scholarly journals NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Bredford Kerr ◽  
Cecilia Garcia-Rudaz ◽  
Mauricio Dorfman ◽  
Alfonso Paredes ◽  
Sergio R Ojeda
Keyword(s):  
Ovarian Development ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Tyrosine Kinase Receptors ◽  
Wild Type ◽  
Mouse Ovary ◽  
Cell Cycle Protein ◽  
Primordial Follicles ◽  
A Cell ◽  
The Common

Recent studies have demonstrated that neurotrophins (NTs) and their NTRK tyrosine kinase receptors, thought to be exclusively required for the development of the nervous system, are also involved in controlling ovarian development. Here, we show that primordial follicle formation is decreased in the absence of nerve growth factor (NGF) or its receptor NTRK1, and in the absence of NTRK2, the receptor for neurotrophin-4 (NTF4) and brain-derived neurotrophic factor (BDNF). This deficiency is not due to premature oocyte loss, because the ovaries ofNtrk1−/−andNtrk2−/−mice do not show an increased rate of oocyte death antedating the initiation of folliculogenesis. Moreover, exposure of NGF-deficient ovaries to NGF rescues the defect in follicular assembly, if NTRK1 receptors are present, suggesting that the absence of NTs causes a delay, and not an irretrievable loss, of follicle formation. Both the number of secondary follicles and FSH receptor (FSHR) expression are diminished inNtrk1- andNtrk2-null ovaries, but not in ovaries lacking the common NT receptor NGFR. Transient exposure of wild-type ovaries to NTF4 increasesFshrgene expression and enhances the ability of the ovary to respond to FSH with formation of cyclin D2, a cell cycle protein mediating the proliferative actions of FSH in the ovary. These results indicate that both NTRK1 and NTRK2 receptors are necessary for the timely assembly of primordial follicles and for sustaining early follicular development. They also suggest that a mechanism by which NTRK2 receptors facilitate subsequent follicle development is by inducing the formation of functional FSHR.

scholarly journals 202.Estrogen actions on follicle formation and early follicle development

2004 ◽  
Vol 16 (9) ◽  
pp. 202
Author(s):  
K. L. Britt ◽  
P. K. Saunders ◽  
S. J. McPherson ◽  
M. L. Misso ◽  
E. R. Simpson ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proliferating Cell Nuclear Antigen ◽  
Leydig Cells ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Nuclear Antigen ◽  
Proliferative Index ◽  
Mouse Ovary ◽  
Primordial Follicles ◽  
Proliferating Cell

Estradiol 17 beta (E2) effects late follicular development whilst primordial follicle formation and early activation are thought to be independent of E2. To test this hypothesis we compared numbers of primordial and primary follicles in wildtype and E2 deficient ArKO mice, and the immunohistochemical staining or mRNA expression of Mullerian inhibiting substance (MIS), Wilms tumour 1 (WT-1), and growth differentiation factor (GDF9), known to effect early follicular differentiation. Proliferating cell nuclear antigen (PCNA) staining was a marker of proliferative index. The effects of E2 replacement for 3 wk in 7 wk old ArKO and wildtype mice on these parameters were also tested. We used unbiased, assumption-free stereological methods for quantification of early follicular numbers in the mouse ovary (1). ArKO mice had reduced numbers of primordial and primary follicles compared to wildtype (63%, p<0.001 and 60%, p=0.062 of Wt respectively). This reduction was not corrected by E2 treatment, suggesting that E2 effects the initial formation or activation of primordial follicles. There was a significant increase in the diameters of the oocytes in primordial follicles of ArKO mice compared to wildtype. There were no differences in the immunostaining of MIS, WT-1 and PCNA in primordial and primary follicles between wildtype and ArKO mice. The only difference was as a consequence of Sertoli and Leydig cells in ovaries of ArKO mice. GDF9 mRNA expression was markedly increased in ArKO ovaries. E2 treatment restored the ovarian follicular morphology, and consequently the immunostaining patterns, but had no effect on early follicle numbers. In conclusion, E2 has a role in controlling the size of the oocyte and primordial follicle pools in mice. Supported by NH&MRC RegKey #241000 and 198705. (1) Britt and Myers (2004) Reproduction 127,:569–580.

scholarly journals Ovarian development in intrauterine growth-retarded and normally developed piglets originating from the same litter

Reproduction ◽  
2003 ◽  
pp. 249-258 ◽  
Author(s):  
P Da Silva-Buttkus ◽  
R van den Hurk ◽  
ER te Velde ◽  
MA Taverne
Keyword(s):  
Body Weight ◽  
Ovarian Development ◽  
Cell Activity ◽  
Follicular Development ◽  
Follicle Cell ◽  
Epidemiological Studies ◽  
Image Analysis System ◽  
Ovarian Mass ◽  
Primordial Follicles ◽  
Intrauterine Growth

Epidemiological studies in humans linking adult disease to growth in utero indicate that prenatal life is a critical period for the appropriate development of the reproductive axis. The aim of this study was to compare ovarian development in intrauterine growth-retarded and normally grown piglets originating from the same litter. Intrauterine growth-retarded piglets (runts) were identified on the basis of statistical analysis of the birth weight distribution within each litter. At birth, ovaries were collected from runt piglets (n=14) and their respective mean weight (normal, n=14) littermates. Ovaries were weighed and fixed, and development of ovarian germ cells was quantified in haematoxylin-eosin-stained paraffin wax sections using an image analysis system. Germ cell loss, using an in situ TdT-mediated dUTP nick-end labelling (TUNEL) assay for DNA fragmentation, and follicle cell activity, using immunohistochemistry to demonstrate vimentin, were studied in ovarian sections. At birth, body weight and absolute ovarian mass were significantly lower in runt piglets compared with their respective normally grown littermates (body weight: 733+/-38.5 versus 1530+/-39.7 g; ovarian mass: 51+/-3.0 versus 108+/-9.6 mg; P<0.001 for both). In the ovary, the proportion of nests of oogonia, the number of oocytes and TUNEL-positive cells, and the localization and intensity of vimentin immunoreactivity were not different between runt and normal littermates. However, runt piglets had more primordial follicles (268+/-18.6 versus 235+/-20.1 per mm(2) of cortex; P<0.05), fewer primary follicles (11+/-2.0 versus 20+/-3.0 per mm(2) of cortex; P<0.001) and no secondary follicles compared with normal piglets. These findings indicate that intrauterine growth retardation delayed follicular development in pig ovaries at birth.

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 207 OOCYTE SURVIVAL AND FOLLICULAR DEVELOPMENT IN Fas-KNOCKOUT AND KIT-DEFICIENT DOUBLE MUTANT MICE

2005 ◽  
Vol 17 (2) ◽  
pp. 254
Author(s):  
M. Moniruzzaman ◽  
K.O. Sakamaki ◽  
Y. Akazawa ◽  
T. Miyano
Keyword(s):  
Germ Cells ◽  
Double Mutant ◽  
Death Receptor ◽  
Follicular Development ◽  
The Other ◽  
Wild Type ◽  
Severe Combined Immune Deficiency ◽  
Growth And Survival ◽  
Primordial Follicles ◽  
Student’S T

Growth factors and cytokines regulate survival and growth of mammalian oocytes via their cognate receptors. Among those receptors, KIT, a receptor tyrosine kinase, has been thought of as an essential molecule for growth and survival of oocytes and for follicular development. The defect of KIT-mediated signals leads to the loss of oocytes and impairment of follicular development. Fas is a member of the death receptor family inducing apoptosis; it expresses in the ovary. In a previous study (Sakata et al. 2003 Cell Death Differ. 10, 676–86), we generated KIT-deficient and Fas-knockout double mutant (Wv/Wv:Fas−/−) mice to study the relation between Fas and KIT signaling in germ cell apoptosis. To further understand the role of KIT in oocyte survival and follicular development, we examined the ovaries of Wv/Wv and Wv/Wv:Fas−/− in comparison to those of C57BL/6 (wild type) mice. We also examined the possibility of overcoming the deleterious effects of KIT deficiency by ovarian allotransplantation. One ovary of each mouse was fixed for immediate histological examination and the other was transplanted under the kidney capsule of a female SCID (severe combined immune deficiency) mouse. Ovaries and recovered grafts were fixed, embedded, serially sectioned at 5 μm, stained with hematoxylin and eosin, and examined under a microscope. Oocytes were counted in every section where the nucleus was seen, avoiding double counting in adjacent sections. Mean (with standard deviation) numbers of oocytes per graft or ovary were compared using Student's t-test. At 13 days post-coitum (dpc), ovaries of Wv/Wv fetuses contained 1104.3 ± 118.8 (n = 4) germ cells which was significantly (P < 0.05) lower than those of wild-type mice. However, at 16 dpc (n = 6) and 2-days old (n = 6), ovaries did not contain any germ cells/oocytes. After allotransplantation of the ovaries (n = 6) from Wv/Wv fetuses (13 dpc) for 2 weeks, all of the germ cells disappeared. When the ovaries from 2-day-old Wv/Wv mice (n = 6) were allotransplanted for 12 days, no oocytes appeared. On the other hand, transplanted ovaries from C57BL/6 fetuses (13 dpc) contained 2162.0 ± 97.3 (n = 6) oocytes after 2 weeks. In those ovaries, 4.7 ± 1.6% follicles developed to secondary follicles which contained growing oocytes. Importantly, ovaries of 2-day-old Wv/Wv:Fas−/− mice (n = 4) contained 1936.0 ± 245.0 oocytes (64.0 ± 10.0% of wild-type mice), and 14-day-old mice (n = 4) still contained 911.3 ± 106.3 follicles in which 28.6 ± 6.0% and 11.4 ± 3.2% follicles developed to primary and secondary follicles, respectively. These results indicate that oocyte death due to KIT-deficiency can not be rescued by ovarian transplantation in SCID mice, and that the Fas-knockout condition partially prevents the death of oocytes induced by KIT-deficiency, and primordial follicles develop in this condition.

Transgenerational inheritance of ovarian development deficiency induced by maternal diethylhexyl phthalate exposure

2015 ◽  
Vol 27 (8) ◽  
pp. 1213 ◽  
Author(s):  
Xi-Feng Zhang ◽  
Teng Zhang ◽  
Zhe Han ◽  
Jing-Cai Liu ◽  
Yu-Ping Liu ◽  
...  
Keyword(s):  
Ovarian Development ◽  
Primordial Follicle ◽  
Abnormal Development ◽  
Endogenous Hormones ◽  
Transgenerational Inheritance ◽  
Primordial Follicles ◽  
Diethylhexyl Phthalate ◽  
Meiotic Progression ◽  
Pregnant Mice ◽  
Dehp Exposure

Diethylhexyl phthalate (DEHP) is a widely used industrial additive for increasing plastic flexibility. It disrupts the physiological functions of endogenous hormones and induces abnormal development of mammals. The objectives of the present study were to evaluate the effects of DEHP exposure on ovarian development of pregnant mice and whether the effects are inheritable. We found that the synthesis of oestradiol in pregnant mice after DEHP exposure was significantly decreased, and that the first meiotic progression of female fetal germ cells was delayed. Furthermore, the DNA methylation level of Stra8 was increased and the expression levels of Stra8 were significantly decreased. An accelerated rate of follicle recruitment in F1 mice was responsible for the depletion of the primordial-follicle pool. Maternal DEHP exposure also significantly accelerated the recruitment of primordial follicles in F2 mice. In conclusion, our results indicated that maternal DEHP exposure induced ovarian development deficiency, which was transgenerational in mice.

scholarly journals Anti-Müllerian hormone overexpression restricts preantral ovarian follicle survival

2018 ◽  
Vol 237 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Michael W Pankhurst ◽  
Rebecca L Kelley ◽  
Rachel L Sanders ◽  
Savana R Woodcock ◽  
Dorothy E Oorschot ◽  
...  
Keyword(s):  
Reproductive Output ◽  
Ovarian Follicle ◽  
Follicle Stimulating Hormone ◽  
Primordial Follicle ◽  
Slight Reduction ◽  
Wild Type ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Primordial Follicle Activation ◽  
Ovarian Folliculogenesis

Anti-Müllerian hormone (AMH) is an ovarian regulator that affects folliculogenesis. AMH inhibits the developmental activation of the dormant primordial follicles and the oocyte within. In more mature follicles, AMH reduces granulosa cell sensitivity to follicle-stimulating hormone (FSH). We examined the effects of AMH overexpression on the stages of ovarian folliculogenesis, and the development of embryos, with a transgenic mouse that overexpresses human AMH in central nervous system neurons under the control of the mouse Thy1.2 promoter (Thy1.2-AMH Tg mice). These mice are severely sub-fertile, despite relatively normal ovulation rates. The embryos of Thy1.2-AMHTg females exhibited delayed preimplantation development and extensive mid-gestation fetal resorption. Young Thy1.2-AMHTg mouse ovaries exhibited only a slight reduction in the rate of primordial follicle activation but large declines in the number of developing follicles surviving past the primary stage. It was expected that Thy1.2-AMHTg mice would retain more primordial follicles as they aged, but at 5 months, their number was significantly reduced relative to wild-type females. These data indicate that moderate elevations in AMH levels can severely restrict reproductive output and the number of developing follicles in the ovary. This evidence suggests that early antral follicles are a target for AMH signaling, which may regulate early follicle survival.

Supplementation of granulosa cells conditioned medium with pyruvate and testosterone could improve early follicular development in cultured 1-day-old mouse ovaries

Zygote ◽  
2021 ◽  
pp. 1-8
Author(s):  
Mohammad Jafari Atrabi ◽  
Parimah Alborzi ◽  
Vahid Akbarinejad ◽  
Rouhollah Fathi
Keyword(s):  
Conditioned Medium ◽  
Ovarian Tissue ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Primordial Follicles ◽  
Patients With Cancer ◽  
Primordial Follicle Activation ◽  
Follicle Activation

Summary In vitro activation of primordial follicles could serve as a safe method to preserve fertility in patients with cancer subjected to ovarian tissue cryopreservation during oncotherapy, however the culture medium for this purpose requires to be optimized. Granulosa cell conditioned medium (GCCM) has been recognized to enhance primordial follicle activation and the present study was conducted to understand whether addition of pyruvate, a combination of insulin, transferrin and selenium (ITS) or testosterone to GCCM could improve its efficiency in this regard. To this end, 1-day-old mouse ovaries were cultured in four different media including CON (control; containing GGCM only), PYR (containing GCCM plus pyruvate), ITS (containing GCCM plus ITS) or TES (containing GCCM plus testosterone) for 11 days. Furthermore, follicular dynamics and gene expression of factors involved in follicular development were assessed using histological examination and RT-PCR, respectively, on days 5 and 11 of culture. Pyruvate decreased follicular activation, but it enhanced the progression of follicles to the primary stage. Moreover, it upregulated Bmp15 and Cx37 (P < 0.05). In the ITS group, activation of follicles was not affected and total number of follicles was reduced by day 11 of culture. Additionally, ITS downregulated Pi3k, Gdf9, Bmp15 and Cx37 (P < 0.05). Although testosterone did not affect primordial follicle activation, it enhanced the development of follicles up to the preantral stage (P < 0.05). Furthermore, testosterone inhibited the expression of Pten but stimulated the expression of Gdf9 and Cx37 (P < 0.05). In conclusion, the present study revealed that inclusion of pyruvate and testosterone into GCCM could enhance the early development of follicles in cultured 1-day-old mouse ovaries.

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 Testosterone Induces Redistribution of Forkhead Box-3a and Down-Regulation of Growth and Differentiation Factor 9 Messenger Ribonucleic Acid Expression at Early Stage of Mouse Folliculogenesis

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 774-782 ◽  
Author(s):  
Jun-Ling Yang ◽  
Chun-Ping Zhang ◽  
Lei Li ◽  
Lin Huang ◽  
Shao-Yang Ji ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Early Stage ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Phosphatidylinositol 3 Kinase ◽  
Primordial Follicles ◽  
Messenger Ribonucleic Acid ◽  
Forkhead Box ◽  
Differentiation Factor ◽  
Primordial Follicle Activation

Increasing evidence has shown that excess androgen may be a main cause of polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen action on the ovary is unclear. To investigate the possible impacts of androgen on early follicular development, neonatal mouse ovaries mainly containing primordial follicles were cultured with testosterone. We demonstrated that the number of primary follicles was increased after 10 d culture with testosterone treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from oocyte nuclei to cytoplasm, which might be a key step for primordial follicle activation. Interestingly, testosterone was also capable of down-regulating growth and differentiation factor-9 expression via its receptor. In summary, we infer that intraovarian excess androgen in PCOS might result in excess early follicles by inducing oocyte Foxo3a translocation and follicular arrest by down-regulating growth and differentiation factor-9 expression.

scholarly journals Hormonal suppression for fertility preservation in males and females

Reproduction ◽  
2008 ◽  
Vol 136 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Marvin L Meistrich ◽  
Gunapala Shetty
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Ovarian Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Cytotoxic Agents ◽  
Cytotoxic Therapy ◽  
Primordial Follicles ◽  
Beneficial Effects ◽  
Gnrh Analogs

Methods to restore fertility of men and women sterilized by medical treatments and environmental toxicant exposures are under investigation. Rendering spermatogenesis and ovarian follicular development kinetically quiescent by suppression of gonadotropins has been proposed to protect them from damage by cytotoxic therapy. Although the method fails to protect the fertility of male mice and monkeys, gonadotropin and testosterone suppression in rats before or after cytotoxic therapy do enhance the recovery of spermatogenesis. However, the mechanism involves not the induction of quiescence but rather the reversal, by suppression of testosterone, of a block in differentiation of surviving spermatogonia caused by damage to the somatic environment. In men, only one of eight clinical trials was successful in protecting or restoring spermatogenesis after cytotoxic therapy. In women, protection of primordial follicles in several species from damage by cytotoxic agents using GnRH analogs has been claimed; however, only two studies in mice appear convincing. The protection cannot involve the induction of quiescence in the already dormant primordial follicle but may involve direct effects of GnRH analogs or indirect effects of gonadotropin suppression on the whole ovary. Although numerous studies in female patients undergoing chemotherapy indicate that GnRH analogs might be protective of ovarian function, none of the studies showing protection were prospective randomized clinical trials and thus they are inconclusive. Considering interspecies differences and similarities in the gonadal sensitivity to cytotoxic agents and hormones, mechanistic studies are needed to identify the specific beneficial effects of hormonal suppression in select animal models that may be applicable to humans.

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