Loss of Anti-Müllerian Hormone Signaling in Mice Affects Trabecular Bone Mass in a Sex- and Age-Dependent Manner

Christiane van As, Marijke Koedam, Anke McLuskey, Piet Kramer, Najiba Lahlou, Bram C. J. van der Eerden, Jenny A. Visser
Endocrinology · 2022 · vol. 163(11) · doi:10.1210/endocr/bqac157 · PMID:36155779 · PMC9576916 · W4297256566
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AMH signaling deficiency causes sex- and age-dependent trabecular bone loss in mice, with reproductive-aged females exhibiting higher bone volume due to altered ovarian follicle dynamics.

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Abstract

Ovariectomy-induced osteoporosis in mice results from an abrupt loss of ovarian sex steroids. Anti-Müllerian hormone knockout (AMHKO) mice show a gradual but accelerated ovarian aging, and therefore may better resemble osteoporosis following natural menopause. To study the impact of AMH signaling deficiency on bone, we compared trabecular and cortical bone parameters in 2-, 4-, 10-, and 16-month-old male and female wild-type (WT), AMHKO, and AMH type II receptor knockout (MRKI) mice using micro computed tomography (microCT). Goldner's staining was performed to confirm the observed bone phenotype. Both male and female AMHKO and MRKI mice showed age-dependent loss of trabecular bone (P < 0.001). However, reproductive-aged female AMHKO and MRKI mice had higher BV/TV compared with WT (P < 0.001), coinciding with increased growing follicle numbers (P < 0.05) and increased estrus inhibin B levels (AMHKO: P < 0.001; MRKI: P < 0.05) but normal inhibin A, estrogen, and progesterone levels. In aged female AMHKO and MRKI mice BV/TV did not differ from WT mice due to greater trabecular bone loss between 10 and 16 months compared with WT mice. At these ages, AMHKO and MRKI mice had reduced growing follicle numbers (P < 0.05) and reduced inhibin B levels (P < 0.001). At age 10 months, female MRKI mice had increased cortical bone parameters compared with WT mice (P < 0.01). Bone parameters of male AMHKO and MRKI mice did not differ from male WT mice. In conclusion, AMH signaling deficiency results in a sex- and age-dependent effect on predominantly trabecular bone. Our results further suggest that reproductive hormones beyond estrogen may contribute to bone homeostasis.

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MeSH descriptors

Anti-Mullerian Hormone Anti-Mullerian Hormone Osteoporosis Osteoporosis Animals Cancellous Bone Cancellous Bone Estrogens Female Male Mice Mice, Knockout Progesterone X-Ray Microtomography

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