Role Of Inhibin Research Articles

Role of Inhibin B, AMH, GnRHa Test and HCG Stimulation Test to Distinguish Isolated Hypogonadotropic Hypogonadism (IHH) from Constitutional Delay in Growth and Puberty (CDGP).

This study aimed to distinguish isolated hypogonadotropic hypogonadism (IHH) from constitutional delay in growth and puberty (CDGP) by various hormonal tests in both sexes. Boys with testicular volume (TV) <4 ml (14-18 years) and girls with breast B1 stage (13-18 years) were enrolled in this study. A detailed history, clinical examination and hormonal analysis including basal luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Mullerian hormone (AMH), testosterone (boys), oestradiol (girls), triptorelin stimulation test and 3-day human chorionic gonadotropin (HCG) stimulation test (boys) were performed. All patients were followed for 1.5 years or till 18 years of age. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-offs with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for various hormones to distinguish IHH from CDGP. Of 34 children (male: 22 and female: 12), CDGP and IHH were diagnosed in 21 and 13 children, respectively. 4 hours post-triptorelin LH had the highest sensitivity (100%) and specificity (100%) for identifying IHH in both sexes. Basal inhibin B had good sensitivity (male: 85.7% and female: 83.8%) and specificity (male: 93.3% and female: 100%) for diagnosing IHH. 24 hours post-triptorelin testosterone (<34.5 ng/dl), day 4 post-HCG testosterone (<99.7 ng/dl) and 24 hours post-triptorelin oestradiol (<31.63 pg/ml) had reasonable sensitivity and specificity for identifying IHH. Basal LH, FSH and AMH were poor discriminators for IHH in both sexes. The best indicator was post-triptorelin 4-hour LH followed by inhibin B, which had a reasonable diagnostic utility to distinguish IHH from CDGP in both boys and girls.

Hypoxia-induced inhibin promotes tumor growth and vascular permeability in ovarian cancers

Hypoxia, a driver of tumor growth and metastasis, regulates angiogenic pathways that are targets for vessel normalization and ovarian cancer management. However, toxicities and resistance to anti-angiogenics can limit their use making identification of new targets vital. Inhibin, a heteromeric TGFβ ligand, is a contextual regulator of tumor progression acting as an early tumor suppressor, yet also an established biomarker for ovarian cancers. Here, we find that hypoxia increases inhibin levels in ovarian cancer cell lines, xenograft tumors, and patients. Inhibin is regulated primarily through HIF-1, shifting the balance under hypoxia from activins to inhibins. Hypoxia regulated inhibin promotes tumor growth, endothelial cell invasion and permeability. Targeting inhibin in vivo through knockdown and anti-inhibin strategies robustly reduces permeability in vivo and alters the balance of pro and anti-angiogenic mechanisms resulting in vascular normalization. Mechanistically, inhibin regulates permeability by increasing VE-cadherin internalization via ACVRL1 and CD105, a receptor complex that we find to be stabilized directly by inhibin. Our findings demonstrate direct roles for inhibins in vascular normalization via TGF-β receptors providing new insights into the therapeutic significance of inhibins as a strategy to normalize the tumor vasculature in ovarian cancer.

Inhibin Inactivation in Female Mice Leads to Elevated FSH Levels, Ovarian Overstimulation, and Pregnancy Loss.

Inhibins are members of the transforming growth factor-β family, composed of a common α-subunit disulfide-linked to 1 of 2 β-subunits (βA in inhibin A or βB in inhibin B). Gonadal-derived inhibin A and B act in an endocrine manner to suppress the synthesis of follicle-stimulating hormone (FSH) by pituitary gonadotrope cells. Roles for inhibins beyond the pituitary, however, have proven difficult to delineate because deletion of the inhibin α-subunit gene (Inha) results in unconstrained expression of activin A and activin B (homodimers of inhibin β-subunits), which contribute to gonadal tumorigenesis and lethal cachectic wasting. Here, we generated mice with a single point mutation (Arg233Ala) in Inha that prevents proteolytic processing and the formation of bioactive inhibin. In vitro, this mutation blocked inhibin maturation and bioactivity, without perturbing activin production. Serum FSH levels were elevated 2- to 3-fold in InhaR233A/R233A mice due to the loss of negative feedback from inhibins, but no pathological increase in circulating activins was observed. While inactivation of inhibin A and B had no discernible effect on male reproduction, female InhaR233A/R233A mice had increased FSH-dependent follicle development and enhanced natural ovulation rates. Nevertheless, inhibin inactivation resulted in significant embryo-fetal resorptions and severe subfertility and was associated with disrupted maternal ovarian function. Intriguingly, heterozygous Inha+/R233A females had significantly enhanced fecundity, relative to wild-type littermates. These studies have revealed novel effects of inhibins in the establishment and maintenance of pregnancy and demonstrated that partial inactivation of inhibin A/B is an attractive approach for enhancing female fertility.

Role of inhibin B in detecting recurrence of granulosa cell tumors of the ovary in postmenopausal patients

IntroductionSeveral biomarkers have been proposed for the detection of recurrences in adult-type granulosa cell tumors of the ovary. Here we validate the value of inhibin B in detecting recurrences and...

Inhibin as a reproductive biomarker part 2. Clinical significance of inhibins in reproductive medicine

In the early 2000s, the determination of inhibin levels was used actively for the diagnosis of ovarian tumors, as a diagnostic marker for prenatal screening of Down syndrome, as well as a prognostic marker for ovarian reserve when conducting assisted reproductive technologies. However, to date, inhibin is rarely used as a marker for reproductive function. At the same time, numerous studies of recent years indicate the crucial role of inhibin in folliculogenesis and spermatogenesis, as well as in implantation and placentation. This allows to significantly expand the diagnostic spectrum of inhibin levels in various disorders of the reproductive system of both women and men.

The role of inhibin B in the regulation of spermatogenesis and its clinical significance in male infertility

The article contains a review of domestic and foreign literature on the assessment of the clinical significance of inhibin B in the male factor infertility. Modern scientific evidence is given that inhibin B plays an important role in the regulation of spermatogenesis and can be an independent predictor of early violations of spermatogenesis, damage to the spermatogenic epithelium, as well as an important indicator in the identification of disorders of spermatogenesis.

Inhibin and activin in embryonic and fetal development in ruminants

Inhibin, activin and follistatin are protein hormones with diverse physiological roles. The involvement of inhibin in the regulation of pituitary FSH production and secretion in adult males and non-pregnant females is well established. However, it is unlikely that inhibin plays a similar role in pregnancy in ruminants. Inhibin and activin molecules show a high degree of structural similarity to potent growth and differentiation factors of the transforming growth factor β (TGF-β) superfamily of peptides and their localization in a range of embryonic and fetal tissues indicates that they may thus play a role in development. Furthermore, the demonstration that follistatin is also present in a number of embryonic and fetal tissues and fluids has further implications for the actions of activin to which it binds. The role of inhibin, activin and follistatin in early development has yet to be established since gene knockout experiments have so far proved inconclusive. During mid- and late gestation, high concentrations of inhibin are found in the testes and plasma of male fetuses of sheep and cattle. Inhibin may play a role in regulating pituitary FSH release in late pregnancy, but the very high concentrations of this hormone in ovine fetal testes and in male fetal plasma compared with that observed in the fetal ovary and female fetal plasma has yet to be explained. The recent observation of high concentrations of inhibin, activin and follistatin in amniotic fluid surrounding the fetus is intriguing. Excretion via urine or lung liquid is partly responsible for the presence of these proteins in amniotic fluid. The fetal membranes and the placenta are also possible sources. It remains to be established whether these proteins constitute an inactive pool of secreted hormone or whether they have other actions in this fetal compartment.

The role of bone morphogenetic proteins in ovarian function

Bone morphogenetic proteins (BMPs) represent the largest subclass of growth factors in the transforming growth factor ß (TGF-ß) superfamily. BMPs have proven to be multifunctional regulators of a wide variety of biological processes in numerous types of cell and tissue. The role of inhibins, activins and TGF-ßs (which also belong to the TGF-ß superfamily) in reproduction has been studied extensively over the last 15 years. However, there were no reports on the role of BMPs in the mammalian ovary until 1999 when we reported an intrinsic ovarian BMP system replete with BMP ligands, receptors and novel biological functions. Since this report it has become clear that the BMP system plays an important role in the regulation of ovarian function, evidenced by the ability of BMPs to control granulosa cell proliferation and cytodifferentiation, as well as oocyte development. The physiological relevance of the BMP system has recently been highlighted by the discovery that genetic mutations in the BMP-15 ligand or the BMP type IB receptor lead to critical aberrations in folliculogenesis and ovulation. This review provides a current overview of the rapidly emerging field of the BMP system in mammalian ovarian function.

Therapeutic advantage of genetically engineered Salmonella typhimurium carrying short hairpin RNA against inhibin alpha subunit in cancer treatment

BackgroundIn contrast to its well-known endocrine function, the role of inhibin in cancer development and therapeutic response is unclear. Salmonella, particularly less toxic attenuated Salmonella strains, are used to treat cancer in two ways. First, Salmonella accumulate around tumors, penetrate the cell barrier, and replicate inside the tumors. Second, Salmonella can act as a vehicle for delivering anticancer agents or proapoptotic genes to attack tumors. In this study, we aimed to develop a suitable cancer therapeutic strategy by genetically modifying attenuated Salmonella typhimurium to harbor short hairpin RNA (shRNA) expression plasmids targeting alpha subunit of inhibin (sh-INHA). MethodsWe analyzed the expression of human INHA in normal and cancer cells and tissues. We developed genetically engineered attenuated S. typhimurium harboring sh-INHA (S. typhimurium/sh-INHA) and assessed its cancer therapeutic effects by using cell culture models and syngeneic mouse tumor models. ResultsINHA expression levels were markedly higher in colon cancer and melanoma cells and tissues than in their normal counterparts. Suppression of INHA expression mildly reduced cancer cell survival and induced caspase activation and downregulation of anti-apoptotic Bcl-2 and Bcl-xL expressions. Although the genetically engineered S. typhimurium mildly interfered with the invasion of S. typhimurium into host colon cancer and melanoma cells, S. typhimurium/sh-INHA caused remarkable cytotoxicity in cancer compared with unmodified S. typhimurium or S. typhimurium expressing a control scrambled shRNA (S. typhimurium/sh-Cont). Salmonella typhimurium/sh-INHA-treated mice also showed a significantly inhibited growth of colon cancers and melanomas, with a survival advantage. ConclusionOur results suggest that tumor-targeted therapy using S. typhimurium/sh-INHA may provide a novel cancer treatment option.

Abstract MIP-063: DEFINING NOVEL PARACRINE FUNCTIONS FOR INHIBIN IN OVARIAN CANCER

Abstract BACKGROUND AND SIGNIFICANCE: Inhibins are members of the TGF-β superfamily loss of which in mice results in gonadal tumorigenesis. In humans, Inhibin is elevated in patients across several ovarian cancer subtypes including GCT's, mucinous, clear cell, to lesser extents in high grade serous and also in the stroma of Brenner tumors as reported by several others. Other cancers with elevated Inhibin include prostate and common cancers associated with ascites accumulation such as colon, gastric, and pancreatic. The Type III TGF-β receptor/ Betaglycan is the only high affinity receptor molecule that has been shown to directly bind Inhibin, that does not induce signaling, but is frequently lost in ovarian cancer as reported previously. The overall goal of our studies supported in part by the Rivkin Center for Ovarian Cancer were to 1) define the possible functional consequences of elevated Inhibin in cancers in the absence of Betaglycan, 2) determine whether elevated Inhibin may act as a tumor-promoter via a novel complement of receptors in the absence of Betaglycan and 3) to evaluate the impact of blocking inhibin using a neutralizing antibody on ovarian cancer growth and metastasis. RESULTS: We find that Inhibin (alpha subunit, INHA) is largely expressed by multiple ovarian cancer epithelial cells with Inhibin A significantly elevated in the ascites of ovarian cancer patients. Reducing autocrine production of Inhibin by silencing expression of the alpha subunit in epithelial cells has only modest effects on invitro cancer cell growth, migration and invasion either in the presence or absence of Betaglycan. However, most strikingly, we find that conditioned media from ovarian cancer cells with high Inhibin levels rapidly induce SMAD1/5 activation in a paracrine manner on endothelial cells. We find that both recombinant InhibinA and paracrine Inhibin are activators of endothelial cell signaling and angiogenesis both in -in vitro endothelial differentiation assays and in vivo in mice. Mechanistically, Inhibin utilizes an alternate endothelial receptor complement system, components of which are elevated in the ascites of ovarian cancer patients. Antibodies to both the receptors recognizing Inhibin and Inhibin itself suppress Inhibin induced endothelial cell differentiation and angiogenesis. Additionally, Inhibin is a more robust mediator of angiogenesis as compared to TGF-β or Activin and can synergize with VEGF to stimulate endothelial cell differentiation and angiogenesis. IMPLICATIONS: We have discovered a new mechanism and function for Inhibin that may be relevant for ovarian cancer subtypes and pathologies that present elevated Inhibin. While current anti-angiogenic therapies targeting VEGF show promise for the treatment of advanced ovarian cancers, significant side effects and toxicities exist. Our findings on the paracrine role of Inhibin that is normally at extremely low levels in postmenopausal women suggest that consideration of anti- Inhibin antibodies in conjunction with anti- VEGF therapies may hold promise in the future. These findings will be presented and discussed. Citation Format: Priyanka Singh, Laura Jenkins, Kathleen O'Connell, YingMiao Liu, Andy Nixon, and Mythreye Karthikeyan. DEFINING NOVEL PARACRINE FUNCTIONS FOR INHIBIN IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-063.

Role of Inhibin B in some infertiled women with Polycystic ovary syndrome in Kirkuk city

This Random cross sectional study was conducted to evaluate the effect of Inhibin B in Infertiled women in Kirkuk city which is one indicator to the reproductive ability in polycystic ovary patients ,consider as the disease common in Infertility, also to study the changes in reproductive hormones Follicular stimulating hormone(FSH), Luteinizing hormone (LH) , Estrogen(E2) , prolactin(PRL) Testosterone, Samples were classified into two groups: (38) blood samples from women with primary infertility ,(29) blood samples from women with secondary infertility , compared with (18) samples from women as control group. Blood samples were taken within 2-4 days of menstrual. period of women with their ages ranged from 17-46 years who were visiting the infertility unit in Azady teaching hospital in Kirkuk city. Infertile Samples were divided into two groups: infertiled women with polycystic ovary syndrome and infertiled women for other reasons . the ratio of polycystic ovary syndrome of primary infertility was 65.78% while of secondary was 58.62%. Results indicated that there was a high significant increase in Inhibin B level (p

RNAi-mediated knockdown of inhibin α subunit increased apoptosis in granulosa cells and decreased fertility in mice

Inhibin α (INHα), a member of TGFβ superfamily, is an important modulator of reproductive function that plays a vital role in follicular changes, cell differentiation, oocyte development, and ultimately in mammalian reproduction. However, the role of inhibin α in female fertility and ovarian function remains largely unknown. To define its role in reproduction, transgenic mice of RNAi-INHα that knock down the INHα expression by shRNAi were used. Inhibin α subunit gene was knocked down successfully at both transcriptional and translational levels by RNAi PiggyBac transposon (Pbi) mediated recombinant pshRNA vectors and purified DNA fragments were microinjected into mouse zygotes. Results showed that transgenic female mice were sub-fertile and exhibited 35.28% reduction in litter size in F1 generation relative to wild type. The decreased litter size associated with the reduction in the number of oocytes ovulated after puberty. Serum INHα level was significantly decreased in both 3 and 6 weeks; whereas, FSH was significantly increased in 3 weeks but not in 6 weeks. Furthermore, suppression of INHα expression significantly promoted apoptosis by up-regulating Caspase-3, bcl2, INHβB and GDF9 and down regulated Kitl and TGFβRIII genes both at transcriptional and translational levels. Moreover, it also dramatically reduced the progression of G1 phase of cell cycle and the number of cells in S phase as determined by flow cytometer. These results indicate that suppression of INHα expression in RNAi-transgenic mice leads to disruption of normal ovarian regulatory mechanism and causes reproductive deficiencies by promoting cellular apoptosis, arresting cellular progression and altering hormonal signaling.

Heterologous Expression and Characterization of Indian Sahiwal Cattle (Bos indicus) Alpha Inhibin

Inhibin is a non-steroidal glycoprotein hormone of gonadal origin with major action as negative feedback control of the production of FSH by the anterior pituitary gland. The physiological role of inhibin has led to the development of inhibin immunogens for fertility enhancement in farm animals. It is envisaged that a reduction of endogenous inhibin secretion would increase FSH concentrations and thus offers a potential for increasing the number of ovulatory follicles in the ovary. The present work was carried out to produce recombinant bovine (Indian Sahiwal Cattle; Bos indicus) alpha inhibin (bINH-α) in E. coli by optimizing its expression and purification in biologically active form and to study its immunological characterization. A bacterial protein expression vector system based on the phage T5 promoter was used. The bINH-α encoding gene was successfully cloned and expressed in E. coli and the purified recombinant bINH-α was characterized. Recombinant bINH-α (25 µg mL−1) immunized guinea pigs had a significant increase in litter size compared to the control group. These results indicate a role for recombinant bINH-α as a fecundity vaccine to enhance the ovulation rate and litter size in animals.

Inhibin B and Anti-Müllerian Hormone in Spermatic Vein of Subfertile Men With Varicocele

The pathophysiology of subfertility in men with varicocele remains unclear as well as the role of inhibin B (Inh-B) and anti-Müllerian hormone (AMH). The aim of this study was to evaluate Inh-B and AMH concentrations in the spermatic vein of subfertile men with varicocele. A total of 61 subfertile men with varicocele and 31 fertile controls underwent standard andrological evaluation. All subfertile men underwent varicocelectomy, during which blood samples were obtained from the spermatic vein to evaluate Inh-B and AMH concentrations. Peripheral vein Inh-B concentrations in men with varicocele were lower as compared to controls (52.9 [8.3-136.0) vs 116±9.7 ng/dL, P = .001). There was no difference in AMH concentrations (10.2 [4.4-45.4]) vs 10.4±0.8 pg/dL, P = 0.9). Spermatic vein Inh-B concentrations in men with varicocele were higher compared to those of peripheral vein (87.6±4.4 vs 52.9 [8.3-136.0] ng/dL, P = .001). On the contrary, spermatic vein AMH concentrations were lower compared to those from peripheral vein (8.84 [3.9-47.7] vs 10.2 [4.4-45.4] pg/dL, P = .013). Inh-B constitutes a reliable marker of Sertoli cell function as well as spermatogenesis. On the contrary, the clinical significance of AMH in men with varicocele remains to be elucidated.

Ovarian Follicular Dynamics and Hormonal Changes in Goats during Early Pregnancy

The present study was conducted to characterize follicular development and its hormonal control during early pregnancy in goats. The ovaries of goats (n=8) were scanned daily for follicles (> or = 2 mm in diameter) and corpora lutea by transrectal ultrasound with blood sampling from the jugular vein for monitoring the hormonal changes during the first thirty-five days after mating. During early pregnancy, three (37.5%), four (50%) and one (12.5%) goat showed nine, eight and seven waves of follicular development, respectively. The corpora lutea were detected as early as Day 3.61 ± 0.45 (7.47 ± 0.43 mm) of pregnancy (Day 0=day of mating) and attained their maximal cross-sectional diameter (10.64 ± 0.37 mm) on Day 25.7 ± 0.8 of pregnancy, respectively. A transient rise in FSH levels was temporally associated with the day of follicular wave emergence (up to three days prior to wave emergence). The plasma LH and estradiol levels were negatively correlated with the progesterone concentration. The rise in plasma immunoreactive (ir) inhibin levels was negatively correlated with the FSH concentration and positively correlated with the number of large-sized follicles. Alternatively, the mean plasma ir-inhibin levels showed a noticeable decline with the progression of pregnancy. The present results demonstrated that follicular development during early pregnancy shows a wave-like pattern, with seven to nine waves developing until Day 35 after breeding, and that the number of follicular waves can be predicted by the number of FSH peaks. The current study also demonstrated that the role of inhibin as an FSH regulator is maintained throughout early pregnancy.

Postnatal treatment of human seminal plasma inhibin: gonadotropin and prolactin levels during the onset of puberty in the rat.

Plasma gonadotrophin and prolactin levels, pituitary and accessory sex organ weights were evaluated on day 40 in rats of either sex treated with human seminal plasma (HSP) inhibin on day 7, 15, 21 and 30 postnatally. HSP inhibin suppressed both FSH and LH but without any effect on plasma PRL levels. The weights of pituitary and accessory sex organs were significantly suppressed. These results indicate a role for inhibin in the postnatal gonadotrophin release and a possible direct action on the accessory reproductive organs in the rat.

The Role of Inhibins B and Antimüllerian Hormone for Diagnosis and Follow-up of Granulosa Cell Tumors

The peptide hormones inhibin and antimüllerian hormone (AMH), both produced by the granulosa cells, are potential candidates for diagnosis and follow-up of granulosa cell tumors (GCTs). The objective was to evaluate the usefulness of serum levels of inhibin B and AMH in the diagnosis and follow-up of GCT. The review summarizes and discusses the value and limitations of the laboratory tests of these hormones by investigating the performance characteristics of the serum analyses. A search in PubMed database was accomplished to find articles describing serum inhibin and/or AMH as a diagnostic test or for follow-up of GCT. The literature search included articles published between 1989 and September 2008. The sensitivity of inhibin B and AMH for diagnosing patients with a progressive disease is rather equivalent. Antimüllerian hormone is a more specific serum parameter than inhibin, because inhibin may also increase in some (mucinous) epithelial ovarian tumors. Nowadays, specific and ultrasensitive assays are commercially available as well for inhibin B as for AMH, so that early detection of GCT might be possible. For patients with elevated levels of inhibin B and/or AMH at initial diagnosis of GCT, inhibin B and/or AMH seemed to be reliable markers during follow-up for early detection of residual or recurrent disease. Elevated concentrations of these hormones predict relapse earlier than clinical symptoms, which leads to less morbidity of the patients. In conclusion, inhibin B and AMH are both useful serum markers for diagnosis and especially for follow-up of patients with a GCT. Currently, there is no evidence-based preference for inhibin B or AMH as tumor marker.

Dynamics of circulating concentrations of gonadotropins and ovarian hormones throughout the menstrual cycle in the bonnet monkey: role of inhibin A in the regulation of follicle‐stimulating hormone secretion

In higher primates, increased circulating follicle-stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P(4)) secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern of P(4) secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3+/-2 vs. 27.3+/-3 pg/mL), and a 2- to 3-fold rise in circulating FSH levels by 24 hr (0.20+/-0.02 vs. 0.53+/-0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 microg/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P(4) concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase.

Diagnostic role of inhibins and activins in adverse pregnancy outcomes

Human placenta is an endocrine organ expressing and releasing proteins and steroid hormones. Activins and inhibins, growth factors belonging to the TGF-β superfamily, are also expressed by the placenta. When gestational disease occurs (i.e., hypertension, hypoxia, infection and preterm delivery), placenta takes part in the adaptive response to the adverse condition, and changes its hormonal secretory ability with the aim of modifying the adverse intrauterine environment. The changes in inhibin and activin secretion occurring in pathological pregnancies may be monitored and measured in clinically accessible sites such as maternal serum, amniotic fluid, saliva and urine. In this review, the putative diagnostic role of inhibins and activins in various pathological conditions (i.e., miscarriage and threatened abortion, ectopic pregnancy, trophoblast tumors, Down syndrome, intrauterine growth restriction, hypertensive disorders, and preterm delivery) will be discussed.

Features of follicle-stimulating hormone–stimulated follicles in a sheep model: keys to elucidate embryo failure in assisted reproductive technique cycles

To evaluate the individual functionality of gonadotropin-stimulated preovulatory follicles, for understanding embryo failure in assisted reproductive technique cycles, in a sheep model. Observational, model study. Public research unit. Fifteen adult Manchega ewes. Synchronization of the estrous cycle with intravaginal progestagens and ovarian stimulation with FSH; evaluation of reproductive activity, plasma sampling, ovarian ultrasonography, and ovariectomies. Determination of estrus behavior, plasma and intrafollicular concentrations of E(2) and inhibin A, number and size of ovarian follicles, and developmental competence of oocytes. These results support the usefulness of serial measurements of plasma inhibin A for assessment of follicular growth during the FSH treatment, rather than of E(2) assays commonly used. Functionality of FSH-stimulated preovulatory follicles is clearly disturbed, as confirmed by a negative correlation between follicular size and intrafollicular concentrations of inhibin A and E(2) in preovulatory follicles after individual dissection; moreover, the ability of their oocytes to resume meiosis was diminished. Functionality of follicles in controlled ovarian stimulation (COS), and developmental competence of their oocytes, is disturbed by the high doses of gonadotropin supplied and finally determined by follicular sizes at starting FSH treatment.