Dataset Information

A Hormone That Lost Its Receptor: Anti-Mullerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination.

ABSTRACT: Fetal mammalian testes secrete Anti-Müllerian hormone (Amh), which inhibits female reproductive tract (Müllerian duct) development. Amh also derives from mature mammalian ovarian follicles, which marks oocyte reserve and characterizes polycystic ovarian syndrome. Zebrafish (Danio rerio) lacks Müllerian ducts and the Amh receptor gene amhr2 but, curiously, retains amh To discover the roles of Amh in the absence of Müllerian ducts and the ancestral receptor gene, we made amh null alleles in zebrafish. Results showed that normal amh prevents female-biased sex ratios. Adult male amh mutants had enormous testes, half of which contained immature oocytes, demonstrating that Amh regulates male germ cell accumulation and inhibits oocyte development or survival. Mutant males formed sperm ducts and some produced a few offspring. Young female mutants laid a few fertile eggs, so they also had functional sex ducts. Older amh mutants accumulated nonvitellogenic follicles in exceedingly large but sterile ovaries, showing that Amh helps control ovarian follicle maturation and proliferation. RNA-sequencing data partitioned juveniles at 21 days postfertilization (dpf) into two groups that each contained mutant and wild-type fish. Group21-1 upregulated ovary genes compared to Group21-2, which were likely developing as males. By 35 dpf, transcriptomes distinguished males from females and, within each sex, mutants from wild types. In adult mutants, ovaries greatly underexpressed granulosa and theca genes, and testes underexpressed Leydig cell genes. These results show that ancestral Amh functions included development of the gonadal soma in ovaries and testes and regulation of gamete proliferation and maturation. A major gap in our understanding is the identity of the gene encoding a zebrafish Amh receptor; we show here that the loss of amhr2 is associated with the breakpoint of a chromosome rearrangement shared among cyprinid fishes.

SUBMITTER: Yan YL

PROVIDER: S-EPMC6781894 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

A Hormone That Lost Its Receptor: Anti-Müllerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination.

Yan Yi-Lin YL Batzel Peter P Titus Tom T Sydes Jason J Desvignes Thomas T BreMiller Ruth R Draper Bruce B Postlethwait John H JH

Genetics 20190809 2

Fetal mammalian testes secrete Anti-Müllerian hormone (Amh), which inhibits female reproductive tract (Müllerian duct) development. Amh also derives from mature mammalian ovarian follicles, which marks oocyte reserve and characterizes polycystic ovarian syndrome. Zebrafish (Danio rerio) lacks Müllerian ducts and the Amh receptor gene amhr2 but, curiously, retains amh To discover the roles of Amh in the absence of Müllerian ducts and the ancestral receptor gene, we made am ...[more]

PMID: 31399485

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Project description:Introduction: Polycystic ovarian syndrome (PCOS) is a leading cause of female subfertility worldwide, however due to the heterogeneity of the disorder, the criteria for diagnosis remains subject to conjecture. In the present study, we evaluate the utility of serum Anti-Müllerian hormone (AMH) in the diagnosis of menstrual disturbance due to PCOS. Method: Menstrual cycle length, serum AMH, gonadotropin and sex-hormone levels, total antral follicle count (AFC), body mass index (BMI) and ovarian morphology on ultrasound were analyzed in a cohort of 187 non-obese women, aged 18-35 years, screened for participation in a clinical trial of fertility treatment between 2013 and 2016 at a tertiary reproductive endocrine center. Results: Serum AMH was higher in women with menstrual disturbance when compared to those with regular cycles (65.6 vs. 34.8 pmol/L; P < 0.0001). The odds of menstrual disturbance was increased 28.5-fold (95% CI 3.6-227.3) in women with serum AMH >60 pmol/L, in comparison to those with an AMH < 15 pmol/L. AMH better discriminated women with menstrual disturbance (area under ROC 0.77) from those with regular menstrual cycles than AFC (area under ROC 0.67), however the combination of the two markers increased discrimination than either measure alone (0.83; 95% CI 0.77-0.89). Serum AMH was higher in women with all three cardinal features of PCOS (menstrual disturbance, hyperandrogenism, polycystic ovarian morphology) when compared to women with none of these features (65.6 vs. 14.6 pmol/L; P < 0.0001). The odds of menstrual disturbance were increased by 10.7-fold (95% CI 2.4-47.1) in women with bilateral polycystic morphology ovaries than those with normal ovarian morphology. BMI was a stronger predictor of free androgen index (FAI) than either AMH or AFC. Conclusion: Serum AMH could serve as a useful biomarker to indicate the risk of menstrual disturbance due to PCOS. Women with higher AMH levels had increased rates of menstrual disturbance and an increased number of features of PCOS.

Dataset Information

A Hormone That Lost Its Receptor: Anti-Mullerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination.

Publications

A Hormone That Lost Its Receptor: Anti-Müllerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination.

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