Supplementary data for: Reproductive deficits induced by prenatal anti-Mullerian hormone exposure require androgen receptor in kisspeptin cells

Polycystic ovary syndrome (PCOS) is a common reproductive disorder
characterized by elevated androgens and anti-Mullerian hormone (AMH).
These hormones remain elevated throughout pregnancy, and potential effects
of hormone exposure on offspring from women with PCOS remain largely
unexplored. Expanding on recent reports of prenatal AMH exposure in mice,
we have fully characterized the reproductive consequences of prenatal AMH
(pAMH) exposure throughout the lifespan of first- and second-generation
offspring of both sexes. We also sought to elucidate mechanisms underlying
pAMH-induced reproductive effects. There is a known reciprocal
relationship between AMH and androgens, and in PCOS and PCOS-like animal
models, androgen feedback is dysregulated at the level the hypothalamus.
Kisspeptin neurons express androgen receptors and play a critical role in
sexual development and function. We therefore hypothesized that
pAMH-induced reproductive phenotypes would be mediated by androgen
signaling at the level of kisspeptin cells. We tested the pAMH model in
kisspeptin-specific androgen receptor knockout (KARKO) mice and found that
virtually all pAMH-induced phenotypes assayed are eliminated in KARKO
offspring compared to littermate controls. By demonstrating the necessity
of androgen receptor in kisspeptin cells to induce pAMH phenotypes, we
have advanced understanding of the interactions between AMH and androgens
in the context of prenatal exposure, which could have significant
implications for children of women with PCOS.