Abstract:
BACKGROUND:Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology. It also discusses interesting advances in the field of modulating the bioactivity of activins as a therapeutic target, which would undoubtedly be beneficial for patients with reproductive pathology. METHODS:A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies in the English language which have contributed to the advancement of the field of activin biology, since its initial isolation in 1987 until July 2015. 'Activin', 'testis', 'ovary', 'embryonic development' and 'therapeutic targets' were used as the keywords in combination with other search phrases relevant to the topic of activin biology. RESULTS:Activins, which are dimers of inhibin β subunits, act via a classical TGF-β signalling pathway. The bioactivity of activin is regulated by two endogenous inhibitors, inhibin and follistatin. Activin is a major regulator of testicular and ovarian development. In the ovary, activin A promotes oocyte maturation and regulates granulosa cell steroidogenesis. It is also essential in endometrial repair following menstruation, decidualization and maintaining pregnancy. Dysregulation of the activin-follistatin-inhibin system leads to disorders of female reproduction and pregnancy, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, fetal growth restriction, gestational diabetes, pre-eclampsia and pre-term birth. Moreover, a rise in serum activin A, accompanied by elevated FSH, is characteristic of female reproductive aging. In the male, activin A is an autocrine and paracrine modulator of germ cell development and Sertoli cell proliferation. Disruption of normal activin signalling is characteristic of many tumours affecting reproductive organs, including endometrial carcinoma, cervical cancer, testicular and ovarian cancer as well as prostate cancer. While activin A and B aid the progression of many tumours of the reproductive organs, activin C acts as a tumour suppressor. Activins are important in embryonic induction, morphogenesis of branched glandular organs, development of limbs and nervous system, craniofacial and dental development and morphogenesis of the Wolffian duct. CONCLUSIONS:The field of activin biology has advanced considerably since its initial discovery as an FSH stimulating agent. Now, activin is well known as a growth factor and cytokine that regulates many aspects of reproductive biology, developmental biology and also inflammation and immunological mechanisms. Current research provides evidence for novel roles of activins in maintaining the structure and function of reproductive and other organ systems. The fact that activin A is elevated both locally as well as systemically in major disorders of the reproductive system makes it an important biomarker. Given the established role of activin A as a pro-inflammatory and pro-fibrotic agent, studies of its involvement in disorders of reproduction resulting from these processes should be examined. Follistatin, as a key regulator of the biological actions of activin, should be evaluated as a therapeutic agent in conditions where activin A overexpression is established as a contributing factor.
journal_name
Hum Reprod Updatejournal_title
Human reproduction updateauthors
Wijayarathna R,de Kretser DMdoi
10.1093/humupd/dmv058subject
Has Abstractpub_date
2016-04-01 00:00:00pages
342-57issue
3eissn
1355-4786issn
1460-2369pii
dmv058journal_volume
22pub_type
杂志文章,评审abstract::In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by com...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/6.4.322
更新日期:2000-07-01 00:00:00
abstract::Apoptosis is a selective process for deletion of cells in various biological systems. This event, similar to proliferation, is tightly regulated, with both processes playing essential roles in the homeostasis of renewable tissues. In human endometrium, proliferation and apoptosis occur at opposing poles of the menstru...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/1.4.303
更新日期:1995-07-01 00:00:00
abstract::Insulin-like growth factor-1 (IGFBP-1) is particularly important in human female reproductive physiology, where it is involved with other factors in a complex system which regulates menstrual cycles, puberty, ovulation, decidualization, implantation and fetal growth. This has implications for clinical obstetrics and g...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/6.5.495
更新日期:2000-09-01 00:00:00
abstract::Following its benchmark discovery, nitric oxide (NO) is now known to play important functional roles in a variety of physiological systems. Within the vasculature, NO induces vasodilation, inhibits platelet aggregation, prevents neutrophil/platelet adhesion to endothelial cells, inhibits smooth muscle cell proliferati...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/4.1.3
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific min...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmr005
更新日期:2011-07-01 00:00:00
abstract::The improved long-term survival of adolescents and young women treated for cancer has resulted in an increased focus on the effects of chemotherapy on ovarian function and its preservation. These women may seek advice and treatment regarding their reproductive status, including ways of preserving their fertility and p...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmh052
更新日期:2005-01-01 00:00:00
abstract::Syncytin is a membrane protein derived from the envelope gene of an endogenous retrovirus of the HERV-W family. The gene appears to be almost exclusively expressed in placenta; the protein was found in particular in syncytiotrophoblast. After transfection into various cell types it has proven to be a very fusogenic pr...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmh039
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Thyroid hormone disorders and thyroid peroxidase autoantibodies (TPO-Ab) in women are associated with subfertility and early pregnancy loss. Here, we aim to provide a comprehensive overview of the literature on the pathophysiology of these associations. METHODS:A review of the literature in the English lang...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmv004
更新日期:2015-05-01 00:00:00
abstract::Polychlorinated dioxins, furans and polychlorinated benzene constitute a family of toxic persistent environmental pollutants. In Europe, environmental concentrations increased slowly throughout this century until the late 1980s. Dioxins have been shown to be carcinogenic in animals and humans. In humans, excess risks ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/7.3.331
更新日期:2001-05-01 00:00:00
abstract:UNLABELLED:BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many ye...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析,评审
doi:10.1093/humupd/dmt038
更新日期:2014-01-01 00:00:00
abstract::This report describes the ethical and legal aspects of assisted reproductive technologies (ART) that have been instituted in European countries. The data were collected from questionnaires circulated to fertility centres in 39 countries in Europe. Ninety six ART centres were located in 30 of these countries. Nine coun...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/3.2.173
更新日期:1997-03-01 00:00:00
abstract::The number of cell divisions during embryonic and fetal life makes the embryo/fetus particularly vulnerable to effects resulting from exposure to an adverse intrauterine environment. Exposure to drugs and irradiation at this stage of development are able to cause congenital malformations and various cancers in later l...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/6.6.578
更新日期:2000-11-01 00:00:00
abstract::Maternal use of marijuana, in which the exocannabinoid Delta(9)-tetrahydrocannabinol is the most active psychoactive ingredient, is known to have adverse effects on various aspects of reproduction including ovulation, spermatogenesis, implantation and pregnancy duration. Endogenous cannabinoids of which Anandamide is ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmm018
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of f...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmy003
更新日期:2018-05-01 00:00:00
abstract::Ovarian follicular development occurs in a hierarchical manner with each follicle having a unique biochemical composition at any moment in time. It has long been understood that a precise coordination between the growth and maturation of the oocyte and adjacent follicular cells (i.e. somatic cells) is essential in ord...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmh061
更新日期:2005-03-01 00:00:00
abstract::Follicle stimulating hormone (FSH) is one of the two pituitary gonadotrophins involved in the regulation of gonadal function. Structurally, this gonadotrophin is a heterodimer composed of two non-covalently associated subunits containing several heterogenous oligosaccharide residues which play an important role in bot...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/4.3.260
更新日期:1998-05-01 00:00:00
abstract::Cryopreservation of testicular tissue might benefit prepubertal boys who must undergo chemotherapy or radiotherapy. Cryopreservation of testicular tissue and testicular cells for intracytoplasmic sperm injection (ICSI) is feasible and widely applied. Testicular tissue from prepubertal boys can also be frozen, by apply...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/7.4.378
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modu...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dms004
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complicatio...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析
doi:10.1093/humupd/dmz012
更新日期:2019-09-11 00:00:00
abstract::In 1987, Nigel Harris cautioned against over-diagnosing the antiphospholipid syndrome (APS). In what was a rather prophetic editorial titled 'The Syndrome of the Black Swan', he suggested that while patients with APS do indeed exist, they are probably much more unusual than many medical professionals might like to bel...
journal_title:Human reproduction update
pub_type: 社论
doi:10.1093/humupd/dms020
更新日期:2012-09-01 00:00:00
abstract::Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmm043
更新日期:2008-03-01 00:00:00
abstract::Hormonal contraception has become more effective and more widely used, while the world population has grown from 3000 million in 1960 to 6000 million in 2000. There is a need for improved contraception, because legal abortion is used in a high proportion of pregnancies and illegal abortion continues to be common in so...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/8.4.359
更新日期:2002-07-01 00:00:00
abstract::From a public health viewpoint, the intrauterine device (IUD) is the most widely used contraceptive method in the world. Prevalence rates range among countries from 2 to 80% of contraceptive users. During 5 years of IUD use, pregnancy occurs in less than 2 per 100 insertions. Bleeding and pain are the most common reas...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmn003
更新日期:2008-05-01 00:00:00
abstract::In the male genital tract, reactive oxygen species (ROS) are generated by spermatozoa and leukocytes including neutrophils and macrophages. ROS are involved in the regulation of sperm functions such as capacitation and the acrosome reaction. Infections lead to an excessive ROS production, resulting in an 'oxidative bu...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/5.5.399
更新日期:1999-09-01 00:00:00
abstract:BACKGROUND:The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatmen...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmt037
更新日期:2014-01-01 00:00:00
abstract::Single-dose and multiple-rising dose studies of recombinant follicle stimulating hormone (rFSH) in hypogonadotrophic male and female volunteers demonstrated that the rate of FSH absorption after i.m. injection is higher in men than in women. In the absence of endogenous FSH, a correlation between serum FSH and body we...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/2.2.153
更新日期:1996-03-01 00:00:00
abstract::We have examined aspects of the fine structure of the basal laminae associated with the luminal and glandular epithelium and small blood vessels in the human endometrium. Four short studies are presented and reviewed. Study 1 examined biopsies from 20 fertile women taken on days after the luteinizing hormone surge (LH...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/4.5.486
更新日期:1998-09-01 00:00:00
abstract::Protamines are the major nuclear sperm proteins. The human sperm nucleus contains two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single gene that is transcribed and translated into a precursor protein. The protam...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dml009
更新日期:2006-07-01 00:00:00
abstract::As soon as leptin was discovered four years ago, its potential as a player in the polycystic ovary syndrome (PCOS) was explored in a primitive way, though little light was shed on the enigma that is PCOS. As a second wave of leptin research is now available, we review how the expanded role of the cytokine in reproduct...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/5.2.166
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:The aim of this meta-analysis was to investigate whether any difference exists in success rate of clinical outcomes of assisted reproductive technologies (ART) between women who actively smoke cigarettes at the time of treatment and those who do not. METHODS:An intensive computerized search was conducted on...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析,评审
doi:10.1093/humupd/dmn046
更新日期:2009-01-01 00:00:00