scholarly journals Nitric oxide in follicle development and oocyte competence

Reproduction ◽  
2015 ◽  
Vol 150 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Giuseppina Basini ◽  
Francesca Grasselli

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.

2018 ◽  
Author(s):  
Sarai Pacheco ◽  
Montserrat Garcia-Caldés ◽  
Ignasi Roig

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.


2018 ◽  
Vol 44 (1) ◽  
pp. 15
Author(s):  
Livia Brunetti Apolloni ◽  
Jamily Bezerra Bruno ◽  
Benner Geraldo Alves ◽  
José Ricardo de Figueiredo

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.


Endocrinology ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1166-1174 ◽  
Author(s):  
Olga Astapova ◽  
Briaunna M N Minor ◽  
Stephen R Hammes

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.


2021 ◽  
Vol 69 (1) ◽  
pp. 39-48
Author(s):  
Jiaran Zhu ◽  
Shenqiang Hu ◽  
Yao Lu ◽  
Yujing Rong ◽  
Enhua Qing ◽  
...  

Cathepsin D (CTSD) is known to be crucial for the degradation and utilization of yolk precursors in ovarian follicles. However, little is known about its expression profiles and physiological actions in avian ovarian cells. In this study, the intact coding sequence of the CTSD gene in geese was cloned for the first time, with a length of 1197 bp. It encoded a polypeptide of 398 amino acids (AA) consisting of a signal peptide and two conserved functional domains (i.e., A1_Propeptide and Cathepsin_D2). The AA sequence of goose CTSD had > 96% similarities with the homologs of turkeys, chickens, and ducks. Results from real-time PCR showed that goose CTSD mRNA was present in all tissues examined, with higher levels in the adrenal gland, liver, heart, and reproductive organs. Furthermore, levels of CTSD mRNA were much higher in goose granulosa layers than in the theca layers in any follicular category. Significantly, its expression remained almost unchanged in the theca layers throughout follicle development, while it increased gradually in the granulosa layers from 2-4 mm to F5 follicles but declined there after. These results suggested that CTSD may regulate goose ovarian follicle development through its actions on both the degradation and absorption of yolk precursors and granulosa cell apoptosis.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Luju Lai ◽  
Xiaoyun Shen ◽  
Haoqin Liang ◽  
Yingying Deng ◽  
Zhuandi Gong ◽  
...  

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.


2008 ◽  
Vol 199 (2) ◽  
pp. 307-316 ◽  
Author(s):  
V Tripathi ◽  
A Krishna

The purpose of the study was to demonstrate the presence of nitric oxide (NO) synthase (NOS) isoforms (neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS)) and the role of NO in the ovary of Heteropneustes fossilis. In one half of the ovary collected during different reproductive stages, NOS isoforms were localized immunohistochemically in paraffin sections whereas the other half was processed for NOS and NO quantification using western blot followed by densitometry and nitrate/nitrite assay respectively. The role of NO on oocyte maturation was studied by examining the effect of NO donor (sodium nitroprusside; SNP) and NOS inhibitor (Nω-nitro-l-arginine methyl ester) on 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-P)-induced germinal vesicle breakdown (GVBD) in the cultured oocyte collected during prespawning phase. NOS immunostaining was predominantly localized in previtellogenic follicles, with nNOS detected in the nucleus and cytoplasm of oocytes whereas iNOS and eNOS localized in granulosa, theca cells, and cytoplasm of oocytes. The NOS expression was higher in previtellogenic phase when compared with vitellogenic phase. The nitrate/nitrite concentrations in ovary showed gradual increase from recrudescence (4.9±0.19 nM/mg protein) to late previtellogenic phase (7.02±0.53 nM/mg protein), but showed a sharp decline during the vitellogenic phase (0.41±0.053 nM/mg protein). Serum and ovarian nitrate/nitrite level showed a close association during the reproductive cycle. The results showed an increase in NOS activity and nitrate/nitrite concentrations as the follicle grow suggesting involvement of NO in follicular development. SNP significantly inhibited 17α,20β-P-induced GVBD in fish oocytes. Thus, it is concluded that the fish ovary possesses NOS/NO system and a possibility that NO has a role in follicular development and regulation of oocyte maturation in fish, H. fossilis.


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 ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Liyuan Li ◽  
Xiaojin Shi ◽  
Yun Shi ◽  
Zhao Wang

The follicle is the functional unit of the ovary, which is composed of three types of cells: oocytes, granulosa cells, and theca cells. Ovarian follicle development and the subsequent ovulation process are coordinated by highly complex interplay between endocrine, paracrine, and autocrine signals, which coordinate steroidogenesis and gametogenesis. Follicle development is regulated mainly by three organs, the hypothalamus, anterior pituitary, and gonad, which make up the hypothalamic-pituitary-gonadal axis. Steroid hormones and their receptors play pivotal roles in follicle development and participate in a series of classical signaling pathways. In this review, we summarize and compare the role of classical signaling pathways, such as the WNT, insulin, Notch, and Hedgehog pathways, in ovarian follicle development and the underlying regulatory mechanism. We have also found that these four signaling pathways all interact with FOXO3, a transcription factor that is widely known to be under control of the PI3K/AKT signaling pathway and has been implicated as a major signaling pathway in the regulation of dormancy and initial follicular activation in the ovary. Although some of these interactions with FOXO3 have not been verified in ovarian follicle cells, there is a high possibility that FOXO3 plays a core role in follicular development and is regulated by classical signaling pathways. In this review, we present these signaling pathways from a comprehensive perspective to obtain a better understanding of the follicular development process.


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