Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Müllerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism.

PURPOSE: In cryptorchidism, germ cell development failure presents from infancy and may be reflected by altered hormonal levels produced by Sertoli cells. Our object was to assess for associations between serum hormone levels and testicular histopathology in cryptorchidism with an infertility risk according to the pretreatment undescended testicular positions. MATERIALS AND METHODS: Prepubertal cryptorchid boys aged 7-91 (median 20) months who underwent orchidopexy between 2014 and 2019 were included (122 unilateral [median 19 months {range 7-91}], 23 bilateral [24 months {11-81}]). We evaluated the pretreatment testicular position and size; serum hormone levels; and the mean number of germ cells per tubule transverse section (G/T). We also performed a subgroup analysis of boys aged ≤24 months at orchidopexy. RESULTS: Serum inhibin B levels and G/T were significantly lower in bilateral than in unilateral cryptorchid boys (median 96 [range 46-197] pg/ml vs 125 [21-354] pg/ml, p=0.026; 0.20 [0-2.59] vs 0.65 [0-4.55], p <0.001, respectively). Inhibin B/follicle-stimulating hormones (FSH) and anti-Müllerian hormone (AMH)/FSH ratios were positively correlated with G/T in bilateral cryptorchid boys aged ≤24 months (12, p=0.008 and p=0.019, respectively). Low inhibin B/FSH and AMH/FSH ratios and high FSH were predictors of impaired G/T as per receiver operating characteristic curves (p=0.019, p=0.004 and p=0.004, respectively), whereas in unilateral cryptorchid boys aged ≤24 months, serum hormone levels and G/T did not differ with the pretreatment testicular positions. CONCLUSIONS: In bilateral cryptorchid boys aged ≤24 months at orchidopexy, low inhibin B/FSH and AMH/FSH ratios may reflect impaired G/T and future infertility risk.

Predictive value of the second-trimester fibronectin concentration for severe preeclampsia: A prospective nested case-control study in China.

AIM: To evaluate the value of the second-trimester fibronectin concentration, alone and in combination with other markers (e.g., mean arterial pressure, inhibin A), in the identification of women who subsequently develop severe preeclampsia. METHODS: For this prospective nested case-control study, serum from pregnant women (gestational age 15-22 weeks) who underwent routine Down syndrome screening was analyzed. The women were tracked to delivery and assigned to the severe preeclampsia or control group, according to whether they developed severe preeclampsia. Each woman who later developed severe preeclampsia was paired with five healthy women with pregnancies of similar gestational age (± 1 week). Fibronectin, inhibin A, human chorionic gonadotropin, placental growth factor, cysteine, and homocysteine concentrations were measured in 44 cases in the severe preeclampsia group and 220 cases in the control group. The body mass index and mean arterial pressure were calculated. All results were compared between the two groups. Logistic regression analysis and receiver operating characteristic curve construction were conducted for markers differing significantly between two groups. RESULTS: The second-trimester fibronectin value was positively correlated with severe preeclampsia and predicted 67.7% of severe preeclampsia cases. The combination of fibronectin, inhibin A, and mean arterial pressure predicted 76.7% of severe preeclampsia cases; predictive values for combinations of fibronectin with mean arterial pressure or inhibin A were 75.4% and 74.6%, respectively. Combination with these other markers increased the predictive value of fibronectin. In addition, fibronectin was more powerful for the late severe preeclampsia and severe preeclampsia without fetal growth restriction subgroups. CONCLUSIONS: The second-trimester fibronectin concentration can be used to predict severe preeclampsia.

Fertility Potential is Impaired in Boys with Bilateral Ascending Testes.

PURPOSE: Ascending testes have been documented to be descended in the scrotum within the first year of life and then reascended. The aim of this study was to investigate to what extent the fertility potential was impaired in boys with such testes compared to the fertility potential of boys with late referral congenital cryptorchidism. MATERIALS AND METHODS: A total of 153 consecutive boys underwent bilateral orchiopexy at age 2 to 7 years (median 3.9) between 2011 and 2018. Of the patients 67 were diagnosed with bilateral ascended testes and 86 with late referral bilateral congenital cryptorchidism. We assessed serum levels of inhibin B and gonadotropins and histological parameters, number of germ cells per tubule cross-section and number of type A dark (Ad) spermatogonia per tubule cross-section. All values were compared to our normal material. RESULTS: Number of germ cells per tubule cross-section of boys with ascended testes (median 0.50, range 0 to 2.29) was not significantly higher compared to boys with congenital cryptorchidism (median 0.37, range 0 to 2.57; p=0.11). Mean number of germ cells per tubule cross-section was below normal range in 40 boys with ascending testes (60%) vs 57 boys with late referral congenital cryptorchidism (66%, p=0.40). Biopsies absent of Ad spermatogonia were noted in 31% of boys with ascending testes (21 of 67) vs 34% of boys with congenital cryptorchidism (29 of 86, p=0.76). Serum levels of inhibin B and gonadotropins did not differ between the 2 groups. CONCLUSIONS: The fertility potential of boys with bilateral ascended testes was impaired to almost the same level as that of boys with bilateral congenital cryptorchidism and should therefore be surgically corrected as soon as the diagnosis of ascended testes is settled.

Sex Cord Tumour with Annular Tubules-An Unusual Case of Abdominal Pain.

BACKGROUND: Ovarian sex cord tumours with annular tubules (SCTAT) are a very rare type of neoplasm and account for 14% of all sex cord tumours. This tumour was first described in 1970 with histopathology characterized by the presence of both complex and simple annular tubules. The tumour may show features of either granulosa cell tumours or Sertoli cell tumours and differentiation into either type can occur. CASE: We report an interesting case of SCTAT in a 60-year-old woman who had a primary diagnosis of granulosa cell tumour. Seven years later she experienced a recurrence. Following excision and review of all pathology, the patient was found to have a SCTAT in both the recurrence and the primary tumour. CONCLUSION: SCTAT is a slow-growing tumour that occasionally exhibits malignant behaviour with metastatic potential, albeit many years following initial diagnosis. SCTAT should be included in the differential diagnosis of sex cord tumours.

[The multitasking Sertoli cell]. / Die Multitasking-Sertoli-Zelle.

Sertoli cells (SCs) play a central role in the development of the male genital organs and are absolutely necessary in the adult testis for the maintenance of a normal spermatogenesis. They form the blood-testis barrier, which is a physical barrier between the blood vessels and the seminiferous tubules. Tight junctions between the cell membranes of adjacent SCs divide the seminiferous tubule in a basal compartment (in contact with blood and lymph) and an adluminal compartment (isolated from blood and lymph).The SCs produce more than 60 proteins, of which the most important are hormones. The anti-Müllerian hormone inhibits the development of the female Müllerian ducts in the male embryo. Inhibin inhibits the production of follicle-stimulating hormone (FSH). Activin is an antagonist of inhibin and follistatin inhibits the effect of activin. Furthermore, diverse growth factors are produced, which have auto- and paracrine effects. Androgen-binding protein makes the androgen less lipophilic and becomes more concentrated within the luminal fluid of the seminiferous tubules thus enabling spermatogenesis. Ferritin is necessary for the transport of iron to the rapidly growing germ cells.SCs selectively and rapidly eliminate apoptotic residua of spermatids through phagocytosis. Moreover, as shown in animal experiments, these cells are also able to phagocytize and kill bacteria.Sertoli cell tumors are characterized by a broad spectrum of diversity ranging from highly differentiated adenocarcinoma-like types to completely undifferentiated spindled cell variants.

Sexual dimorphism in postnatal gonadotrophin levels in infancy reflects diverse maturation of the ovarian and testicular hormone synthesis.

BACKGROUND: The postnatal gonadotrophin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotrophin levels are higher than in PT boys. OBJECTIVE: To evaluate how gonadal maturation contributes to the sex differences in FSH and LH. DESIGN: Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from 1 week (D7) to 6 months of age (M1-M6). Analyses were also carried out according to postmenstrual (PM) age in PT infants. METHODS: Urinary LH, FSH, oestradiol (E2), testosterone (T) and serum inhibin B (InhB) levels. RESULTS: High gonadotrophin levels in PT girls abruptly decreased (P < .001) by M2, corresponding to a PM age of 38-42 weeks, and LH levels fell below the levels found in boys. This decrease was parallel to a steep increase in E2 levels (P < .001), and, from M4 to M6, LH and E2 correlated positively in PT girls (P < .01). T levels in PT boys increased earlier than E2 levels in PT girls. In addition, InhB levels were high in PT boys already at D7, in contrast to low InhB in PT girls. InhB and FSH correlated negatively in the whole group (P < .001). CONCLUSIONS: Ovarian hormone synthesis is immature and incapable of responding to gonadotrophin stimulus before 38-42 PM weeks in PT girls, which may explain their highly elevated FSH and LH levels. The higher InhB levels in boys compared to girls may explain sexual dimorphism in FSH levels.

Serum inhibin B values in boys with unilateral vanished testis or unilateral cryptorchidism.

PURPOSE: Boys with cryptorchidism have overall increased gonadotropin and decreased serum inhibin B levels compared to normal. Serum inhibin B levels, produced by Sertoli cells, may reflect the state of germinative epithelium in cryptorchid testes. We evaluated whether serum inhibin B levels differed between boys with unilateral vanished testis and those with unilateral cryptorchidism. MATERIALS AND METHODS: Blood samples from 297 boys 1.5 to 5 years old were included, of whom 222 had unilateral cryptorchidism, 29 had unilateral vanished testis and 46 had undergone unilateral orchiopexy 1 year previously. Serum inhibin B levels were measured using a commercially available ELISA kit and were compared to normal range. RESULTS: Serum inhibin B levels in boys with unilateral vanished testis were not different from those with unilateral cryptorchidism. Serum inhibin B values were above the normal median in 43% of boys previously operated on for unilateral cryptorchidism, compared to 17% at surgery (p = 0.0003). The percentage of patients with inhibin B levels below normal range was 14% in those with unilateral vanished testis, 23% in those with unilateral cryptorchidism and 11% in those who had undergone orchiopexy 1 year previously for unilateral cryptorchidism. The percentage of boys with inhibin B levels above normal median was 24% in those with unilateral vanished testis, 17% in those with unilateral cryptorchidism and 43% in those who had undergone orchiopexy. However, in boys with a vanished testis the frequency of serum inhibin B above normal median was only 5% before age 1.5 years, after which the rate was 67% (p = 0.0022). CONCLUSIONS: Our findings may reflect the development of contralateral testicular hypertrophy in boys with unilateral vanished testis. The initial low inhibin B values may be explained by impaired total number of Sertoli cells. Serum inhibin B values also indicated that in 6-month to 5-year-old boys with cryptorchidism orchiopexy was beneficial for the germinative epithelium.

Performance of the two new fully automated anti-Müllerian hormone immunoassays compared with the clinical standard assay.

STUDY QUESTION: How do the two new fully automated anti-Müllerian hormone (AMH) assays released in September 2014 by two different diagnostic companies perform compared with the clinical standard assay, namely the AMH Gen II enzyme-linked immunosorbent assay (ELISA)? SUMMARY ANSWER: Both fully automated AMH assays perform in a nearly identical fashion compared with the AMH Gen II assay, with a higher analytical sensitivity. WHAT IS KNOWN ALREADY: Owing to the lack of standardization, the results of AMH ELISA assays are sometimes difficult to compare. The BCI AMH Gen II assay became the clinical reference assay over the last few years. Two newly developed fully automated, highly sensitive AMH immunoassays, based on the AMH Gen II antibody composition have become available since September 2014. STUDY DESIGN, SIZE, DURATION: Previously characterized serum samples from 155 women were used to measure AMH with the three immunoassays, focusing on the aspect of predicting ovarian reserve. PARTICIPANTS/MATERIALS, SETTING, METHODS: Samples from 94 women with an unfilled desire for a child diagnosed as infertile/subfertile, 29 samples women with polycystic ovary syndrome and 32 women approaching menopause were included to the study. The precision and the linearity in dilutions of the two new AMH assays were determined and the assay results were compared with the clinical reference (the modified version of the BCI AMH Gen II assay) and to the antral follicle counts of the study participants. Cutoff values for the discrimination between each of two predefined groups were calculated using receiver operating characteristic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The performance evaluation of the fully automated AMH assays resulted in a within-run and intermediate precision of 0.9-1.9% and 2.5-6.5% with the one and 0.9-3.6% or 4.4-10.7% with the other immunoassay, respectively. Pearson's coefficient of correlation was 0.991 for the method comparison between both assays with a bias of 0.003 ng/ml and a slope of 0.97. The discrimination of the new immunoassays between subfertile women and women approaching menopause was significantly better compared with the BCI Gen II assay (87.5 versus 68.8%, P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Owing to the low number of study subjects in each group, the results have to be confirmed in further studies. WIDER IMPLICATIONS OF THE FINDINGS: The findings of the study are in good agreement with studies that used the Ultra Sensitivite AMH and the pico AMH ELISA assays. The application of AMH measurement onto an automated immunoassay platform is a major step forward, allowing health care providers rapid access to the AMH result and facilitating the adoption of AMH measurement into daily clinical practice. STUDY FUNDING/COMPETING INTERESTS: We declare no financial relationships or competing interests.

Maternal Serum Activin A, Inhibin A and Follistatin-Related Proteins across Preeclampsia: Insights into Their Role in Pathogenesis and Prediction.

BACKGROUND: Within the endocrine-paracrine signalling network at the maternal-foetal interface, the activin-inhibin-follistatin system modulates extravillous trophoblast invasion, suggesting a potential role in preeclampsia pathogenesis. This study aimed to compile the evidence published in the last decade regarding the variation in maternal serum activins, inhibin- and follistatin-related proteins in preeclamptic pregnancies compared to healthy pregnancies, and to discuss their role in predicting and understanding the pathophysiology of preeclampsia. MATERIAL AND METHODS: A scoping review was conducted in MEDLINE, EMBASE and LILACS databases to identify studies published within the last ten years (2012-2022). RESULTS: Thirty studies were included. None of the studies addressed maternal serum changes of isoforms different from activin A, inhibin A, follistatin, and follistatin-like 3. Sixteen studies evaluated the potential of these isoforms in predicting preeclampsia through the area under the curve from a receiver operating characteristic curve. CONCLUSIONS: In preeclampsia, inhibin A is upregulated in all trimesters, whereas activin A increases exclusively in the late second and third trimesters. Serum follistatin levels are reduced in women with preeclampsia during the late second and third trimesters. However, changes in follistatin-like 3 remain inconclusive. Inhibin A and activin A can potentially serve as biomarkers of early-onset preeclampsia based on the outcomes of the receiver operating characteristic curve analysis. Further investigations are encouraged to explore the feasibility of quantifying maternal serum levels of activin A and inhibin A as a clinical tool in early preeclampsia prediction.

Efficacy of cyclin-dependent kinase 4/6 inhibitors in combination with hormonal therapy in patients with recurrent granulosa cell tumor of the ovary: A case series.

Cyclin-dependent kinase inhibitors are approved in combination with hormonal therapy for treatment of hormone receptor expressing breast cancers. Activity in hormone receptor expressing gynecologic cancers has been postulated. Granulosa cell tumor of the ovary is one such cancer, which is relatively resistant to traditional cytotoxic chemotherapy. We report a case series of 7 heavily pre-treated patients with recurrent granulosa cell tumor of the ovary with a cyclin-dependent kinase inhibitor in combination with hormonal therapy, with 3 patients demonstrating partial response and 2 with stable disease. As of the data cutoff, 3 patients remained on treatment and 5 were alive, with true medians for duration of treatment and overall survival not reached (medians at data cutoff of 64 weeks and 62 months respectively). The treatment was generally well tolerated, with 1 patient choosing to discontinue treatment due to grade 3 fatigue. This regimen represents a possible option in the treatment of granulosa cell tumor of the ovary, warranting further prospective study for this unmet need in this indolent disease which often requires many lines of treatment.

Primary retroperitoneal extraovarian granulosa cell tumor.

Extraovarian granulosa cell tumors (GCTs) develop from ectopic gonadal tissue situated along the embryonal route of the genital ridge. Primary retroperitoneal tumors are extremely rare, with an incidence of 02% -06% and 80-85% probability of malignancy. Only eight such case reports have been published previously. We herein, report a rare case of extraovarian retroperitoneal GCT in a 55-year-old woman who presented with intermittent left lumbar region pain of one-year duration. She had a history of hysterectomy and bilateral salpingo-oophorectomy 8 years ago for uterine leiomyoma. Laparotomy revealed a retroperitoneal mass measuring 8cm x 10cm x 20cm in size, solid cystic with areas of necrosis and hemorrhage. The gross features, classical histopathology, and positive immunostaining of the retroperitoneal mass with inhibin, calretinin, PR, WT1 and immunonegativity for EMA were characteristic of adult-type GCT. Excluding any previous history of primary ovarian GCT in this patient, a de-novo retroperitoneal diagnosis was established.

Serum and urine profiles of TGF-ß superfamily members in reproductive aged women.

BACKGROUND: TGF-ß superfamily members are important biomarkers of reproductive health in women desiring fertility and during pregnancy. TGF-ß proteins derived from the ovary and/or placenta have been detected in serum in women, but there have been very few attempts to measure them non-invasively, such as in urinary samples, and to compare them to serum concentrations. METHODS: We measured inhibin A, inhibin B, total inhibin, AMH, activin A, activin B, activin AB, follistatin, the GDF-9/BMP-15 complex, and GDF-15 in paired serum and urine samples from healthy reproductive aged women and in pregnant (second trimester) women. RESULTS: We detected all hormones in serum in both pregnant and non-pregnant women. Inhibin A, total inhibin, activin A, activin AB, follistatin, and GDF-15 were significantly higher in pregnant than in non-pregnant women. GDF-15 was the only hormone consistently detected in urine. We also measured, for the first time, the GDF-9/BMP-15 functional heterodimer and the GDF-15 protein harboring the H202D polymorphism. CONCLUSIONS: We report the successful measurement of the GDF-9/BMP-15 heterodimer (its native form) in serum and the ability to measure GDF-15 non-invasively, in urinary samples. This novel GDF-15 assay also captures the antigen in the presence of a common genetic variant.

Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report.

BACKGROUND: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene. CASE PRESENTATION: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation. CONCLUSION: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations.

Molecular characterization and expression pattern of inhibin α and ßb in Chinese tongue sole (Cynoglossus semilaevis).

Inhibin plays important roles in vertebrate reproduction and development. In this study, we have cloned two genes encoding inhibin subunits, inhα and ihnßb, in Chinese tongue sole. inhα consists of 1032 bp, encoding a 343 amino-acid protein. inhßb is composed of 1275 bp, encoding a 424 amino-acid protein. Phylogenetic tree analysis indicated that INHα and INHßB were independently evolved. qPCR showed that inhα expression of in male testis was higher than that in ovary and pseudomale testis, while the expression of inhßb in ovary was higher than that in male and pseudomale testis. During gonadal developmental stages, inhα expression reached highest at 120 days post hatching (dph) both in ovary and testis, then showed decline in ovary but it was first decreased and then increased in the testis. Similarly, inhßb expression in ovary was low at 50-80 dph. At 120 dph, its expression was significantly increased to the peak level, and then gradually decreased. inhßb expression in testis maintained at a low level. During the embryonic developmental stages, inhα displayed the highest expression at 32-cell stage, whereas inhßb reached the highest expression at blastula stages. In situ hybridization data showed that both of inhα and inhßb were detected in oocytes of all stages. In male testis, inhα and inhßb was localized in spermatogonia, spermatocytes, spermatozoa, sertoli and leydig cells. In pseudomale testis, inhα showed the similar pattern in male testis, while the inhßb was detected in spermatocytes and spermatozoa. These data suggested that inhα may participate the spermatogenesis and oogenesis of Chinese tongue sole, while inhßb might predominantly function in oogenesis.

An Unusual Cause of Secondary Amenorrhea in an Adolescent: Expanding the Differential.

Secondary amenorrhea is not uncommon in the adolescent female population. There are multiple etiologies to consider, and a comprehensive evaluation is often pursued. Sometimes, however, despite a thorough workup, the diagnosis remains unclear. Here, we report an unusual cause of secondary amenorrhea in a 15-year-old girl. Our patient presented with secondary amenorrhea after a 4-year history of regular menstrual cycles. Her evaluation was notable for very low FSH and low estradiol but normal LH; pregnancy, adrenal, thyroid, prolactin studies, and brain magnetic resonance imaging scan did not reveal a cause of her amenorrhea. Her transabdominal ultrasound showed an enlarged right ovary, initially suggestive of a hemorrhagic cyst. Inhibin A and B were measured because of the persistently low FSH; these were found to be very elevated, concerning for an inhibin-producing tumor. The patient had surgical removal of her right ovary; pathology revealed a juvenile granulosa-cell tumor. Postoperatively, the patient had normalization of serum inhibin A and B and resumption of normal menstrual cycles. This report illustrates that careful consideration of laboratory findings and other studies is essential for correctly identifying the underlying cause of secondary amenorrhea, particularly when the results are not consistent with common causes of this condition.

Inhibins regulate peripheral regulatory T cell induction through modulation of dendritic cell function.

We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed-type hypersensitivity responses. Here, we investigated the role of inhibins in peripheral regulatory T cell (Treg) induction in vitro and in vivo. Inhibin deficient (Inhα-/-) mice showed an increased percentage of peripherally induced Tregs in colonic lamina propria and mesenteric lymph nodes, compared to Inhα+/+ mice, which correlated with increased expression of PD-L1 in CD103+ and CD8α+ DCs. Lipopolysaccharide-stimulated bone marrow-derived and ex vivo spleen- and lymph node-purified CD11c+ Inhα-/- DCs induced higher Tregs in vitro. Moreover, in vivo anti-DEC205-ovalbumin (OVA) DC targeting of mice with adoptively transferred OVA-specific T cells showed enhanced induced peripheral Treg conversion in Inhα-/- mice. These data identify inhibins as key regulators of peripheral T cell tolerance.

The transforming growth factor ß superfamily as possible biomarkers of preeclampsia: a comprehensive review.

The etiology of preeclampsia - an abnormal placentation-mediated disease - is not fully understood; and there are very few biomarkers with which to predict and diagnose it. Early prediction and diagnosis of this pathology can lead to a significant improvement in maternal and perinatal outcomes. Since members of the transforming growth factor ß superfamily influence placentation, and are released from the placenta into the maternal circulatory system, several studies have investigated the involvement of these cytokines in preeclampsia and the possibility of using their serum levels as biomarkers of the disease. In this review, we have summarized the reported relationships between the levels of this superfamily of cytokines and preeclampsia. The available information indicates that altered levels of some of these cytokines are involved in the pathogenesis and pathophysiology of preeclampsia, suggesting their likelihood of serving as predictive and diagnostic biomarkers of the disease.

Pituitary-testicular Axis Dysfunction in Methimazole-induced Hypothyroidism in Rats.

INTRODUCTION: Thyroid hormones play a major role in the regulation of testicular maturation and growth and in the control of Sertoli and Leydig cell functions in adulthood. When naturally occurring, hypothyroidism causes male hypogonadotropic hypogonadism and Sertoli cell function disorders, but when iatrogenic and methimazole-induced its influence on the pituitary-testicular axis function with respect to Sertoli cells is poorly known. MATERIAL AND METHODS: Male adult Wistar rats (n = 14) were divided into two groups: E - taking methimazole orally for 60 days, and C - control animals. After 60 d, the concentrations in serum of testosterone, follicle-stimulating and luteinising hormones, and inhibins A and B were measured. Testicles were examined morphologically: the apoptotic Sertoli cell percentage (ASC%) and number of these cells functional per tubular mm2 (FSCN/Tmm2) were calculated. RESULTS: In group E, inhibin A was higher while inhibin B was lower than in group C. ASC% was higher and FSCN/Tmm2 lower in group E than in group C. CONCLUSION: A specific modulation of Sertoli cell function in the course of methimazole-induced hypothyroidism leads to a simultaneous concentration increase in inhibin A and decrease in B. Inhibin A might share responsibility for pituitary-testicular axis dysfunction and hypogonadotropic hypogonadism in this model of hypothyroidism.

Primary retroperitoneal extraovarian granulosa cell tumor

Extraovarian granulosa cell tumors (GCTs) develop from ectopic gonadal tissue situated along the embryonal route of the genital ridge. Primary retroperitoneal tumors are extremely rare, with an incidence of 02% -06% and 80-85% probability of malignancy. Only eight such case reports have been published previously. We herein, report a rare case of extraovarian retroperitoneal GCT in a 55-year-old woman who presented with intermittent left lumbar region pain of one-year duration. She had a history of hysterectomy and bilateral salpingo-oophorectomy 8 years ago for uterine leiomyoma. Laparotomy revealed a retroperitoneal mass measuring 8cm x 10cm x 20cm in size, solid cystic with areas of necrosis and hemorrhage. The gross features, classical histopathology, and positive immunostaining of the retroperitoneal mass with inhibin, calretinin, PR, WT1 and immunonegativity for EMA were characteristic of adult-type GCT. Excluding any previous history of primary ovarian GCT in this patient, a de-novo retroperitoneal diagnosis was established.

Neonatal exposure to 17α-ethynyl estradiol (EE) disrupts follicle development and reproductive hormone profiles in female rats.

Toxic effects induced by exposure to endocrine-disrupting chemicals during fetal and neonatal periods can be irreversible and exert effects throughout an animal's entire life. Our previous study showed that neonatal exposure to 17α-ethynyl estradiol (EE) induced irregular estrous cycle in adults. To uncover the reason for the delayed effect after neonatal exposure to EE, reproductive parameters including ovarian weight, ovarian steroidogenesis, and hormonal profiles were investigated in developing female rats. Ovarian weight decreased at postnatal days (PND) 14 and 21 after neonatal exposure to EE. Ovarian histology at PND21 showed that the ratio of follicles with a diameter >300µm decreased and the ratio of follicles with a diameter of 100-150µm increased in EE-treated ovaries, indicating that neonatal exposure to EE retarded follicular development. Moreover, the expression of P450arom increased at PND14 and the expressions of inhibin/activin subunits ßA and ßB decreased at PND21 in EE-treated ovaries. Consistent with the expression of P450arom, circulating levels of 17ß-estradiol increased at PND14 in EE-treated animals. Furthermore, the circulating levels of luteinizing hormone (LH) also increased at PND14 in the treated animals. Although the expression of Kiss1 did not change in the anteroventral periventricular nucleus (AVPV) of the hypothalamus between controls and EE-treated rats, the expression of Kiss1 was reduced in the arcuate nucleus (ARC) of the hypothalamus at PND14. Based upon those results, we suggest that neonatal exposure to EE disrupted the system regulating the interactions between the reproductive hormones and follicle development in pre-pubertal rats, which may result in reproduction dysfunction in adulthood.