scholarly journals The Role of Anti-Müllerian Hormone (AMH) During Follicle Development in a Monovulatory Species (Sheep)

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4533-4543 ◽  
Author(s):  
Bruce K. Campbell ◽  
M. Clinton ◽  
R. Webb
Keyword(s):  
Functional Relationship ◽  
Primordial Follicle ◽  
Active Immunization ◽  
Follicle Development ◽  
Antral Follicles ◽  
Therapeutic Value ◽  
Clinical Interest

Knockout studies in mice have suggested that anti-Müllerian hormone (AMH) modulates primordial follicle recruitment and the response of growing follicles to FSH. Little is known of the physiology of AMH in monovular species, despite intense clinical interest in this factor. Using sheep as a model, we sought to investigate the functional role of AMH in modulating follicle development in monovular species. In contrast to the rodent, the results indicate that AMH does not affect the rate of primordial follicle recruitment but appears to regulate the rate at which follicles progress through the gonadotropin-responsive phase, during which it is maximally expressed. Thus, knockdown of AMH bioactivity by active immunization lead to a decline in the population of gonadotropin-responsive preantral and small antral follicles (P < 0.01) and increases in both the number of gonadotropin-dependent antral follicles (P < 0.01) and ovulation rate (P < 0.05). These in vivo findings were consistent with the results of other studies examining the pattern of expression of AMH, which was negatively correlated with aromatase (P < 0.001), and in vitro supplementation experiments, which supported an inhibitory role for AMH in modulating the response of both theca and granulosa cells to LH and FSH, respectively. The elucidation of a functional relationship between AMH and LH-stimulated thecal androgen production may be significant in terms of the etiology of common forms of anovulatory infertility in women. Furthermore, the observed increase in both the number of recruitable antral follicles and ovulatory quota in response to AMH knockdown may have therapeutic value in women who respond poorly to ovarian stimulation.

scholarly journals Development of Primordial Follicles in the Hamster: Role of Estradiol-17β

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1707-1716 ◽  
Author(s):  
Cheng Wang ◽  
Shyamal K. Roy
Keyword(s):  
Primordial Follicle ◽  
Serum Levels ◽  
Primordial Follicles ◽  
Ici 182,780 ◽  
Higher Doses ◽  
Estradiol 17Β ◽  
Modest Reduction

The role of E2 on primordial follicle formation was examined by treating neonatal hamsters with 1 or 2 μg estradiol cypionate (ECP) at age postnatal d 1 (P1) and P4 or by in vitro culture of embryonic d 15 (E15) ovaries with 1, 5, or 10 ng/ml estradiol-17β (E2). The specificity of E2 action was examined by ICI 182,780. One microgram of ECP maintained serum levels of E2 within the physiological range, significantly reduced apoptosis, and stimulated the formation and development of primordial follicles. In contrast, 2 μg ECP increased serum E2 levels to 400 pg/ml and had significantly less influence on primordial follicle formation. In vivo, ICI 182,780 significantly increased apoptosis and caused a modest reduction in primordial follicle formation. The formation and development of primordial follicles in vitro increased markedly with 1 ng/ml E2, and the effect was blocked by ICI 182,780. Higher doses of E2 had no effect on primordial follicle formation but significantly up-regulated apoptosis, which was blocked by ICI 182,780. CYP19A1 mRNA expression occurred by E13 and increased with the formation of primordial follicles. P4 ovaries synthesized E2 from testosterone, which increased further by FSH. Both testosterone and FSH maintained ovarian CYP19A1 mRNA, but FSH up-regulated the expression. These results suggest that neonatal hamster ovaries produce E2 under FSH control and that E2 action is essential for the survival and differentiation of somatic cells and the oocytes leading to the formation and development of primordial follicles. This supportive action of E2 is lost when hormone levels increase above a threshold.

scholarly journals In vitro and in vivo mouse follicle development in ovaries and reaggregated ovaries

Reproduction ◽  
2019 ◽  
pp. 135-148 ◽  
Author(s):  
Belinda K M Lo ◽  
Sairah Sheikh ◽  
Suzannah A Williams
Keyword(s):  
Cell Function ◽  
Somatic Cells ◽  
Primordial Follicle ◽  
Culture Technique ◽  
Fertility Treatment ◽  
Follicle Development ◽  
Ovarian Insufficiency ◽  
Host Mouse

Follicle development requires complex and coordinated interactions between both the oocyte and its associated somatic cells. In ovarian dysfunction, follicle development may be abnormal due to defective somatic cell function; for example, premature ovarian insufficiency or malignancies. Replacing defective somatic cells, using the reaggregated ovary (RO) technique, may ‘rescue’ follicle development. ROs containing mature follicles have been generated when transplanted to a host mouse to develop. We have developed a RO culture technique and the aims were to determine how follicle development differed between transplanted and cultured ROs, and the influence of ovarian age (P2 vs P6). Mouse ROs were cultured for 14 days; P2 and P6 ovaries cultured as Controls. Follicle development was compared to ROs transplanted for 14 days and ovaries from P16 and P20 mice. ROs generated from either P2 or P6 exhibited similar follicle development in culture whereas in vivo follicle development was more advanced in P6 ROs. Follicles were more developed in cultured ROs than transplanted ROs. However, follicles in cultured ROs and ovaries had smaller oocytes with fewer theca and granulosa cells than in vivo counterparts. Our results demonstrate the fluidity of follicle development despite ovary dissociation and that environment is more important to basal lamina formation and theca cell development. Furthermore, follicle development within cultured ROs appears to be independent of oocyte nest breakdown and primordial follicle formation in source ovaries. Our results highlight the need for understanding follicle development in vitro, particularly in the development of the RO technique as a potential fertility treatment.

scholarly journals The Follistatin-288 Isoform Alone Is Sufficient for Survival But Not for Normal Fertility in Mice

Endocrinology ◽  
2009 ◽  
Vol 151 (3) ◽  
pp. 1310-1319 ◽  
Author(s):  
Fuminori Kimura ◽  
Yisrael Sidis ◽  
Lara Bonomi ◽  
Yin Xia ◽  
Alan Schneyer
Keyword(s):  
Primordial Follicle ◽  
Protein Isoforms ◽  
Differential Distribution ◽  
Primordial Follicles ◽  
C Terminus ◽  
Old Females ◽  
Tgfβ Superfamily

Follistatin (FST) is a natural antagonist of activin and related TGFβ superfamily ligands that exists as three protein isoforms differing in length at the C terminus. The longest FST315 isoform is found in the circulation, whereas the shortest FST288 isoform is typically found in or on cells and tissues, and the intermediate FST303 isoform is found in gonads. We recently demonstrated that the FST isoforms have distinct biological actions in vitro that, taken together with the differential distribution, suggests they may also have different roles in vivo. To explore the specific role of individual FST isoforms, we created a single-isoform FST288-only mouse. In contrast to the neonatal death of FST global knockout mice, FST288-only mice survive to adulthood. Although they appear normal, FST288-only mice have fertility defects including reduced litter size and frequency. Follicles were counted in ovaries from 8.5- to 400-d-old females. Significantly fewer morphologically healthy antral follicles were found in 100- to 250-d FST288-only ovaries, but there were significantly more secondary, primary, and primordial follicles detected at d 8.5 in FST288-only ovaries. However, depletion of this primordial follicle pool is more rapid in FST288-only females resulting in a deficit by 250 d of age and early cessation of reproduction. Superovulated FST288-only females have fewer ovulated eggs and embryos. These results indicate that the FST isoforms have different activities in vivo, that the FST288-only isoform is sufficient for development, and that loss of FST303 and FST315 isoforms results in fertility defects that resemble activin hyperactivity and premature ovarian failure.

scholarly journals The effects of FSH and activin A on follicle development in vitro

Reproduction ◽  
2012 ◽  
Vol 143 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Davina A Cossigny ◽  
Jock K Findlay ◽  
Ann E Drummond
Keyword(s):  
Combined Treatment ◽  
Primordial Follicle ◽  
Treated Group ◽  
Activin A ◽  
Pcr Analysis ◽  
Follicle Development ◽  
Development In Vitro ◽  
Rates Of Growth

Numerous studies have reported on the roles of activins in gonadal regulation; however, little is known about their specific roles in early folliculogenesis. Ovarian follicular growth was investigated in 10-day cultures of day 4 postnatal whole ovaries treated with activin A (ActA; 50 ng/ml), with or without FSH (100 ng/ml) in vitro. We hypothesized that treatment with ActA±FSH would affect rates of growth and atresia in follicles. None of the treatments affected primordial follicle activation, and antral follicles were not observed after 10 days in culture. Primordial follicle numbers from all treatment groups were ∼20% of those in day 4 fresh ovaries, indicating that activation had occurred. In the presence of ActA, preantral follicle numbers increased significantly (P<0.0001). ActA alone decreased the proportion of atretic follicles in the primary and preantral classes, whereas the combined treatment of ActA+FSH increased the proportion of atretic preantral oocytes. Real-time PCR analysis revealed that follistatin, FSH receptor, and activin βA and βB subunits were all expressed at significantly higher levels in the ActA-only treated group but not in the ActA+FSH group. Here, we report novel findings supporting the role of FSH in primordial follicle survival through an action on apoptosis and a stimulatory role of ActA in the primordial to primary and preantral stages of follicle development, suggesting an inhibitory action of activin on oocyte apoptosis.

scholarly journals Regulation of Ovarian Primordial Follicle Assembly and Development by Estrogen and Progesterone: Endocrine Model of Follicle Assembly

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3329-3337 ◽  
Author(s):  
Phillip Kezele ◽  
Michael K. Skinner
Keyword(s):  
Granulosa Cells ◽  
Calf Serum ◽  
Single Layer ◽  
Primordial Follicle ◽  
Follicle Development ◽  
Newborn Rat ◽  
Primary Follicle ◽  
Primordial Follicles

Abstract The assembly of the developmentally arrested primordial follicle and the subsequent transition of the primordial follicle to the primary follicle are critical processes in normal ovarian physiology that remain to be elucidated. Ovarian follicles do not proliferate and the primordial follicles present in the neonate represent the total number of gametes available to a female throughout her reproductive life. The primordial follicles are oocytes surrounded by less differentiated squamous granulosa cells and are derived from oocyte nests, and primary follicles are oocytes surrounded by a single layer of cuboidal granulosa cells that have initiated follicle development. Abnormalities in primordial follicle assembly, arrest, and development (i.e. primordial to primary follicle transition) can cause pathological conditions such as premature ovarian failure. In this study newborn rat ovaries were cultured for 7 d. The rate of primordial follicle assembly in vivo was identical with the rate in vitro. Interestingly, the rate of primordial follicle transition to the primary follicle was found to be 3 times greater in culture. This abnormal rate of primary follicle development in culture suggests the primordial follicle does not arrest in development as observed in vivo. To investigate this phenomena newborn rat ovaries were cultured in the presence of progesterone, estradiol or calf serum. Estradiol, progesterone, or calf serum significantly reduced the level of initial primordial to primary follicle transition. Approximately 60% of follicles make the primordial to primary follicle transition in control ovaries and about 30% in treated ovaries. Steroids and calf serum had no effect on the primordial to primary follicle transition in ovaries collected and cultured from postnatal 4-d-old rats, suggesting the effects observed are restricted to the initial wave of primordial to primary follicle transition. Interestingly, progesterone was also found to significantly reduce the rate of primordial follicle assembly. All viable oocytes assembled into primordial follicles in control ovaries and approximately 40% remained unassembled in progesterone-treated ovaries. Progesterone was also found to reduce primordial follicle assembly in vivo with 10% of the total follicles remaining unassembled in progesterone injected neonatal animals. Analysis of cellular apoptosis demonstrated that progesterone inhibited the coordinated oocyte apoptosis required for primordial follicle assembly. The hypothesis developed is that high levels of maternal and fetal steroids prevent premature primordial follicle assembly and primordial to primary follicle transition in the embryo. After birth steroid levels fall dramatically and the primordial follicles are free to assemble and initiate development. These observations suggest a novel role for steroids and the maternal-fetal endocrine unit in the control of ovarian primordial follicle assembly and early follicular development.

scholarly journals Oocyte Survival and Development During Follicle Formation and Folliculogenesis in Mice Lacking Aromatase

2021 ◽  
Author(s):  
Jessica M. Toothaker ◽  
Kristen Roosa ◽  
Alexandra Voss ◽  
Suzanne M. Getman ◽  
Melissa Pepling
Keyword(s):  
Germ Cells ◽  
Ovarian Reserve ◽  
Primordial Germ Cells ◽  
Primordial Follicle ◽  
Follicle Development ◽  
Primordial Follicles ◽  
Survival And Development ◽  
Hemosiderin Deposits

Abstract BackgroundAssembly of oocytes into primordial follicles is essential for establishing the ovarian reserve required for female fertility. In mice, this process begins during embryonic development. Primordial germ cells form cysts by incomplete mitosis until 13.5 days post coitum (dpc). These cysts break down just before birth. Some oocytes undergo apoptosis while surviving oocytes are enclosed by granulosa cells to form primordial follicles. Cyst breakdown and primordial follicle formation were previously shown to be inhibited by estradiol and estrogenic compounds in vitro, suggesting that estrogen is important for regulation of this process. MethodsTo determine the role of fetal estrogen in cyst breakdown and follicle formation these processes were quantified in aromatase deficient (ArKO) mice between 17.5 dpc and postnatal day (PND) 9. Ovaries of ArKO mice were also examined at 2-week intervals to determine if folliculogenesis is affected by lack of estrogen and the age at which the typical ArKO ovarian phenotype first appears. ResultsOocyte number, follicle assembly and follicle development in ArKO mice did not differ from controls between 17.5 dpc and PND9 except for a difference in the proportion of follicles at the primordial and primary stage at PND7. At 2 weeks, ArKO heterozygous and homozygous ovaries still had oocytes in cyst while all oocytes were enclosed in follicles in wildtype ovaries. From 2 to 8 weeks oocyte numbers were similar in all genotypes though there was a trend toward fewer total oocytes in ArKO homozygous females as compared to controls at 8 weeks and a significant reduction at 10 weeks. Abnormal structures such as hemorrhagic follicles and hemosiderin deposits were also observed starting at 6 weeks. ConclusionsThese results suggest that a lack of fetal estrogen does not affect the rate of cyst breakdown or primordial follicle formation perinatally, and maternal estrogen or other signals are the chief regulators. Furthermore, the typical ArKO ovarian phenotype occurs earlier than previously reported.

scholarly journals Interleukin-8 Activates Breast Cancer-Associated Adipocytes and Promotes Their Angiogenesis- and Tumorigenesis-Promoting Effects

2018 ◽  
Vol 39 (2) ◽  
Author(s):  
Huda H. Al-Khalaf ◽  
Bothaina Al-Harbi ◽  
Adher Al-Sayed ◽  
Maria Arafah ◽  
Asma Tulbah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Critical Role ◽  
Ectopic Expression ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Therapeutic Value ◽  
Invasive Breast Carcinomas

ABSTRACT Increasing evidence supports the critical role of active stromal adipocytes in breast cancer development and spread. However, the mediators and the mechanisms of action are still elusive. We show here that cancer-associated adipocytes (CAAs) isolated from 10 invasive breast carcinomas are proinflammatory and exhibit active phenotypes, including higher proliferative, invasive, and migratory capacities compared to their adjacent tumor-counterpart adipocytes (TCAs). Furthermore, all CAAs secreted higher level of interleukin-8 (IL-8), which is critical in mediating the paracrine procarcinogenic effects of these cells. Importantly, ectopic expression of IL-8 in TCA cells activated them and enhanced their procarcinogenic effects both in vitro, in a STAT3-dependent manner, and in vivo. In contrast, inhibition of the IL-8 signaling using specific short hairpin RNA, anti-IL-8 antibody, or reparixin suppressed the active features of CAAs, including their non-cell-autonomous tumor-promoting activities both on breast luminal cells and in orthotopic tumor xenografts in mice. IL-8 played also an important role in enhancing the proangiogenic effects of breast adipocytes. These results provide clear indication that IL-8 plays key roles in the activation of breast CAAs and acts as a major mediator for their paracrine protumorigenic effects. Thus, targeting CAAs by inhibiting the IL-8 pathway could have great therapeutic value.

Proteoglycans decorin and biglycan differentially modulate TGF-β-mediated fibrotic responses in the lung

2001 ◽  
Vol 280 (6) ◽  
pp. L1327-L1334 ◽  
Author(s):  
Martin Kolb ◽  
Peter J. Margetts ◽  
Patricia J. Sime ◽  
Jack Gauldie
Keyword(s):  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Physiological Role ◽  
Tissue Response ◽  
Adenoviral Gene Transfer ◽  
Therapeutic Value ◽  
Fibrotic Disorders

Transforming growth factor (TGF)-β is a key cytokine in the pathogenesis of pulmonary fibrosis, and pharmacological interference with TGF-β can ameliorate the fibrotic tissue response. The small proteoglycans decorin and biglycan are able to bind and inhibit TGF-β activity in vitro. Although decorin has anti-TGF-β properties in vivo, little is known about the physiological role of biglycan in vivo. Adenoviral gene transfer was used to overexpress active TGF-β, decorin, and biglycan in cell culture and in murine lungs. Both proteoglycans were able to interfere with TGF-β bioactivity in vitro in a dose-dependant manner. In vivo, overexpression of TGF-β resulted in marked lung fibrosis, which was significantly reduced by concomitant overexpression of decorin. Biglycan, however, had no significant effect on lung fibrosis induced by TGF-β. The data suggest that differences in tissue distribution are responsible for the different effects on TGF-β bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung.

scholarly journals ERβ regulated ovarian kisspeptin plays an important role in oocyte maturation

2020 ◽  
Author(s):  
V. Praveen Chakravarthi ◽  
Subhra Ghosh ◽  
Katherine F. Roby ◽  
Michael W. Wolfe ◽  
M. A. Karim Rumi
Keyword(s):  
Estrogen Receptor ◽  
Oocyte Maturation ◽  
Essential Role ◽  
Follicle Development ◽  
Specific Expression ◽  
Gonadotropin Secretion ◽  
Antral Follicles ◽  
Intracellular Ca

AbstractKisspeptin (KISS1) signaling in the hypothalamic-pituitary (H-P) axis plays essential role in regulating gonadotropin secretion. KISS1 and KISS1 receptor (KISS1R) are also expressed in the ovary; however, the role of intraovarian KISS1 signaling remains largely unclear. Granulosa cell (GC)-specific expression of KISS1, and oocyte-specific expression of KISS1R indicate that GC-derived KISS1 may act on oocytes. Expression of KISS1 in GCs is induced by gonadotropins but it is absent in estrogen receptor β knockout (Erβnull) rats. We also observed that gonadotropin stimulation failed to induce maturation of Erβnull oocytes. Interestingly, KISS1 treatment of cumulus oocyte complexes (COCs) isolated from antral follicles promotes in vitro maturation of oocytes. Treatment of oocytes with KISS1 induced intracellular Ca2+ release, and increased activation of MAP kinase ERK1/2. KISS1 treatment also induced the expression of oocyte genes that are crucial for differentiation of GCs, and maturation of oocytes. Our findings suggest that ovarian KISS1-signaling plays an important role in gonadotropin induced follicle development and oocyte maturation.

scholarly journals Comparative Analysis Among Different Species Reveals That the Androgen Receptor Regulates Chicken Follicle Selection Through Species-Specific Genes Related to Follicle Development

2022 ◽  
Vol 12 ◽  
Author(s):  
Ying Huang ◽  
Wei Luo ◽  
Xuliang Luo ◽  
Xiaohui Wu ◽  
Jinqiu Li ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Granulosa Cells ◽  
Egg Production ◽  
Androgen Receptors ◽  
Follicular Development ◽  
Follicle Development ◽  
Follicle Selection

The differences in reproductive processes at the molecular level between viviparous and oviparous animals are evident, and the site in the ovary that synthesizes sex hormones (androgens and oestrogens) and the trends for enriching sex hormones during follicle development in chickens are different from those in mammals, suggesting that the effect of sex hormones on follicle development in chickens is probably different from that in viviparous animals. To explore the specific role of androgen receptors (ARs) on chicken follicular development, we matched the correspondence of follicular development stages among chickens, humans, cows and identified chicken-specific genes related to follicle development (GAL-SPGs) by comparing follicle development-related genes and their biological functions among species (chickens, humans, and cows). A comparison of the core transcription factor regulatory network of granulosa cells (or ovaries) based on super-enhancers among species (chicken, human, and mouse) revealed that AR is a core transcriptional regulator specific to chickens. In vivo experiments showed that inhibition of AR significantly reduced the number of syf (selected stage follicles) in chickens and decreased the expression of GAL-SPGs in F5 follicles, while in vitro experiments showed that inhibition of AR expression in chicken granulosa cells (GCs) significantly down-regulated the expression levels of GAL-SPGs, indicating that AR could regulate follicle selection through chicken-specific genes related to follicle development. A comparison among species (77 vertebrates) of the conserved genomic regions, where chicken super-enhancers are located, revealed that the chicken AR super-enhancer region is conserved in birds, suggesting that the role of AR in follicle selection maybe widespread in birds. In summary, we found that AR can regulate follicle selection through chicken-specific genes related to follicle development, which also emphasizes the important role of AR in follicle selection in chickens and provides a new perspective for understanding the unique process of follicle development in chickens. Our study will contribute to the application of androgens to the control of egg production in chickens and suggests that researchers can delve into the mechanisms of follicle development in birds based on androgen/androgen receptors.

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