scholarly journals ATR function is indispensable to allow proper mammalian follicle development

2018 ◽  
Author(s):  
Sarai Pacheco ◽  
Montserrat Garcia-Caldés ◽  
Ignasi Roig
Keyword(s):  
Follicular Development ◽  
Female Fertility ◽  
Follicle Development ◽  
Wild Type ◽  
Hypomorphic Mutation ◽  
Ovarian Cells ◽  
Anti Cancer ◽  
Mammalian Female ◽  
Atr Kinase

AbstractMammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.

scholarly journals Nitric oxide in follicle development and oocyte competence

Reproduction ◽  
2015 ◽  
Vol 150 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Giuseppina Basini ◽  
Francesca Grasselli
Keyword(s):  
Nitric Oxide ◽  
Follicular Development ◽  
Reproductive Organs ◽  
Follicle Development ◽  
Oocyte Competence ◽  
Positive Effects ◽  
Ovarian Cells ◽  
Dual Action ◽  
Generating System

Apart from its well-known role in regulating endothelial function, in mammals, nitric oxide (NO) is an important signaling molecule involved in many processes, regulating different biological functions. It has been demonstrated that NO plays a role in the physiology of the reproductive system, where it acts in controlling the activity of reproductive organs in both sexes. In the female of several animal species, experimental data suggest the presence of an intraovarian NO-generating system, which could be involved in the control of follicular development. The role of NO in regulating follicular atresia by apoptosis is still controversial, as a dual action depending mostly on its concentration has been documented. NO also displays positive effects on follicle development and selection related to angiogenic events and it could also play a modulatory role in steroidogenesis in ovarian cells. Both in monovulatory and poliovulatory species, the increase in PGE2production induced by NO via a stimulatory effect on COX-2 activity appears to be a common ovulatory mechanism. Considerable evidence also exists to support an involvement of the NO/NO synthase system in the control of meiotic maturation of cumulus–oocyte complexes.

scholarly journals The Role of Androgens in Mammals Folliculogenesis

2018 ◽  
Vol 44 (1) ◽  
pp. 15
Author(s):  
Livia Brunetti Apolloni ◽  
Jamily Bezerra Bruno ◽  
Benner Geraldo Alves ◽  
José Ricardo de Figueiredo
Keyword(s):  
Androgen Receptor ◽  
In Vitro Culture ◽  
Steroid Hormones ◽  
Oocyte Maturation ◽  
Follicular Development ◽  
Follicular Growth ◽  
Preantral Follicles ◽  
Ovarian Cells

Introduction: Steroid hormones production is a physiological process termed steroidogenesis. An important stage of this process is the conversion of androgens into estrogens through aromatase enzyme. Furthermore, androgens are important in the process of folliculogenesis, promoting follicular growth in different species. Thus, the aim of this review was to present the process of synthesis, mechanism of action, and importance of androgens in folliculogenesis. Additionally, the main results of in vitro culture of ovarian cells in the presence of these hormones were emphasized.Review: Folliculogenesis begins in prenatal life in most of species and can be defined as the process of formation, follicular growth, and oocyte maturation. Preantral follicles represent 95% of the follicular population and assisted reproductive technologies have been developed (e.g., Manipulation of Oocytes Enclosed in Preantral Follicles - MOEPF) in order to avoid the great follicle loss that occurs naturally in vivo by atresia. The MOEPF aim to obtain a large number of competent oocytes from preantral follicles and then subject to in vitro maturation, fertilization, and culture for embryo production. However, the development of an efficient medium to ensure the follicular survival and oocyte maturation is the major challenge of this biotechnology. To achieve the success on in vitro culture, the effects of substances as androgens on follicular development have been evaluated. Androgens are steroid hormones produced in theca cells (TC) that are fundamental for follicular growth. These cells provide all the androgens required by the developing follicles for conversion into estrogens by the granulosa cells (GC). Androgens receptors (AR) are localized in cell cytoplasm of all follicular categories, being more expressed in preantral follicles. The androgen pathway initiates through its connection to its receptor, making a complex androgen-AR, that in the nucleus helps on the process of gene transcription related with follicular survival. This mechanism is androgen receptor genomic activity. In addition to genomic action, there is an androgen receptor non-genomic activity. This occurs through activation of AR and its interaction with different signaling molecules located on the cell membrane, triggering events that aid in the follicular development. Regardless of the androgens actions, ovarian cells of several species subjected to in vitro culture have shown the importance of these hormones on the follicle development. Recent studies demonstrated that androgens addition on the culture medium stimulated the activation of preantral follicles (bovine and caprine), antrum formation (swine), survival (non-primate), and oocyte maturation (antral follicles; bovine). Also, some studies suggest that the addition of these hormones on in vitro culture is dose-dependent and species-specific.Conclusion: This review shows the role of androgens in different stages of follicular development and its action as a substrate for steroidogenesis and transcription of genes related to follicular survival and oocyte maturation. However, when these hormones should be added during in vitro follicular culture and which concentration is required remains unclear, being necessary more studies to elucidate these aspects.

scholarly journals Salt-inducible Kinases Are Critical Determinants of Female Fertility

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Marah Armouti ◽  
Nicola Winston ◽  
Osamu Hatano ◽  
Elie Hobeika ◽  
Jennifer Hirshfeld-Cytron ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Follicle Stimulating Hormone ◽  
Female Fertility ◽  
Camp Signaling ◽  
Follicle Development ◽  
Pharmacological Modulation ◽  
Ovarian Granulosa Cells ◽  
Different Levels

Abstract Follicle development is the most crucial step toward female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein kinase A by increasing 3′,5′-cyclic adenosine 5′-monophosphate (cAMP). Since cAMP signaling is impinged in part by salt-inducible kinases (SIKs), we examined the role of SIKs on the regulation of FSH actions. Here, we report that SIKs are essential for normal ovarian function and female fertility. All SIK isoforms are expressed in human and rodent GCs at different levels (SIK3>SIK2>SIK1). Pharmacological inhibition of SIK activity potentiated the stimulatory effect of FSH on markers of GC differentiation in mouse, rat, and human GCs and estradiol production in rat GCs. In humans, SIK inhibition strongly enhanced FSH actions in GCs of patients with normal or abnormal ovarian function. The knockdown of SIK2, but not SIK1 or SIK3, synergized with FSH on the induction of markers of GC differentiation. SIK inhibition boosted gonadotropin-induced GC differentiation in vivo, while the genomic knockout of SIK2 led to a significant increase in the number of ovulated oocytes. Conversely, SIK3 knockout females were infertile, FSH insensitive, and had abnormal folliculogenesis. These findings reveal novel roles for SIKs in the regulation of GC differentiation and female fertility, and contribute to our understanding of the mechanisms regulated by FSH. Furthermore, these data suggest that specific pharmacological modulation of SIK2 activity could be of benefit to treat ovulatory defects in humans and to increase the propagation of endangered species and farm mammals.

Efficient generation of bone morphogenetic protein 15-edited Yorkshire pigs using CRISPR/Cas9†

2020 ◽  
Vol 103 (5) ◽  
pp. 1054-1068
Author(s):  
Xuan Shi ◽  
Tao Tang ◽  
Qiyuan Lin ◽  
Hongbo Liu ◽  
Yufeng Qin ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Follicular Development ◽  
Female Fertility ◽  
Efficient Generation ◽  
Morphogenetic Protein ◽  
Yorkshire Pigs ◽  
Bone Morphogenetic Protein 15 ◽  
Ovarian Follicular Development

Abstract Bone morphogenetic protein 15 (BMP15), a member of the transforming growth factor beta superfamily, plays an essential role in ovarian follicular development in mono-ovulatory mammalian species. Studies using a biallelic knockout mouse model revealed that BMP15 potentially has just a minimal impact on female fertility and ovarian follicular development in polyovulatory species. In contrast, our previous study demonstrated that in vivo knockdown of BMP15 significantly affected porcine female fertility, as evidenced by the dysplastic ovaries containing significantly decreased numbers of follicles and an increased number of abnormal follicles. This finding implied that BMP15 plays an important role in the regulation of female fertility and ovarian follicular development in polyovulatory species. To further investigate the regulatory role of BMP15 in porcine ovarian and follicular development, here, we describe the efficient generation of BMP15-edited Yorkshire pigs using CRISPR/Cas9. Using artificial insemination experiments, we found that the biallelically edited gilts were all infertile, regardless of different genotypes. One monoallelically edited gilt #4 (Δ66 bp/WT) was fertile and could deliver offspring with a litter size comparable to that of wild-type gilts. Further analysis established that the infertility of biallelically edited gilts was caused by the arrest of follicular development at preantral stages, with formation of numerous structurally abnormal follicles, resulting in streaky ovaries and the absence of obvious estrous cycles. Our results strongly suggest that the role of BMP15 in nonrodent polyovulatory species may be as important as that in mono-ovulatory species.

scholarly journals Physiological and Pathological Androgen Actions in the Ovary

Endocrinology ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1166-1174 ◽  
Author(s):  
Olga Astapova ◽  
Briaunna M N Minor ◽  
Stephen R Hammes
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Follicle Development ◽  
Female Reproduction ◽  
Negative Effects ◽  
Androgen Excess ◽  
Male Sex ◽  
Androgen Effects

Abstract Androgens, although traditionally thought to be male sex steroids, play important roles in female reproduction, both in healthy and pathological states. This mini-review focuses on recent advances in our knowledge of the role of androgens in the ovary. Androgen receptor (AR) is expressed in oocytes, granulosa cells, and theca cells, and is temporally regulated during follicular development. Mouse knockout studies have shown that AR expression in granulosa cells is critical for normal follicular development and subsequent ovulation. In addition, androgens are involved in regulating dynamic changes in ovarian steroidogenesis that are critical for normal cycling. Androgen effects on follicle development have been incorporated into clinical practice in women with diminished ovarian reserve, albeit with limited success in available literature. At the other extreme, androgen excess leads to disordered follicle development and anovulatory infertility known as polycystic ovary syndrome (PCOS), with studies suggesting that theca cell AR may mediate many of these negative effects. Finally, both prenatal and postnatal animal models of androgen excess have been developed and are being used to study the pathophysiology of PCOS both within the ovary and with regard to overall metabolic health. Taken together, current scientific consensus is that a careful balance of androgen activity in the ovary is necessary for reproductive health in women.

Potential role of microRNAs in mammalian female fertility

2017 ◽  
Vol 29 (1) ◽  
pp. 8 ◽  
Author(s):  
Dawit Tesfaye ◽  
Dessie Salilew-Wondim ◽  
Samuel Gebremedhn ◽  
Md Mahmodul Hasan Sohel ◽  
Hari Om Pandey ◽  
...  
Keyword(s):  
Embryo Development ◽  
Oocyte Maturation ◽  
Potential Role ◽  
Mammalian Species ◽  
Female Fertility ◽  
Conditional Knockout ◽  
Female Reproduction ◽  
Extracellular Mirnas ◽  
Mammalian Female

Since the first evidence for the involvement of microRNAs (miRNAs) in various reproductive processes through conditional knockout of DICER, several studies have been conducted to investigate the expression pattern and role of miRNAs in ovarian follicular development, oocyte maturation, embryo development, embryo–maternal communication, pregnancy establishment and various reproductive diseases. Although advances in sequencing technology have fuelled miRNA studies in mammalian species, the presence of extracellular miRNAs in various biological fluids, including follicular fluid, blood plasma, urine and milk among others, has opened a new door in miRNA research for their use as diagnostic markers. This review presents data related to the identification and expression analysis of cellular miRNA in mammalian female fertility associated with ovarian folliculogenesis, oocyte maturation, preimplantation embryo development and embryo implantation. In addition, the relevance of miRNAs to female reproductive disorders, including polycystic ovary syndrome (PCOS), endometritis and abnormal pregnancies, is discussed for various mammalian species. Most importantly, the mechanism of release and the role of extracellular miRNAs in cell–cell communication and their potential role as non-invasive markers in female fertility are discussed in detail. Understanding this layer of regulation in female reproduction processes will pave the way to understanding the genetic regulation of female fertility in mammalian species.

Role of activin C in normal ovaries and granulosa cell tumours of mice and humans

2018 ◽  
Vol 30 (7) ◽  
pp. 958 ◽  
Author(s):  
Karen L. Reader ◽  
Francesco E. Marino ◽  
Helen D. Nicholson ◽  
Gail P. Risbridger ◽  
Elspeth J. Gold
Keyword(s):  
Granulosa Cell ◽  
Early Stage ◽  
Follicular Development ◽  
Surface Epithelium ◽  
Wild Type ◽  
Thecal Cells ◽  
Human Ovaries ◽  
Granulosa Cell Tumours ◽  
And Function

Activins and inhibins play important roles in the development, growth and function of the ovary. Mice lacking inhibin develop granulosa cell tumours in their ovaries that secrete activin A, and these tumours are modulated by increased activin C expression. The aim of the present study was to identify where activin C is expressed in mouse and human ovaries and whether overexpression of activin C modulates normal follicular development in mice. Immunohistochemical staining for the activin βC subunit was performed on sections from mouse and human ovaries and human adult granulosa cell tumours. Stereology techniques were used to quantify oocyte and follicular diameters, and the percentage of different follicular types in ovaries from wild-type mice and those underexpressing inhibin α and/or overexpressing activin C. Staining for activin βC was observed in the oocytes, granulosa cells, thecal cells and surface epithelium of mouse and human ovaries, and in the granulosa-like cells of adult granulosa cell tumours. Overexpression of activin C in mice did not alter follicular development compared with wild-type mice, but it did modulate the development of abnormal early stage follicles in inhibin α-null mice. These results provide further evidence of a role for activin C in the ovary.

scholarly journals Determine the Role of FSH Receptor Binding Inhibitor in Regulating Ovarian Follicles Development and Expression of FSHR and ERα in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Luju Lai ◽  
Xiaoyun Shen ◽  
Haoqin Liang ◽  
Yingying Deng ◽  
Zhuandi Gong ◽  
...  
Keyword(s):  
Follicular Development ◽  
Transverse Diameter ◽  
Follicle Development ◽  
Fsh Receptor ◽  
Serum Concentrations ◽  
Primordial Follicles ◽  
Protein Levels ◽  
Ovarian Cortex ◽  
Longitudinal Diameter

Mice of FRBI-1, FRBI-2, and FRBI-3 groups were intramuscularly injected with 20, 30, and 40mg/kg, respectively, for five consecutive days. Ovarian weights of three FRBI groups were reduced in comparison with FSH group. Ovarian cortex thicknesses (OCT) of the FRBI-3 group were less than that of the FSH group (P<0.05). As compared to FSH group, there were fewer numbers of secondary follicles (SFs) and mature follicles (MF) on the ovaries of FRBI-treated mice numbers of primary follicles (PFs) and SFs also decreased. In FRBI-3 mice, we found that the primordial follicles (POF) were scarcer, the follicles developed poorly, and granulosa cells became apoptosis. SF numbers of FRBI-2 and FRBI-3 groups were less than that of the FSH group on day 20 (P<0.05). Maximum longitudinal diameter (MLD) and transverse diameter (MTD) of three FRBI groups became decreased during the experiment. MLD and MTD of the FRBI-3 group were smaller than FSH group. Levels of FSHR mRNA and protein were less than that of CG and FSH group (P<0.05). ERα protein levels of FRBI group and serum concentrations of FSH and estradiol (E2) in the FRBI-treated mice were decreased when compared to CG and FSH group. In conclusion, FSH treatment could increase the numbers of SF and MF, enhance follicle development, reduce the numbers of SF and MF, and depress the follicular development of mice. Furthermore, FRBI declined the mRNA and protein levels of ERα and FSHR in the ovaries and dropped serum concentrations of FSH and E2 of mice.

scholarly journals Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

2019 ◽  
Author(s):  
Yufeng Qin ◽  
Tao Tang ◽  
Wei Li ◽  
Zhiguo Liu ◽  
Xiaoliang Yang ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Essential Role ◽  
Mammalian Species ◽  
Critical Role ◽  
Follicular Development ◽  
Female Fertility ◽  
Regulatory Function ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

ABSTRACTBone morphogenetic protein 15 (BMP15) is a multifunctional oocyte-specific secreted factor. It controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role on follicular development and ovulation rate of mono-ovulatory mammalian species, but has minimal impact on poly-ovulatory mice. However, whether this is true in non-rodent poly-ovulatory species need to be validated. To investigate this question, we generated a BMP15 knockdown pig model. We found that BMP15 knockdown gilts showed markedly reduced fertility accompanied with phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation. Molecular and transcriptome analysis revealed that knockdown of BMP15 significantly suppressed cell proliferation, differentiation, Fshr expression, leading to premature luteinization and reduced estradiol production in GCs, and simultaneously decreased the quality and meiotic maturation of oocyte. Our results provide in vivo evidences for the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.

Role of nerve growth factor (NGF) and its receptors in folliculogenesis

Zygote ◽  
2012 ◽  
Vol 21 (2) ◽  
pp. 187-197 ◽  
Author(s):  
R.N. Chaves ◽  
A.M.C.V. Alves ◽  
L.F. Lima ◽  
H.M.T. Matos ◽  
A.P.R. Rodrigues ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Nerve Growth ◽  
Ovarian Follicle Development ◽  
Ovarian Cells ◽  
Affinity Receptor

SummaryNerve growth factor (NGF) is a prototype member of the neurotrophins family and has important functions in the maintenance of viability and proliferation of neuronal and non-neuronal cells, such as certain ovarian cells. The present review highlights the role of NGF and its receptors on ovarian follicle development. NGF initiates its multiple actions through binding to two classes of receptors: the high affinity receptor tyrosine kinase A (TrkA) and the low-affinity receptor p75. Different intracytoplasmic signalling pathways may be activated through binding to NGF due to variation in the receptors. The TrkA receptor activates predominantly phosphatidylinositol-3-kinase (PI3K) and mitogenic activated protein kinase (MAPK) to promote cell survival and proliferation. The activation of the phospholipase type Cγ (PLCγ) pathway, which results in the production of diacylglycerol (DAG) and inositol triphosphate (IP3), culminates in the release of calcium from the intracytoplasmic cellular stocks. However, the details of activation through p75 receptor are less well known. Expression of NGF and its receptors is localized in ovarian cells (oocyte, granulosa, theca and interstitial cells) from several species, which suggests that NGF and its receptors may regulate some ovarian functions such as follicular survival or development. Thus, the use of NGF in culture medium for ovarian follicles may be of critical importance for researchers who want to promote follicular developmentin vitroin the future.

Sign in / Sign up

Export Citation Format

Share Document