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Objective: To assess whether serum inhibin A at 14-20 weeks of gestation is associated with the occurrence of pre-eclampsia., Methods: A retrospective cohort study using propensity score matching was conducted on 11 682 singleton pregnant women with established deliveries at the Obstetrics and Gynecology Hospital of Fudan University between January 2017 and July 2019. We investigated serum inhibin A levels at 14-20 weeks of gestation and calculated the relative risk between inhibin A and pre-eclampsia by multifactorial logistic regression analysis. Smoothed, fitted curves were used to observe the effect of inhibin A in relation to the occurrence of pre-eclampsia., Results: The risk of pre-eclampsia occurrence increased with elevated serum inhibin A. After full adjustment for confounders, the risk ratio for pre-eclampsia in the group of pregnant women with high inhibin A was 2.92 (95% confidence interval [CI] 2.08-4.11) compared with those with normal inhibin A. The results of sensitivity analysis suggested a consistent effect of inhibin A on the risk of pre-eclampsia in different populations., Conclusion: Elevated serum inhibin A at 14-20 weeks of gestation is associated with pre-eclampsia and may provide an early warning signal for pregnancy outcomes associated with pre-eclampsia., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: The effects of novel non-cytotoxic and immunotherapy drugs for cancer treatment on human testicular function have not been studied systematically., Objectives: The present study aimed to characterize effects of non-cytotoxic and immunotherapy drugs in patients with cancers who had not been previously treated with gonadotoxic chemo- or radiotherapy., Materials and Methods: This study involved 34 men, not previously treated with gonadotoxic regimens, in a mixed longitudinal (Cohort 1: 19 men about to start and approximately 1 year on non-cytotoxic and immunotherapy treatment) and cross-sectional (Cohort 2: 15 men already on non-cytotoxic and immunotherapy treatment) study using data modeling to estimate within-person time-course changes in testicular exocrine and endocrine functions. Cohort 1 provided 45 paired semen and blood samples (34 prior to and nine during treatment) and Cohort 2 provided 45 sets of samples (15 pre-treatment, 30 on treatment), including six men in Cohort 2 who had pre-treatment spermatozoa cryostorage prior to the study. Men on non-cytotoxic and immunotherapy treatment had undergone a median of 33.5 months long-term treatment., Results: Spermatozoa output and concentration were reduced by about 50%, with corresponding increases in serum follicle-stimulating hormone and decreases in serum inhibin B. Serum testosterone, luteinizing hormone, and sex hormone-binding globulin were unaffected by non-cytotoxic and immunotherapy treatment., Conclusion: Within limits of the present study of sample size and duration of on-non-cytotoxic and immunotherapy treatment, non-cytotoxic and immunotherapy drugs have a modest effects on testicular exocrine function (sperm production) or its hormonal correlates (follicle-stimulating hormone, inhibin B), with minimal impact on testicular endocrine (testosterone, luteinizing hormone) function., (© 2023 Commonwealth of Australia. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Gonadotropin inhibitory hormone (GnIH) is essential for regulating the reproduction of mammals and inhibiting testicular activities in mice. This study aimed to explore the mechanism of GnIH on spermatogenesis and steroidogenesis by acting through the hypothalamus-pituitary-testis axis of mice. Mice were subcutaneously injected with different doses of GnIH (1 μg/150 μL, 3 μg/150 μL, 6 μg/150 μL, 150 μL saline, twice daily) for 11 days. Subsequently, luteinizing hormone (LH), testosterone (T), and inhibin B (INH B) levels of peripheral blood were determined, and the expression of GnRH synthesis-related genes (GnRH-1, Kiss-1, NPY) and gonadotropin synthesis-related genes (FSH β, LH β, GnRH receptor) in the hypothalamus and pituitary gland were respectively detected. Additionally, the expression of steroidogenesis-related genes/proteins (P450scc, StAR and 3β-HSD) and spermatogenesis-related proteins/genes including LH receptor (LHR), androgen receptor (AR), heat shock factor-2 (HSF-2) and INH B were analyzed using western blot and q-PCR. Results showed that GnIH treatment significantly reduced the concentration of LH in the peripheral blood. Further analysis revealed that GnIH treatment markedly reduced the expression of GnRHImRNA and Kiss-1 mRNA in the hypothalamus, and mRNA levels of FSH β, LH β, and GnRHR genes in the pituitary. We also observed that GnIH treatment significantly decreased T levels and expression of the P450scc, StAR, and 3β-HSD proteins in the testis. Furthermore, GnIH treatment down-regulated LHR, AR proteins, and HSF-2 gene in the testis. Importantly, the INH B concentration of and INH βb mRNA levels significantly declined following GnIH treatment. Additionally, GnIH treatment may induce germ cell apoptosis in the testis of mice. In conclusion, GnIH may suppress spermatogenesis and steroidogenesis by acting through the hypothalamus-pituitary-testis axis in mice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rats are multiparous rodents that have been used extensively in research; however, the low reproductive performance of some rat strains hampers the broader use of rats as a biomedical model. In this study, the possibility of increasing the litter size after natural mating in rats through superovulation using an anti-inhibin monoclonal antibody (AIMA) was examined. In outbred Wistar rats, AIMA increased the number of ovulated oocytes by 1.3-fold. AIMA did not affect fertilization and subsequent embryonic development, resulting in a 1.4-fold increase in litter size and a high pregnancy rate (86%). In contrast, conventional superovulation by eCG/hCG administration decreased the pregnancy rate to 6-40% and did not increase the litter size. In inbred Brown Norway rats, AIMA increased the litter size by 1.2-fold, and the pregnancy rate increased more than twice (86% versus 38% in controls). AIMA also increased the litter size by 1.5-fold in inbred Tokai High Avoiders and Fischer 344 rats. AIMA increased the efficiency of offspring production by 1.5-, 2.7-, 1.4-, and 1.4-fold, respectively, in the four rat strains. Thus, AIMA may consistently improve the reproductive performance through natural mating in rats, which could promote the use of AIMA in biomedical research., (© 2024. The Author(s).)

The objective of the present study was to investigate the potential role of immunization against INH on follicular development, serum reproductive hormone (FSH, E 2 , and P 4 ) concentrations, and reproductive performance in beef cattle. A total of 196 non-lactating female beef cattle (4-5 years old) with identical calving records (3 records) were immunized with 0.5, 1.0, 1.5, or 2.0 mg [(T1, n = 58), (T2, n = 46), (T3, n = 42) and (T4, n = 36), respectively] of the pcISI plasmid. The control (C) group (n = 14) was immunized with 1.0 mL 0.9% saline. At 21d after primary immunization, all beef cattle were boosted with half of the primary immunization dose. On day 10 after primary immunization, the beef cattle immunized with INH DNA vaccine evidently induced anti-INH antibody except for the T1 group. The T3 group had the greatest P/N value peak among all the groups. The anti-INH antibody positive rates in T2, T3 and T4 groups were significantly higher than that in C and T1 groups. RIA results indicated that serum FSH concentration in T2 group increased markedly on day 45 after booster immunization; the E 2 amount in T3 group was significantly increased on day 10 after primary immunization, and the levels of E 2 also improved in T2 and T3 groups after booster immunization; the P 4 concentration in T2 group was significantly improved on day 21 after primary immunization. Ultrasonography results revealed that the follicles with different diameter sizes were increased, meanwhile, the diameter and growth speed of ovulatory follicle were significantly increased. Furthermore, the rates of estrous, ovulation, conception, and twinning rate were also significantly enhanced. These findings clearly illustrated that INH DNA vaccine was capable of promoting the follicle development, thereby improving the behavioral of estrous and ovulation, eventually leading to an augment in the conception rates and twinning rate of beef cattle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meng, Li, Xiao, Liu, Gao, Gong, Lan and Wang.)

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma., Competing Interests: Conflicts of Interest and Source of Funding: This work was supported by the Englander Institute for Precision Medicine and by the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine. The work at Memorial Sloan Kettering Cancer Center was funded in part by the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. M.F.L., J.S.M.M., and E.P. are employees at Isabl, Inc. G.G. is a consultant for Isabl. For the remaining authors none were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group., Methods: A total of 175 menopausal women were selected and divided into the osteoporosis group ( N = 90) and the control group ( N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), β-collagen special sequence (β-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression., Results: The level of BMD was decreased and the levels of OC, β-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value., Conclusion: AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, β-CTX, BALP, AMH, and InhB., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor., Objectives: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors., Method: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis., Results: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m 2 . Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism., Conclusion: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects., Competing Interests: The authors declare no competing interests., (Thieme. All rights reserved.)