries produce steroids and production is highest during the first trimester. In vitro, oestradiol and progesterone inhibit follicle formation and acquisition by newly formed follicles of the capacity to activate. Meiotic arrest of the oocyte in the diplotene stage of first prophase does not occur until after follicle formation and is correlated with acquisition of the capacity to activate. This may explain the gap between follicle formation and appearance of the first activated follicles. Once capacity to activate has been acquired, it seems likely that activation in vivo is controlled by the balance between stimulators and inhibitors of activation. Insulin and kit ligand stimulate and anti-Müllerian hormone (AMH) inhibits activation in vitro. Few bovine follicles transition from the primary to the secondary stage in vitro, but this transition is increased by medium supplements, testosterone and vascular endothelial growth factor (VEGF).

scholarly journals The mouse Balbiani body maintains primordial follicle quiescence via RNA storage

2020 ◽  
Author(s):  
Lei Lei ◽  
Kanako Ikami ◽  
Haley Abbott ◽  
Shiying Jin
Keyword(s):  
Ovarian Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Primordial Follicles ◽  
Mrna Decapping ◽  
Balbiani Body ◽  
Mrna Capping ◽  
Capping Enzyme ◽  
Decapping Enzyme

AbstractIn mammalian females, the transition between quiescent primordial follicles and follicular development is critical for maintaining ovarian function and reproductive longevity. In primary oocytes of mouse quiescent primordial follicles, Golgi complexes are organized into a spherical structure, the Balbiani body. Here, we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1A. Proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological disassembly of the B-body triggers translation of stored mRNAs and activates primordial follicles in culture and in vivo mouse model. Thus, primordial follicle quiescence is maintained by the B-body, and translationally inactive B-body-stored mRNAs may be regulated by 5’-capping.

scholarly journals Identification of the chemokine CCL28 as a growth and survival factor for human hematopoietic stem and progenitor cells

Blood ◽  
2013 ◽  
Vol 121 (19) ◽  
pp. 3838-3842 ◽  
Author(s):  
Christine Karlsson ◽  
Aurélie Baudet ◽  
Natsumi Miharada ◽  
Shamit Soneji ◽  
Rajeev Gupta ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Growth And Survival ◽  
Functional Integrity ◽  
Survival Factor ◽  
Key Points ◽  
Stem And Progenitor Cells

Key Points Chemokine (C-C motif) ligand 28 (CCL28) is a novel growth factor for human hematopoietic stem and progenitor cells. CCL28 supports the in vitro and in vivo functional integrity of cultured primitive hematopoietic cells.

Sign in / Sign up

Export Citation Format

Share Document