Fetal resorption coincides with dysregulated LH secretion in AMH-overexpressing mice

in Journal of Endocrinology
Authors:
Yiran Zhou Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Christine Neyt Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Nicola J Batchelor Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Rebecca L Kelley School of Biosciences, University of Melbourne, Melbourne, Australia

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Karmilla Jaafar Amsak Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Greg M Anderson Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand

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Dorothy E Oorschot Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
Brain Health Research Centre, University of Otago, Dunedin, New Zealand

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Christine L Jasoni Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand

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Jane E Girling Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Michael W Pankhurst Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

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Correspondence should be addressed to M W Pankhurst: michael.pankhurst@otago.ac.nz
DOI:
https://doi.org/10.1530/JOE-21-0430
Volume/Issue:
Volume 253: Issue 2
Article Type:
Research Article
Page Range:
53–62
Online Publication Date:
05 Mar 2022
Copyright:
© Society for Endocrinology 2022
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Female anti-Müllerian hormone (AMH) overexpressing (Thy1.2-AMHTg/0) mice experience fetal resorption (miscarriage) by mid-gestation. This study examined whether the ovary, uterine implantation sites and hypothalamus are potential sites of AMH action, as AMH type-2 receptor (AMHR2) expression is reported in each tissue. Pregnancy in Thy1.2-AMHTg/0 mice was compared to wild-type (WT) mice via histological examination of implantation sites, hormone assays, embryo culture and embryo transfer. Uterine AMH and AMHR2 expression was examined by RT-qPCR and immunohistochemistry. The first signs of fetal resorption in the Thy1.2-AMHTg/0 dams occurred at embryonic day 9.5 (E9.5) with 100% of fetuses resorbing by E13.5. Cultured embryos from Thy1.2-AMHTg/0 dams had largely normal developmental rates but a small proportion experienced a minor developmental delay relative to embryos from WT dams. However, embryos transferred from WT donor females always failed to survive to term when transferred into Thy1.2-AMHTg/0 dams. Amh and Amhr2 mRNA was detected in the gravid uterus but at very low levels relative to expression in the ovaries. Progesterone and estradiol levels were not significantly different between WT and Thy1.2-AMHTg/0 dams during pregnancy but luteinizing hormone (LH) levels were significantly elevated in Thy1.2-AMHTg/0 dams at E9.5 and E13.5 relative to WT dams. Collectively, these experiments suggest that AMH overexpression does not cause fetal resorption through an effect on oocytes or preimplantation embryo development. The Thy1.2-AMHTg/0 fetal resorption phenotype is nearly identical to that of transgenic LH overexpression models, suggesting that neuroendocrine mechanisms may be involved in the cause of the miscarriage.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2022
Page(s):
10
Article Type:
Research Article
Received Date:
21 Jan 2022
Accepted Date:
28 Jan 2022
Print Publication Date:
01 May 2022
Online Publication Date:
05 Mar 2022
Keywords:
antimullerian hormone; miscarriage; pregnancy; uterus

  • Abercrombie M 1946 Estimation of nuclear population from microtome sections. Anatomical Record 94 239–247. (https://doi.org/10.1002/ar.1090940210)

  • Baarends WM, Uilenbroek JT, Kramer P, Hoogerbrugge JW, van Leeuwen EC, Themmen AP & Grootegoed JA 1995 Anti-Mullerian hormone and anti-Mullerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology 136 4951–4962. (https://doi.org/10.1210/endo.136.11.7588229)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Behringer RR, Cate RL, Froelick GJ, Palmiter RD & Brinster RL 1990 Abnormal sexual development in transgenic mice chronically expressing Mullerian inhibiting substance. Nature 345 167–170. (https://doi.org/10.1038/345167a0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cameron SH, Alwakeel AJ, Goddard L, Hobbs CE, Gowing EK, Barnett ER, Kohe SE, Sizemore RJ & Oorschot DE 2015 Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia. Molecular and Cellular Neurosciences 68 56–72. (https://doi.org/10.1016/j.mcn.2015.03.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cimino I, Casoni F, Liu X, Messina A, Parkash J, Jamin SP, Catteau-Jonard S, Collier F, Baroncini M & Dewailly D et al.2016 Novel role for anti-Mullerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nature Communications 7 10055. (https://doi.org/10.1038/ncomms10055)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Clarke TR, Hoshiya Y, Yi SE, Liu X, Lyons KM & Donahoe PK 2001 Mullerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression. Molecular Endocrinology 15 946–959. (https://doi.org/10.1210/mend.15.6.0664)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Deb K, Reese J & Paria BC 2006 Methodologies to study implantation in mice. Methods in Molecular Medicine 121 9–34. (https://doi.org/10.1385/1-59259-983-4:007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA & Themmen AP 1999 Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140 5789–5796. (https://doi.org/10.1210/endo.140.12.7204)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR, Matzuk MM, Rose UM, de Jong FH, Uilenbroek JT & Grootegoed JA et al.2001 Anti-Mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 142 4891–4899. (https://doi.org/10.1210/endo.142.11.8486)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Garrel G, Racine C, L’Hote D, Denoyelle C, Guigon CJ, di Clemente N & Cohen-Tannoudji J 2016 Anti-Mullerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty. Scientific Reports 6 23790. (https://doi.org/10.1038/srep23790)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Garrel G, Denoyelle C, L’Hote D, Picard JY, Teixeira J, Kaiser UB, Laverriere JN & Cohen-Tannoudji J 2019 GnRH transactivates human AMH receptor gene via Egr1 and FOXO1 in gonadotrope cells. Neuroendocrinology 108 65–83. (https://doi.org/10.1159/000494890)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Grattan DR, Steyn FJ, Kokay IC, Anderson GM & Bunn SJ 2008 Pregnancy-induced adaptation in the neuroendocrine control of prolactin secretion. Journal of Neuroendocrinology 20 497–507. (https://doi.org/10.1111/j.1365-2826.2008.01661.x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hayes E, Kushnir V, Ma X, Biswas A, Prizant H, Gleicher N & Sen A 2016 Intra-cellular mechanism of anti-Mullerian hormone (AMH) in regulation of follicular development. Molecular and Cellular Endocrinology 433 56–65. (https://doi.org/10.1016/j.mce.2016.05.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kano M, Sosulski AE, Zhang L, Saatcioglu HD, Wang D, Nagykery N, Sabatini ME, Gao G, Donahoe PK & Pepin D 2017 AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy. PNAS 114 E1688–E1697. (https://doi.org/10.1073/pnas.1620729114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kereilwe O, Pandey K, Borromeo V & Kadokawa H 2018 Anti-Mullerian hormone receptor type 2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion. Reproduction, Fertility, and Development 30 1192–1203. (https://doi.org/10.1071/RD17377)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lane M & Gardner DK 2001 Vitrification of mouse oocytes using a nylon loop. Molecular Reproduction and Development 58 342–347. (https://doi.org/10.1002/1098-2795(200103)58:3<342::AID-MRD13>3.0.CO;2-X)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Malone SA, Papadakis GE, Messina A, Mimouni NEH, Trova S, Imbernon M, Allet C, Cimino I, Acierno J & Cassatella D et al.2019 Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism. eLife 8 e47198. (https://doi.org/10.7554/eLife.47198)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mann RJ, Keri RA & Nilson JH 1999 Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure. Endocrinology 140 2592–2601. (https://doi.org/10.1210/endo.140.6.6927)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McLennan IS, Koishi K, Batchelor NJ & Pankhurst MW 2018 Mice with either diminished or elevated levels of anti-Müllerian hormone (AMH) have decreased litter sizes. Biology of Reproduction 98 54–62. (https://doi.org/10.1093/biolre/iox151)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Novembri R, Funghi L, Voltolini C, Belmonte G, Vannuccini S, Torricelli M & Petraglia F 2015 Placenta expresses anti-Mullerian hormone and its receptor: sex-related difference in fetal membranes. Placenta 36 731–737. (https://doi.org/10.1016/j.placenta.2015.04.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Orvis GD, Jamin SP, Kwan KM, Mishina Y, Kaartinen VM, Huang S, Roberts AB, Umans L, Huylebroeck D & Zwijsen A et al.2008 Functional redundancy of TGF-beta family type I receptors and receptor-Smads in mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse. Biology of Reproduction 78 994–1001. (https://doi.org/10.1095/biolreprod.107.066605)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pankhurst MW, Kelley RL, Sanders RL, Woodcock SR, Oorschot DE & Batchelor NJ 2018 Anti-Mullerian hormone overexpression restricts preantral ovarian follicle survival. Journal of Endocrinology 237 153–163. (https://doi.org/10.1530/JOE-18-0005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Percie du Sert N, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U & Emerson M et al.2020 Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biology 18 e3000411. (https://doi.org/10.1371/journal.pbio.3000411)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Renaud EJ, MacLaughlin DT, Oliva E, Rueda BR & Donahoe PK 2005 Endometrial cancer is a receptor-mediated target for Mullerian inhibiting substance. PNAS 102 111–116. (https://doi.org/10.1073/pnas.0407772101)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Saatcioglu HD, Kano M, Horn H, Zhang L, Samore W, Nagykery N, Meinsohn MC, Hyun M, Suliman R & Poulo J et al.2019 Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility. eLife 8 e46349. (https://doi.org/10.7554/eLife.46349)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Steyn FJ, Wan Y, Clarkson J, Veldhuis JD, Herbison AE & Chen C 2013 Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice. Endocrinology 154 4939–4945. (https://doi.org/10.1210/en.2013-1502)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tata B, Mimouni NEH, Barbotin AL, Malone SA, Loyens A, Pigny P, Dewailly D, Catteau-Jonard S, Sundstrom-Poromaa I & Piltonen TT et al.2018 Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine 24 834–846. (https://doi.org/10.1038/s41591-018-0035-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang J, Dicken C, Lustbader JW & Tortoriello DV 2009 Evidence for a Mullerian-inhibiting substance autocrine/paracrine system in adult human endometrium. Fertility and Sterility 91 1195–1203. (https://doi.org/10.1016/j.fertnstert.2008.01.028)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC & Themmen AP 2004 Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Molecular Human Reproduction 10 77–83. (https://doi.org/10.1093/molehr/gah015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Y, Hu M, Yang F, Zhang Y, Ma S, Zhang D, Wang X, Sferruzzi-Perri AN, Wu X & Brannstrom M et al.2021 Increased uterine androgen receptor protein abundance results in implantation and mitochondrial defects in pregnant rats with hyperandrogenism and insulin resistance. Journal of Molecular Medicine 99 1427–1446. (https://doi.org/10.1007/s00109-021-02104-z)

    • PubMed
    • Search Google Scholar
    • Export Citation