DOCSLIB.ORG

Downloaded from Bioscientifica.Com at 09/29/2021 03:21:28PM Via Free Access 434 O

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Downloaded from Bioscientifica.Com at 09/29/2021 03:21:28PM Via Free Access 434 O Journal of Reproduction and Fertility (2000) 120, 433–442 Effect of TNF-α on LH and IGF-I modulated chicken granulosa cell proliferation and progesterone production during follicular development O. M. Onagbesan*, J. Mast, B. Goddeeris and E. Decuypere Laboratory for Physiology and Immunology of Domestic Animals, Catholic University of Leuven, Kardinaal Mercierlaan 92, B-3001 Heverlee, Belgium This study demonstrates the effects of recombinant human tumour necrosis factor α (rhTNF-α) and conditioned medium of the HD11-transformed chicken macrophage cell line on cultured chicken granulosa cells. Effects were studied on basal, IGF-I- and LH-stimulated progesterone production and cell proliferation. Recombinant human TNF-α stimulated basal progesterone production in a dose-dependent manner in the granulosa cells of the largest follicle but had no effect on cells from the third largest follicle. TNF-α stimulated and sometimes inhibited progesterone production stimu- lated by IGF-I and LH alone or in combination depending on the size of the follicle and the concentration of LH or IGF-I applied. However, the inhibitory effect of TNF-α was significantly more pronounced in cells from the third largest follicle when high concentrations of IGF-I, LH or a combination of both were applied. TNF-α had no effect on basal cell proliferation in both the largest and the third largest follicles, but regulated responses to IGF-I and a combination IGF-I and LH in the cells of the third largest follicle but not those of the largest follicle. The data indicate that the normal hierarchy of follicles is maintained in the chicken ovary through the regulation of the activity of IGF- I and its interaction with LH. Conditioned medium of LPS-activated HD11 macro- phages mimicked the effects of TNF-α and its interaction with IGF-I and LH on progesterone production and cell proliferation. The observation that the HD11- conditioned medium contained TNF-α indicates that TNF-α produced by macrophages found in chicken follicles modulates granulosa cell growth and differentiation. Introduction inhibits IGF-I- or LH-stimulated androgen production (Andreani et al., 1991; Zachow et al., 1993; Zachow and Tumour necrosis factor α (TNF-α) is a 17 kDa protein Terranova, 1994; Acosta et al., 1998). TNF-α stimulates prolif- produced by both mammalian and avian macrophages when eration of human luteal cells, but induces apoptosis in activated with lipopolysaccharides (LPS). This protein and granulosa cells of early antral follicles of rats (Wang et al., its mRNA have also been localized in ovarian granulosa, 1992; Yan et al., 1993; Kaipia et al., 1996). Spaczynski et al. theca and luteal cells of several mammalian species (Roby (1999) reported a stimulatory effect of TNF-α on basal and et al., 1990; Wuttke et al., 1993; Kondo et al., 1995; Terranova IGF-I- and FSH-stimulated proliferation of cultured theca et al., 1995; Shaw and Britt, 1995). Evidence indicates that interstitial cells of rats injected with oestradiol, whereas although ovarian cells are a source of TNF-α in the ovary, Andreani et al. (1991) and Zachow and Terranova (1993) local macrophages are the principal source (Bagavandoss found no effect on theca interstitial cells of hypophysec- et al., 1988; Adashi, 1990; Wang et al., 1992; Zhao et al., 1998). tomized rats. These findings indicate that TNF-α exerts a Several studies have shown that TNF-α has a role in wide variety of effects depending on the type of cell, stage of mammalian ovarian follicular development, steroidogenesis, development and the physiological environment. ovulation, luteolysis and atresia. In bovine, human and rat To date, the production of TNF-α and other cytokines in granulosa cells, TNF-α inhibits IGF-I- or gonadotrophin- follicular cells of the avian ovary has not been investigated. stimulated oestrogen production but either increases or Barua et al. (1998a,b) demonstrated the presence of macro- inhibits progesterone production depending on the stage of phages within the theca but not within the granulosa layers development of the follicle (Roby and Terranova, 1988; of chicken ovarian follicles. The macrophage population in Montgomery Rice et al., 1998, 1999; Spicer, 1998). TNF-α also these follicles changes with maturation and the age of the *Correspondence address: IRS, University of Wales Aberystwyth SY23 3AL. bird, thus indicating a functional relevance of these macro- Received 10 January 2000. phages in the chicken ovary. The macrophages may be a © 2000 Journals of Reproduction and Fertility Ltd 0022–4251/2000 Downloaded from Bioscientifica.com at 09/29/2021 03:21:28PM via free access 434 O. M. Onagbesan et al. source of TNF-α and other cytokines that influence follicular 30 functions. There are indications that TNF-α may influence chicken follicular growth and atresia. Recombinant human a 25 a a TNF-α (rhTNF-α) induces apoptosis in the granulosa cells of large white follicles and has a role in follicular atresia (Witty et al., 1996). TNF-α increased intracellular calcium in ) 20 a –1 granulosa cells of chickens without a concomitant increase in a progesterone production (Soboloff et al., 1995, 1999). Bryan et 15 α –1 (pg ml al. (1997) showed that 5 ng TNF- ml had an inhibitory α effect on progesterone production by granulosa cells of two lines of chicken, whereas 250 ng ml–1 had either no effect or TNF- 10 was stimulatory. These studies were conducted under acute b conditions of 3 h incubations, which may have been 5 responsible for the inconsistent results. There are no reports on the effect of TNF-α on chicken granulosa or theca 0 cell proliferation, or its effects on gonadotrophin-or IGF-I- 0 1.25 2.5 5 10 20 stimulated progesterone production or cell proliferation in LPS (lg ml–1) cultured cells. The aim of the current study was to investi- Fig. 1. TNF-α content of medium conditioned with HD11 macro- gate the response of cultured granulosa cells of the largest phage cell line activated with increasing doses of lipopolysaccharide α and third largest follicles to rhTNF- treatment in the (LPS). Cells were cultured for 72 h in Dulbecco’s modified Eagle’s presence or absence of LH and IGF-I. Since chicken medium (DMEM) supplemented with 5% heat-activated chicken macrophages present in the follicles are a potential source of serum. Data points represent means Ϯ SEM of determinations in TNF-α for autocrine or paracrine regulation of granulosa and medium collected from four separate experiments. Data were theca cell functions, granulosa cells were treated with analysed by ANOVA and differences compared by Duncan’s conditioned media generated from macrophages activated multiple-range test. Significant differences between means are with or without LPS. Progesterone production was quantified denoted by different letters (P < 0.05). in culture medium and the effects on cell proliferation during culture were determined. LPS was subsequently used for generating macrophage- conditioned medium designated as MCMWLPS. Conditioned medium generated from HD11 cell cultures without LPS was designated as MCMWOLPS. Materials and Methods Preparation of conditioned medium from the HD11 chicken macrophage cell line Chicken granulosa cell preparation and culture The avian leukaemia virus (strain MC29) transformed Laying ISA Brown hens of 35–45 weeks of age were kept in chicken macrophage cell line HD11 (Beug et al., 1979) was cages under a photoperiod of 14 h light:10 h dark. Chickens used for preparing conditioned medium. The HD11 cells were provided with food and water ad libitum and laying were cultured in Dulbecco’s modified Eagle’s medium was monitored each day. Hens were killed by cervical (DMEM) (Sigma, Poole) supplemented with 5% heat- dislocation 12–16 h after an oviposition. The largest and third inactivated chicken serum, 2 mmol glutamine l–1, 1 mmol largest follicles were excised from the ovary and placed into sodium pyruvate l–1 (Sigma, Poole) and 0.1% (v/v) warmed (37ЊC) phenol red-free Hank’s balanced salt solution gentamycine (Gibco BRL, Paisley). The cells were seeded at (pfHBSS) (Gibco BRL, Paisley). The granulosa cell layer of 5 ϫ 106 in 72 cm2 200 ml cell culture flasks and incubated at the follicles was dissected out as described by Gilbert et al. 2+ 2+ 37ЊC in a humidified atmosphere of 5% CO2 for 72 h when 1977, and dispersed in Ca - and Mg -free Hank’s (Sigma) cells were just near-confluent. During the culture period, containing 0.1 mg collagenase ml–1 (Sigma) as described by cells were either treated without or with different Peddie et al. (1994). Cells from follicles of a similar size were concentrations of LPS (1.25–20.0 µg ml–1) (Sigma) to activate pooled from three to four hens and the cell density was TNF-α secretion into the culture medium. At the end of the determined by measuring the DNA in aliquots using the culture period, medium was collected, sterilized by filtration method of Labarca and Paigen (1980) in which 1 µg DNA = through 0.22 µm sterile filters (Gelman) and stored at –20ЊC 105 cells. Cell viability was assessed using the trypan blue until used. Activation of the HD11 cells was later assessed by method and was usually > 90%. Cells were resuspended in measuring chicken TNF-α in the medium using a commer- Medium 199 (M199) (Gibco BRL, Paisley) supplemented cial ELISA kit for human TNF-α (Eurogenetics, Tessenderlo). with 2 mmol glutamine l–1, 40 mmol sodium bicarbonate l–1, The monoclonal antibody in this kit crossreacts with chicken 1% (v/v) PSA (antibiotic–antimycotic solution) (Sigma, TNF-α as determined by immunohistochemistry (data not Poole) and 5% charcoal-stripped fetal bovine serum (FBS) shown). The stimulatory effect of LPS on chicken TNF-α (Gibco BRL, Paisley) and plated at 0.1 ϫ 105 viable cells per production in the medium by the HD11 cells is shown (Fig.
Load more

Recommended publications
  • Effect of Insulin-Like Growth Factor-1 (IGF-1) on the Expression of Nfκb and Cflip in Bovine Granulosa Cells
    University of New Hampshire University of New Hampshire Scholars' Repository Student Research Projects Student Scholarship Spring 2014 Effect of Insulin-Like Growth Factor-1 (IGF-1) on the expression of NFκB and cFLIP in Bovine Granulosa Cells Samantha Kathleen Docos University of New Hampshire - Main Campus Follow this and additional works at: https://scholars.unh.edu/student_research Part of the Agriculture Commons, Animal Sciences Commons, Cellular and Molecular Physiology Commons, and the Endocrinology Commons Recommended Citation Docos, Samantha Kathleen, "Effect of Insulin-Like Growth Factor-1 (IGF-1) on the expression of NFκB and cFLIP in Bovine Granulosa Cells" (2014). Student Research Projects. 12. https://scholars.unh.edu/student_research/12 This Undergraduate Research Project is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Student Research Projects by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. Effect of Insulin-Like Growth Factor-1 (IGF-1) on the expression of NFκB and cFLIP in Bovine Granulosa Cells Samantha K. Docos, David H. Townson Dept. of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, 03824 Abstract Materials and Methods Results Continued Isolation of Bovine Granulosa Cells: Ovaries obtained from a slaughter 10 ng/mL IGF-1 100 ng/mL IGF-1 Infertility, often attributed to follicular atresia, is a growing problem in the agricultural industry. house were dissected to obtain follicles 2-5 mm in diameter. The follicles Programmed cell death, also known as apoptosis, is a contributing factor of follicular atresia.
    [Show full text]
  • Androgens Regulate Ovarian Follicular Development by Increasing Follicle Stimulating Hormone Receptor and Microrna-125B Expression
    Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression Aritro Sena,b,1, Hen Prizanta, Allison Lighta, Anindita Biswasa, Emily Hayesa, Ho-Joon Leeb, David Baradb, Norbert Gleicherb, and Stephen R. Hammesa,1 aDivision of Endocrinology and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; and bCenter for Human Reproduction, New York, NY 10021 Edited by John J. Eppig, Jackson Laboratory, Bar Harbor, ME, and approved January 15, 2014 (received for review October 8, 2013) Although androgen excess is considered detrimental to women’s promoting preantral follicle growth and development into an- health and fertility, global and ovarian granulosa cell-specific an- tral follicles. However, these in vivo studies did not elucidate drogen-receptor (AR) knockout mouse models have been used to specific mechanisms used by androgens and ARs to mediate show that androgen actions through ARs are actually necessary these processes. for normal ovarian function and female fertility. Here we describe Here we performed an in-depth analysis of androgen-induced two AR-mediated pathways in granulosa cells that regulate ovar- signaling pathways that regulate ovarian folliculogenesis. Andro- ian follicular development and therefore female fertility. First, we gens signal via extranuclear (nongenomic) and nuclear (genomic) show that androgens attenuate follicular atresia through nuclear pathways. In fact, previous work by others and ourselves in and extranuclear signaling pathways by enhancing expression of androgen-sensitive prostate cancer cells showed that these two the microRNA (miR) miR-125b, which in turn suppresses proapop- processes are tightly linked, with maximal AR-mediated nuclear totic protein expression.
    [Show full text]
  • Germinal Vesiclebreakdown in Oocytes of Human Atretic Follicles
    Germinal vesicle breakdown in oocytes of human atretic follicles during the menstrual cycle A. Gougeon and J. Testart Physiologie et Psychologie de la Reproduction humaine, INSERM U-187, 32 rue des Carnets, 92140 Clamart, France Summary. Histological examination was performed on 975 antral follicles (1\p=n-\12mm) from 17 large ovarian resections and 79 whole ovaries collected from 63 women with normal ovarian function at different stages during the menstrual cycle. The meiotic stage of the oocyte was examined in relation to the degree of atresia and size of follicles throughout the menstrual cycle. In healthy follicles the oocytes were in the dictyate stage. In atretic follicles 10% of the oocytes exhibited germinal vesicle breakdown (GVBD) and 20% were necrotic. The percentage of GVBD oocytes in atretic follicles was closely related to the degree of follicular atresia and to the follicle diameter. GVBD percentage rose sharply in the periovulatory period although there was no change of mean follicle size or quality during this period. Such a cyclic evolution in GVBD per- centages indicates that the removal of inhibition (due to atresia) exerted by the follicle itself on the germinal vesicle is insufficient to induce the resumption of meiosis in the human oocyte; specific induction seems to be necessary, at least to produce complete nuclear maturation. Introduction In mammals, meiosis is initiated in oocytes during fetal development but becomes arrested in late prophase (dictyate stage) at about the time of birth. At this moment the oocyte contains a large nucleus called the germinal vesicle (GV). It is generally accepted that the resumption of the arrested first meiotic division (germinal vesicle breakdown: GVBD) results from the LH surge during each ovarian cycle, but also occurs spontaneously in atretic ovarian follicles (Ingram, 1962).
    [Show full text]
  • Role of FSH in Regulating Granulosa Cell Division and Follicular Atresia in Rats J
    Role of FSH in regulating granulosa cell division and follicular atresia in rats J. J. Peluso and R. W. Steger Reproductive Physiology Laboratories, C. S. Moti Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan 48201, U.S.A. Summary. The effects of PMSG on the mitotic activity of granulosa cells and atresia of large follicles in 24-day-old rats were examined. The results showed that the labelling index (1) decreased in atretic follicles parallel with a loss of FSH binding, and (2) in- creased in hypophysectomized rats treated with FSH. It is concluded that FSH stimu- lates granulosa cell divisions and that atresia may be caused by reduced binding of FSH to the granulosa cells. Introduction Granulosa cells of primary follicles undergo repeated cell divisions and thus result in the growth of the follicle (Pederson, 1972). These divisions are stimulated by FSH and oestrogen, but FSH is also necessary for antrum formation (Goldenberg, Vaitukaitus & Ross, 1972). The stimulatory effects of FSH on granulosa cell divisions may be mediated through an accelerated oestrogen synthesis because FSH induces aromatizing enzymes and enhances oestrogen synthesis within the granulosa cells (Dorrington, Moon & Armstrong, 1975; Armstrong & Papkoff, 1976). Although many follicles advance beyond the primordial stage, most undergo atresia (Weir & Rowlands, 1977). Atretic follicles are characterized by a low mitotic activity, pycnotic nuclei, and acid phosphatase activity within the granulosa cell layer (Greenwald, 1974). The atresia of antral follicles occurs in three consecutive stages (Byskov, 1974). In Stage I, there is a slight reduction in the frequency of granulosa cell divisions and pycnotic nuclei appear.
    [Show full text]
  • Center for Studies in Demography and Ecology Menstrual Cycle
    Center for Studies in Demography and Ecology Menstrual Cycle Variability and the Perimenopause by Kathleen A. O'Connor University of Washington Pennsylvania State University Darryl J. Holman University of Washington Pennsylvania State University James W. Wood Pennsylvania State University UNIVERSITY OF WASHINGTON CSDE Working Paper No. 00-06 Menstrual Cycle Variability and the Perimenopause Kathleen A. O'Connor1, 3 Darryl J. Holman1, 3 James W. Wood2, 3 1Department of Anthropology Center for Studies of Demography and Ecology University of Washington Seattle, WA 98195, USA. 2Department of Anthropology 3Population Research Institute Pennsylvania State University University Park, PA 16802, USA We thank Eleanor Brindle, Susannah Barsom, Kenneth Campbell, Fortüne Kohen, Bill Lasley, John O’Connor, Phyllis Mansfield, and Cheryl Stroud for their assistance with the laboratory component of this work. Anti-human LHβ1 and FSHβ antisera (AFP #1) and LH (AFP4261A) and FSH (LER907) standards were provided by the National Hormone and Pituitary Program through NIDDK, NICHD, and USDA. 1 Abstract Menopause, the final cessation of menstrual cycling, occurs when the pool of ovarian follicles is depleted. The one to five years just prior to the menopause are usually marked by increasing variability in menstrual cycle length, frequency of ovulation, and levels of reproductive hormones. Little is known about the mechanisms that account for these characteristics of ovarian cycles as the menopause approaches. Some evidence suggests that the dwindling pool of follicles itself is responsible for cycle characteristics during the perimenopausal transition. Another hypothesis is that the increased variability reflects "slippage" of the hypothalamus, which loses the ability to regulate menstrual cycles at older reproductive ages.
    [Show full text]
  • Genetic Relationships Between Early Menopause and the Behaviour of Theca Interna During Follicular Atresia
    Human Reproduction, Vol.0, No.0, pp. 1–3, 2020 doi:10.1093/humrep/deaa173 OPINION Genetic relationships between early Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaa173/5892245 by Univ of Rochester Library user on 26 August 2020 menopause and the behaviour of theca interna during follicular atresia Raymond J. Rodgers1,* and Joop S.E. Laven2 1Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia 2Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, Netherlands *Correspondence address. Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. E-mail: [email protected] Submitted on April 26, 2020; resubmitted on May 24, 2020; editorial decision on June 8, 2020 ABSTRACT: Genetic variants are known to contribute to about 50% of the heritability of the age of menopause and recent studies sug- gest that genes associated with genome maintenance are involved. The idea that increased rates of follicular atresia could lead to depletion of the primoridial follicle reserve and early menopause has also been canvassed, but there is no direct evidence of this. In studies of the transcriptomics of follicular atresia, it was found that in the theca interna, the largest group of genes are in fact down-regulated and associ- ated with ‘cell cycle and DNA replication’, in contrast with the up-regulation of apoptosis-associated genes which occurs in granulosa cells. Many of the genes down-regulated in the theca interna are the same as or related to the genes in loci associated with early menopause.
    [Show full text]
  • Meta-Analysis of Gene Expression Profiles in Granulosa Cells During Folliculogenesis
    REPRODUCTIONREVIEW Meta-analysis of gene expression profiles in granulosa cells during folliculogenesis Daulat Raheem Khan1, Éric Fournier1, Isabelle Dufort1, François J Richard1, Jaswant Singh2 and Marc-André Sirard1 1Centre de Recherche en Biologie de la Reproduction, Département des Sciences Animales, Faculté des sciences de l’agriculture et de l’alimentation, Université Laval, Quebec City, Québec, Canada, and 2Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Correspondence should be addressed to M-A Sirard; Email: [email protected] Abstract Folliculogenesis involves coordinated profound changes in different follicular compartments and significant modifications of their gene expression patterns, particularly in granulosa cells. Huge datasets have accumulated from the analyses of granulosa cell transcriptomic signatures in predefined physiological contexts using different technological platforms. However, no comprehensive overview of folliculogenesis is available. This would require integration of datasets from numerous individual studies. A prerequisite for such integration would be the use of comparable platforms and experimental conditions. The EmbryoGENE program was created to study bovine granulosa cell transcriptomics under different physiological conditions using the same platform. Based on the data thus generated so far, we present here an interactive web interface called GranulosaIMAGE (Integrative Meta-Analysis of Gene Expression), which provides dynamic expression profiles of any gene of interest and all isoforms thereof in granulosa cells at different stages of folliculogenesis. GranulosaIMAGE features two kinds of expression profiles: gene expression kinetics during bovine folliculogenesis from small (6 mm) to pre-ovulatory follicles under different hormonal and physiological conditions and expression profiles of granulosa cells of dominant follicles from post-partum cows in different metabolic states.
    [Show full text]
  • Preantral Follicular Atresia Occurs Mainly Through Autophagy, While Antral Follicles Degenerate Mostly Through Apoptosis
    Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis Meng, L., Jan, S. Z., Hamer, G., van Pelt, A. M., van der Stelt, I., Keijer, J., & Teerds, K. J. This is a "Post-Print" accepted manuscript, which has been published in "Biology of Reproduction" This version is distributed under a non-commercial no derivatives Creative Commons (CC-BY-NC-ND) user license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and not used for commercial purposes. Further, the restriction applies that if you remix, transform, or build upon the material, you may not distribute the modified material. Please cite this publication as follows: Meng, L., Jan, S. Z., Hamer, G., van Pelt, A. M., van der Stelt, I., Keijer, J., & Teerds, K. J. (2018). Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis. Biology of Reproduction, 99(4), 853-863. DOI: 10.1093/biolre/ioy116 You can download the published version at: https://doi.org/10.1093/biolre/ioy116 1 Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis Running title: Autophagy, apoptosis and follicular atresia Summary sentence: Preantral and antral follicles make use of different cell death pathways, as antral follicular degeneration is initiated by massive granulosa cell apoptosis, while preantral follicular atresia is mainly dependent on enhanced granulosa cell autophagy Apoptosis, autophagy, atresia, preantral and antral follicles, granulosa cells, mitochondria, ovary Key words: Li Menga,b, Sabrina Z. Jan c, Geert Hamerc, Ans M. van Peltc, Inge van der Stelta, Jaap Keijera, Katja J.
    [Show full text]
  • Human Placental Extracts Improve Ovarian Function by Reducing Follicular Atresia in Mice with CTX-Induced Premature Ovarian Fail
    r Biomar ula ke c rs Zhang et al., J Mol Biomark Diagn 2017, 9:1 le o & M D f i a DOI: 10.4172/2155-9929.1000373 o g l Journal of Molecular Biomarkers n a o n r s i u s o J ISSN: 2155-9929 & Diagnosis Research Article Open Access Human Placental Extracts Improve Ovarian Function by Reducing Follicular Atresia in Mice With CTX-Induced Premature Ovarian Failure Bao-Fang Zhang1,2#, Lei Yu2#, YongMei Liu2, Xue Ke Zhao2, Li Li Zhu2, Ming-Liang Cheng2* and YaXin Hu2 1The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, P.R China 2The Affiliated Hospital, Guizhou Medical University, Beijing, Guiyang, Guizhou, P.R China #These authors contributed equally to this work and should be considered as co-first authors Abstract The details of the pathogenic mechanisms underlying premature ovarian failure (POF) remain unknown. Accumulating evidence suggests that primordial follicle inactivity, disorders affecting follicular survival and growth and follicular atresia may affect an individual’s susceptibility to POF. The Rictor/mTORC2/Akt/Foxo3a pathway plays a central role in cytoskeletal construction and follicle survival. As a stronger alkylating agent that exerts immunosuppressive effects, cyclophosphamide (CTX) is widely used in clinical practice, especially in cancer. However, it also has significant reproductive toxicity. CTX accelerates the development of ovarian follicles into mature follicles, resulting in a decreased follicular reserve and ultimately leading to ovarian failure or even POF. We have sought to research effective methods to reduce the damage caused by CTX. Here, we investigated the protective role of human placental extracts on CTX-induced ovarian injury in mice.
    [Show full text]
  • Newly Identified Regulators of Ovarian Folliculogenesis and Ovulation
    International Journal of Molecular Sciences Review Newly Identified Regulators of Ovarian Folliculogenesis and Ovulation Eran Gershon 1 and Nava Dekel 2,* 1 Department of Ruminant Science, Agricultural Research Organization, PO Box 6, Rishon LeZion 50250, Israel; [email protected] 2 Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel * Correspondence: [email protected] Received: 7 May 2020; Accepted: 23 June 2020; Published: 26 June 2020 Abstract: Each follicle represents the basic functional unit of the ovary. From its very initial stage of development, the follicle consists of an oocyte surrounded by somatic cells. The oocyte grows and matures to become fertilizable and the somatic cells proliferate and differentiate into the major suppliers of steroid sex hormones as well as generators of other local regulators. The process by which a follicle forms, proceeds through several growing stages, develops to eventually release the mature oocyte, and turns into a corpus luteum (CL) is known as “folliculogenesis”. The task of this review is to define the different stages of folliculogenesis culminating at ovulation and CL formation, and to summarize the most recent information regarding the newly identified factors that regulate the specific stages of this highly intricated process. This information comprises of either novel regulators involved in ovarian biology, such as Ube2i, Phoenixin/GPR73, C1QTNF, and α-SNAP, or recently identified members of signaling pathways previously reported in this context, namely PKB/Akt, HIPPO, and Notch. Keywords: folliculogenesis; ovulation 1. Folliculogenesis Folliculogenesis is initiated during fetal life. The migration of the primordial germ cells (PGCs) to the embryonic genital ridge [1] may, in fact, be considered as the earliest event along this process.
    [Show full text]
  • Androgen Actions in the Ovary 222:3 R141–R151 Review
    H PRIZANT and others Androgen actions in the ovary 222:3 R141–R151 Review Androgen actions in the ovary: balance is key Correspondence 1 2 1,2 Hen Prizant , Norbert Gleicher and Aritro Sen should be addressed to A Sen 1Division of Endocrinology and Metabolism, Department of Medicine, University of Rochester School of Medicine Email and Dentistry, 601 Elmwood Avenue, PO Box 693, Rochester, New York 14642, USA aritro_sen@urmc. 2Center for Human Reproduction, New York, New York 10021, USA rochester.edu Abstract For many decades, elevated androgens in women have been associated with poor Key Words reproductive health. However, recent studies have shown that androgens play a crucial " androgen role in women’s fertility. The following review provides an overall perspective about " androgen receptor how androgens and androgen receptor-mediated actions regulate normal follicular " female reproduction development, as well as discuss emerging concepts, latest perceptions, and controversies " ovary regarding androgen actions and signaling in the ovary. Journal of Endocrinology (2014) 222, R141–R151 Introduction Journal of Endocrinology Recently, there has been a lot of interest towards the role ovarian insufficiency (POI), thereby negatively impacting of androgens in the regulation of follicular development female fertility. Many studies (Kimura et al. 2007, Walters and female fertility. In fact, over the years our under- et al. 2008, 2010, Gleicher et al. 2011, Sen & Hammes 2011, standing of the effects of androgens on follicular develop- Lebbe & Woodruff 2013) in the past 5 years have addressed ment and female fertility has undergone considerable androgen actions in the ovary. In this review, we change. Androgens have traditionally been considered summarize what currently is known about the direct detrimental to ovarian function and are often associated physiological actions of androgens in the regulation of with infertility.
    [Show full text]
  • Histological Study of Follicular Atresia in Theovary of The
    Histological study of follicular atresia in the ovary of the domestic hen (Gallus domesticus) S. K. Gupta, A. B. Gilbert and M. A. Walker AFRC Institute of Animal Physiology and Genetics Research, Edinburgh Research Station, Roslin, Midlothian EH25 9PS, U.K. Summary. Semi-serial (1 in 20) sections of ovaries were studied and only two types of atresia were identified\p=m-\non-burstingand bursting. Smaller, non-yolky follicles (< 1 mm diameter) showed non-bursting atresia. Atresia in follicles > 1 mm diameter was invariably of the bursting type which involved the rupture of the follicular wall, and the extrusion of yolk and cellular debris through the rupture site into the stroma. However, this rupture site was small and consequently was not visible in every section but it could always be seen when the follicle was followed in semi-serial sections. The mitotic index of granulosa cells in bursting atretic follicles was much lower than that for normal follicles. The most common criteria for distinguishing non-bursting atretic follicles were the extremely shrunken, irregularly shaped oocytes and the separation of the granulosa from the theca. In bursting atretic follicles, reliable indications were the presence in the ooplasm of some cells or cellular debris, and disorganization of the yolk and granulosa tissue. The presence of pycnotic nuclei in the granulosa cells was not a consistent feature of all atretic follicles of the hen. Keywords: hen; follicles; atresia; histology Introduction Unlike mammals (Byskov, 1978; Ryan, 1981; Guraya, 1985), histological criteria for the identi¬ fication of atretic follicles in the avian ovary are not well established.
    [Show full text]