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Topic:Insulin-Like Growth Factor

Insulin-Like Growth Factor (IGF) in horses refers to a group of hormones that play a significant role in growth and development. These proteins, primarily produced in the liver, are part of the endocrine system and are involved in cell growth, differentiation, and metabolism. In equine physiology, IGF is associated with muscle development, bone growth, and overall body condition. The levels of IGF can be influenced by factors such as age, nutrition, and exercise, making them a point of interest in studies related to performance and health in horses. This page compiles peer-reviewed research studies and scholarly articles that explore the function, regulation, and implications of Insulin-Like Growth Factor in equine biology and veterinary practice.
Selecting potential biomarkers of plasma proteins in mares with endometritis.
Equine veterinary journal    April 14, 2024   doi: 10.1111/evj.14092
Zhang X, Mai Z, Gao Y, Zhao X, Zhang Y.Endometritis is a common condition in mares that causes significant economic loss. Lacking obvious clinical signs, the clinical diagnosis of endometritis in mares relies on case-by-case clinical examinations, which can be particularly inefficient in large-scale farms. Therefore, the identification of potential biomarkers can serve as a non-invasive and efficient screening technique for endometritis in mares. Objective: To compare the blood proteome between fertile mares and mares with endometritis to identify biomarkers potentially associated with the development of endometritis and validate t...
Short-term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin-sensitive ponies.
Equine veterinary journal    October 6, 2023   doi: 10.1111/evj.14012
Barnabé MA, Elliott J, Harris PA, Menzies-Gow NJ.Hypoadiponectinaemia is a risk factor for endocrinopathic laminitis, but the directionality and nature of its association with insulin dysregulation is unclear. Objective: To investigate the effects of short-term induced hyperinsulinaemia and dexamethasone challenge on circulating [total adiponectin] and whole blood expression of adiponectin (AdipoR1 and AdipoR2), insulin, and insulin-like growth factor 1 (IGF-1) receptors in insulin-sensitive ponies. Methods: In vivo experiment. Methods: Six never-laminitic, insulin-sensitive, native-breed UK ponies first underwent a dexamethasone challenge (...
Effects of insulin-like growth factor-1 on the proliferation and apoptosis of stallion testicular cells under normal and heat stress culture conditions.
Animal reproduction science    August 15, 2023   Volume 256 107319 doi: 10.1016/j.anireprosci.2023.107319
Shakeel M, Yoon M.This study investigated the effect of heat stress on stallion testicular cells (TCs) and the effect of insulin-like growth factor (IGF)-1 on TC viability, proliferation, and apoptosis, including different stages of germ cells. TCs were divided into control or treatment groups with 0.01, 0.1, 1, 10, and 100 ng/mL of recombinant human IGF-1 (rhIGF-1) for 24 h at 34 °C and 37 °C. The population and viability were measured before and after treatment. The effects of rhIGF-1 on TC viability, proliferation, and apoptosis were determined using RT-qPCR. Proliferating cell nuclear antigen (PCNA) a...
Growth Factor Roles in Soft Tissue Physiology and Pathophysiology.
Advances in experimental medicine and biology    November 23, 2021   Volume 1348 139-159 doi: 10.1007/978-3-030-80614-9_6
Roberts JH, Halper J.Repair and healing of injured and diseased tendons has been traditionally fraught with apprehension and difficulties, and often led to rather unsatisfactory results. The burgeoning research field of growth factors has opened new venues for treatment of tendon disorders and injuries, and possibly for treatment of disorders of the aorta and major arteries as well. Several chapters in this volume elucidate the role of transforming growth factor β (TGFß) in pathogenesis of several heritable disorders affecting soft tissues, such as aorta, cardiac valves, and tendons and ligaments. Several member...
Influence of Incubation Time and Incubation Tube on the Cytokine and Growth Factor Concentrations of Autologous Conditioned Serum in Horses.
Journal of equine veterinary science    January 8, 2019   Volume 75 30-34 doi: 10.1016/j.jevs.2018.12.015
Lasarzik de Ascurra J, Ehrle A, Einspanier R, Lischer C.Autologous conditioned serum (ACS) is commonly used for the treatment of human and equine osteoarthritis (OA). The objective of this study was to investigate the influence of incubation time and incubation tube on concentrations of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 beta (IL-1β), and insulin-like growth factor-1 (IGF-1) in ACS of horses with and without OA. Blood samples of 7 control horses and 6 horses with naturally occurring OA were obtained. The concentration of serum IL-1ra, IL-1β, and IGF-1 was determined after 12, 24, and 36 hours of incubation using commercial ...
Polymorphisms in selected genes and analysis of their relationship with osteochondrosis in Polish sport horse breeds.
Animal genetics    August 28, 2018   Volume 49, Issue 6 623-627 doi: 10.1111/age.12715
Wypchło M, Korwin-Kossakowska A, Bereznowski A, Hecold M, Lewczuk D.The aim of this research was to evaluate the polymorphisms of selected genes and to find their potential effect on the occurrence of osteochondrosis in Polish Warmbloods (sport horse breeds). The study was conducted on a group of 198 horses subjected to official performance tests. Investigated joints-fetlock, hock and stifle-were X-rayed twice, once before and again at the end of the tests (first and second examination), and on this basis the degree of disease was evaluated. Based on the results of previous research, 13 candidate genes potentially associated with the occurrence of osteochondro...
Systemic and intrafollicular components of follicle selection in mares.
Domestic animal endocrinology    December 22, 2016   Volume 59 116-133 doi: 10.1016/j.domaniend.2016.12.005
Ginther OJ.Mares are superb models for study of follicle selection owing to similarities between mares and women in relative follicle diameters at specific events during the follicular wave and follicle accessibility for experimental sampling and manipulation. Usually, only 1 major follicular wave with a dominant follicle (DF) greater than 30 mm develops during the 22 to 24 d of the equine estrous cycle and is termed the primary or ovulatory wave. A major secondary wave occasionally (25%) develops early in the cycle. Follicles of the primary wave emerge at 6 mm on day 10 or 11 (day 0 = ovulation). The...
Selection signatures in Shetland ponies.
Animal genetics    February 9, 2016   Volume 47, Issue 3 370-372 doi: 10.1111/age.12416
Frischknecht M, Flury C, Leeb T, Rieder S, Neuditschko M.Shetland ponies were selected for numerous traits including small stature, strength, hardiness and longevity. Despite the different selection criteria, Shetland ponies are well known for their small stature. We performed a selection signature analysis including genome-wide SNPs of 75 Shetland ponies and 76 large-sized horses. Based upon this dataset, we identified a selection signature on equine chromosome (ECA) 1 between 103.8 Mb and 108.5 Mb. A total of 33 annotated genes are located within this interval including the IGF1R gene at 104.2 Mb and the ADAMTS17 gene at 105.4 Mb. These two ge...
Prolonged hyperinsulinemia affects metabolic signal transduction markers in a tissue specific manner.
Domestic animal endocrinology    November 19, 2015   Volume 55 41-45 doi: 10.1016/j.domaniend.2015.11.001
Campolo A, de Laat MA, Keith L, Gruntmeir KJ, Lacombe VA.Insulin dysregulation is common in horses although the mechanisms of metabolic dysfunction are poorly understood. We hypothesized that insulin signaling in striated (cardiac and skeletal) muscle and lamellae may be mediated through different receptors as a result of receptor content, and that transcriptional regulation of downstream signal transduction and glucose transport may also differ between tissues sites during hyperinsulinemia. Archived samples from horses treated with a prolonged insulin infusion or a balanced electrolyte solution were used. All treated horses developed marked hyperin...
Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    September 8, 2015   Volume 34, Issue 1 149-153 doi: 10.1002/jor.23038
Griffin DJ, Ortved KF, Nixon AJ, Bonassar LJ.Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing the histologic and biochemical content of cartilage repaired by chondrocyte transplantation. However, there is little to no data on the mechanical performance of IGF-I augmented cartilage grafts. This study evaluated the compressive properties of full-thickness chondral defects in the equine femur repaired with and without IGF-I gene therapy. Animals were randomly assigned to one of three study cohorts based on chondrocyte treatment provided in each defect: (i) IGF-I gene delivered by recombinant adeno-associated...
Energy-related parameters and their association with age, gender, and morphometric measurements in healthy donkeys.
Veterinary journal (London, England : 1997)    March 6, 2015   Volume 204, Issue 2 201-207 doi: 10.1016/j.tvjl.2015.03.004
Mendoza FJ, Estepa JC, Gonzalez-De Cara CA, Aguilera-Aguilera R, Toribio RE, Perez-Ecija A.Donkeys are commonly afflicted by endocrine and metabolic disturbances but few studies have investigated endocrine variables involved in energy regulation and their association with morphometric indices, age or gender in this species. Hemostatic and clinical differences have been demonstrated between horses and donkeys, so to consider both species as metabolically and endocrinologically similar could lead to misdiagnosis. In this study, plasma concentrations of glucose, triglycerides and endocrine factors involved in energy homeostasis (insulin, glucagon, leptin, adiponectin, ghrelin and insul...
Serum insulin-like growth factor 1 in the aging horse.
Veterinary clinical pathology    September 22, 2014   Volume 43, Issue 4 557-560 doi: 10.1111/vcp.12201
Lygren T, Hansen S, Langberg H, Fjeldborg J, Jacobsen S, Nielsen MO, Schjerling P, Markussen B, Thomsen PD, Berg LC.Insulin-like growth factor 1 (IGF-1) has important roles in anabolic processes in the musculoskeletal system and has been reported to decrease with age in both people and horses. Objective: The objective of this study was to determine serum IGF-1 levels in the aging horse from early to late adulthood (age range 5-27 years). Methods: Healthy horses (n = 72) were used in a cross-sectional study, while 37 paired serum samples were available for a longitudinal study. Serum IGF-1 protein was determined using an ELISA kit validated for use in equine samples. Results: No association was found betw...
The influence of age on bone metabolism in mares during late pregnancy and lactation.
Research in veterinary science    July 9, 2014   Volume 97, Issue 2 194-198 doi: 10.1016/j.rvsc.2014.06.005
Filipović N, Stojević Z, Plevnik N, Mašek T, Prvanović N, Tuček Z.The concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTx), osteocalcin (OCN), parathyroid hormone (PTH) and insulin-like growth factor (IGF-I) were measured in the blood serum of two age groups of mares during late pregnancy (70-50 days before foaling), during early lactation and at the peak of lactation (10-30 and 55-80 days after foaling, respectively). During late pregnancy, the PTH was higher in older (8-19 years old), compared to younger animals (3.5-4 years old) (P < 0.05). The OCN was higher in younger group during late pregnancy (P < 0.05). IGF-I was...
Surgical stress influences cytokine content in autologous conditioned serum.
Equine veterinary journal    May 26, 2014   Volume 47, Issue 2 212-217 doi: 10.1111/evj.12277
Fjordbakk CT, Johansen GM, Løvås AC, Oppegård KL, Storset AK.No recommendations have been made regarding the relative timing of blood collection for autologous conditioned serum (ACS) preparation and surgical procedures. Objective: 1) To identify effects of surgical stress on cytokine levels in ACS, 2) identify haematological markers for prediction of cytokine production in ACS and 3) investigate the necessity for specialised ACS containers when preparing a cytokine-rich serum. Methods: Experimental in vitro study. Methods: Blood was drawn from 15 stallions admitted for elective castration preoperatively and 22-24 h post operatively and incubated in A...
Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue.
The Onderstepoort journal of veterinary research    January 9, 2014   Volume 80, Issue 1 402 doi: 10.4102/ojvr.v80i1.402
Hughes SB, Quan M, Guthrie A, Schulman M.The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins) and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism a...
MicroRNA-140 expression during chondrogenic differentiation of equine cord blood-derived mesenchymal stromal cells.
Stem cells and development    January 15, 2013   Volume 22, Issue 8 1288-1296 doi: 10.1089/scd.2012.0411
Buechli ME, Lamarre J, Koch TG.MicroRNAs are a class of short noncoding RNAs that are involved in various biological processes, including differentiation. MicroRNA-140 (miR-140) has been identified as a cartilage-specific microRNA with several targets involved in cartilage development and homeostasis. The aim of this study was to investigate the expression of miR-140 during chondrogenic differentiation of equine cord blood-derived mesenchymal stromal cells (eCB-MSCs). We demonstrate both that miR-140 is highly expressed in normal equine articular cartilage and that eCB-MSCs express significantly higher levels of this microR...
Insulin-like growth factor I: could it be a marker of prematurity in the foal?
Theriogenology    December 4, 2012   Volume 79, Issue 3 495-501 doi: 10.1016/j.theriogenology.2012.11.002
Panzani S, Castagnetti C, Prandi A, Faustini M, Zamboni A, Veronesi MC.Insulin-like growth factor (IGF)-I represents one of the most important growth regulators, playing a central role in fetal and neonatal growth. Plasma IGF-I levels increase rapidly after birth, and they are influenced by numerous factors, including sex, age, nutritional state, and premature birth. The aims of this study were: (1) to evaluate the IGF-I plasma profile in healthy newborn foals during the first 2 weeks of life; (2) to assess the possible influence of sex and birth weight on this hormone; (3) to analyze the percentage increment of IGF-I values in healthy foals; (4) to evaluate the ...
Morphological, haemato-biochemical and endocrine changes in young Standardbreds with ‘maladaptation’ to early training.
Equine veterinary journal. Supplement    May 27, 2011   Issue 38 171-178 doi: 10.1111/j.2042-3306.2010.00273.x
Leleu C, Haentjens F.The demands in the Standardbred trotters industry require young, still growing horses, to be trained well above light exercise level. During that period, the risk of occurrence of energy imbalance and maladaptation to training is high. In man, the lack of energy homeostasis is considered as the basic problem in the development of chronic fatigue. Objective: To find objective biomarkers of early maladaptation to training in young racehorses under field conditions. Methods: Sixty-five 2-year-old Standardbreds were followed during their first 3 months of training in 5 different training centres. ...
Autologous conditioned serum: the comparative cytokine profiles of two commercial methods (IRAP and IRAP II) using equine blood.
Equine veterinary journal    March 11, 2011   Volume 43, Issue 5 516-521 doi: 10.1111/j.2042-3306.2010.00321.x
Hraha TH, Doremus KM, McIlwraith CW, Frisbie DD.Osteoarthritis (OA) is one of the most prevalent and debilitating conditions affecting the horse. Autologous conditioned serum (ACS), commercially available as IRAP and IRAP II, is a recently developed treatment for OA in which plasma is prepared from venous blood by incubation with glass beads for 24 h. This product has been shown to increase anti-inflammatory cytokines and growth factors in human blood. However, data for equine ACS preparations are lacking. Objective: To characterise the protein profiles produced by commercially available ACS systems in equine blood. Methods: Blood was dra...
Assessment of synovial fluid biomarkers in healthy foals and in foals with tarsocrural osteochondrosis.
Veterinary journal (London, England : 1997)    January 8, 2011   Volume 190, Issue 3 390-395 doi: 10.1016/j.tvjl.2010.12.001
de Grauw JC, Donabédian M, van de Lest CH, Perona G, Robert C, Lepage O, Martin-Rosset W, van Weeren PR.Although alterations in biomarkers of cartilage turnover in synovial fluid (SF) have been demonstrated in horses with osteochondrosis (OC), there have been few investigations of such alterations in animals <1 year old. In this study tarsocrural SF samples from foals aged 18, 22 and 52 weeks of age were assessed for: (1) 'turnover' biomarkers of type II collagen (CPII and C2C) and proteoglycan (CS846 and glycosaminoglycans [GAG]); (2) matrix metalloproteinase (MMP) activity; (3) insulin-like growth factor (IGF)-1; (4) transforming growth factor (TGF)-β1; (5) prostaglandin (PG) E(2...
Insulin-like growth factor-I (IGF-I) protects cultured equine Leydig cells from undergoing apoptosis.
Animal reproduction science    October 21, 2010   Volume 122, Issue 3-4 353-358 doi: 10.1016/j.anireprosci.2010.10.001
Yoon MJ, Roser JF.Leydig cells located in the interstitial space of the testicular parenchyma produce testosterone which plays a critical role in the maintenance and restoration of spermatogenesis in many species, including horses. For normal spermatogenesis, maintaining Leydig cells is critical to provide an optimal and constant level of testosterone. Recently, an anti-apoptotic effect of IGF-I in testicular cells in rats has been reported, but a similar effect of IGF-I on equine Leydig cells remains to be elucidated. If IGF-I also protects stallion testicular cells from undergoing apoptosis, then IGF-I may ha...
Short-term feed restriction decreases the systemic and intrafollicular concentrations of leptin and increases the vascularity of the preovulatory follicle in mares.
Theriogenology    March 11, 2010   Volume 73, Issue 9 1202-1209 doi: 10.1016/j.theriogenology.2009.11.032
Gastal MO, Gastal EL, Beg MA, Ginther OJ.The objective of this study was to evaluate the effect of short-term feed restriction on characteristics of the preovulatory follicle and on concentrations of systemic hormones (leptin, follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and follicular fluid hormones and growth factors (leptin, estradiol, inhibin-A, activin-A, free insulin-like growth factor-1 [IGF1], insulin-like growth factor binding protein 2 [IGFBP2], vascular endothelial growth factor [VEGF]). Mares were submitted to a short-term (48 h) feed restriction when the expected ovulatory follicle was > or =27 mm (Hour ...
Normal function of the hypothalamic-pituitary growth axis in three dwarf Friesian foals.
The Veterinary record    September 29, 2009   Volume 165, Issue 13 373-376 doi: 10.1136/vr.165.13.373
de Graaf-Roelfsema E, Back W, Keizer HA, Stout TA, van der Kolk JH.Serial blood samples were collected from three dwarf Friesian foals to examine their endogenous growth hormone (GH) profiles, and the integrity of the GH-insulin-like growth factor-1 (IGF-1) axis was tested in one of them by examining its responses to the administration of GH-releasing hormone (GHRH) and to 10 days of treatment with recombinant equine GH. The basal serum concentrations of IGF-1 in the three dwarf foals were compared with those in nine age-matched normal foals. All the dwarf foals secreted endogenous GH. Stimulation with 7.0 microg/kg GHRH led to a 1400 per cent increase in pla...
Relationships of follicle versus oocyte maturity to ultrasound morphology, blood flow, and hormone concentrations of the preovulatory follicle in mares.
Biology of reproduction    May 2, 2007   Volume 77, Issue 2 202-208 doi: 10.1095/biolreprod.107.061184
Ginther OJ, Gastal EL, Gastal MO, Siddiqui MA, Beg MA.The effects of ultrasound morphology, vascularity, and follicular-fluid hormones of the preovulatory follicle on oocyte recovery rate and on follicle and oocyte maturity rates were studied for 60 spontaneous and solitary preovulatory follicles in mares. An ovulation-inducing dose of hCG was given when the follicle was >or=32 mm (Hour 0), and a procedure for oocyte recovery was done 30 h later (Hour 30). Between Hours 0 and 30, diameter of the follicle increased less and circulating estradiol (E2) concentrations decreased more in groups with successful versus nonsuccessful oocyte recovery an...
Cryptorchidism in common eutherian mammals.
Reproduction (Cambridge, England)    March 24, 2007   Volume 133, Issue 3 541-561 doi: 10.1530/REP-06-0272
Amann RP, Veeramachaneni DN.Cryptorchidism is failure of one or both testes to descend into the scrotum. Primary fault lies in the testis. We provide a unifying cross-species interpretation of testis descent and urge the use of precise terminology. After differentiation, a testis is relocated to the scrotum in three sequential phases: abdominal translocation, holding a testis near the internal inguinal ring as the abdominal cavity expands away, along with slight downward migration; transinguinal migration, moving a cauda epididymidis and testis through the abdominal wall; and inguinoscrotal migration, moving a s.c. cauda...
Follicle selection in cattle and horses: role of intrafollicular factors.
Reproduction (Cambridge, England)    August 31, 2006   Volume 132, Issue 3 365-377 doi: 10.1530/rep.1.01233
Beg MA, Ginther OJ.The eminent event in follicle selection during a follicular wave in monovular species is diameter deviation, wherein one follicle continues to grow (developing dominant) and other follicles (subordinates) begin to regress. In cattle, the IGF system, oestradiol and LH receptors are involved in the intrafollicular events initiating deviation as indicated by the following: (1) concentrations of free IGF-I and oestradiol in the follicular fluid and number of LH receptors in the follicular wall increase more dramatically in the future dominant follicle than in the future subordinate follicles befor...
Signaling through the small G-protein Cdc42 is involved in insulin-like growth factor-I resistance in aging articular chondrocytes.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    June 17, 2006   Volume 24, Issue 8 1765-1772 doi: 10.1002/jor.20185
Fortier LA, Miller BJ.During aging, chondrocytes become unresponsive to insulin-like growth factor-I (IGF-I). This study examined the role of Cdc42 (cell-division-cycle 42) in IGF-I signaling during aging. Experiments were performed using cartilage and chondrocytes isolated from horses ages 1 day-25 years. Northern analysis was used to examine expression of the small GTPases Cdc42, Rac, and RhoA. Western analysis was utilized to assess total Cdc42 (GTP + GDP-bound); active, GTP-Cdc42 was assessed using a pulldown assay with Western analysis. GTP-Cdc42 was also measured following IGF-I treatment. Gene expression for...
Expression of insulin-like growth factor binding proteins in healing tendon lesions.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    January 26, 2006   Volume 24, Issue 2 183-192 doi: 10.1002/jor.20000
Dahlgren LA, Mohammed HO, Nixon AJ.he treatment of overuse tendon injuries with exogenous growth factors such as insulin-like growth factor-I (IGF-I) may facilitate an improved return to sustained athletic function. The biological effects of IGF-I are exerted under the control of a complex of IGF receptors, binding proteins, and proteases. This IGF system includes a family of six structurally related high-affinity IGF binding proteins (IGFBPs) that protect IGF-I from local proteases and restrict access of IGF-I to its receptor. This study describes the expression of the IGFBPs in flexor tendon after acute injury and during heal...
Leptin secretion in horses: effects of dexamethasone, gender, and testosterone.
Domestic animal endocrinology    November 8, 2005   Volume 31, Issue 2 197-210 doi: 10.1016/j.domaniend.2005.10.006
Cartmill JA, Thompson DL, Del Vecchio RP, Storer WA, Crowley JC.Five experiments were performed to evaluate the effects of dexamethasone (DEX), gender, and testosterone on plasma leptin concentrations in horses. In experiment 1, plasma leptin, insulin, glucose, and IGF-1 concentrations were increased (P < 0.01) in stallions following five daily injections of DEX (125 microg/kg BW). In experiment 2, leptin concentrations increased (P < 0.01) in mares, geldings, and stallions following a single injection of DEX, and the response was greater (P < 0.01) in mares and geldings than in stallions. The gender effect was confounded by differences in body co...
Expression of inhibins, activins, insulin-like growth factor-I and steroidogenic enzymes in the equine placenta.
Domestic animal endocrinology    September 29, 2005   Volume 31, Issue 1 19-34 doi: 10.1016/j.domaniend.2005.09.005
Arai KY, Tanaka Y, Taniyama H, Tsunoda N, Nambo Y, Nagamine N, Watanabe G, Taya K.In this study, the expression patterns of inhibins, activins, insulin-like growth factor-I (IGF-I) and steroidogenic enzymes in equine placentae recovered during the latter two-thirds of gestation were examined. Concentrations of inhibin A and inhibin pro-alphaC in endometrial and fetal placental tissue homogenates were very low during the period examined, whereas these tissues contained high concentrations of activin A. In both maternal endometrial and fetal placental tissues, activin A levels decreased as pregnancy progressed. Expression of inhibin alpha-subunit was not observed in the place...