Abstract
Female anti-Müllerian hormone (AMH) overexpressing (
Thy1.2-AMH
Tg/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-AMH
Tg/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-AMH
Tg/0
dams occurred at embryonic day 9.5 (E9.5) with 100% of fetuses resorbing by E13.5. Cultured embryos from
Thy1.2-AMH
Tg/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-AMH
Tg/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-AMH
Tg/0
dams during pregnancy but luteinizing hormone (LH) levels were significantly elevated in
Thy1.2-AMH
Tg/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-AMH
Tg/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.