Obesity is closely associated with reproductive disorders, including polycystic ovary syndrome (PCOS) and infertility. Diet-induced obesity in female mice has been suggested to accelerate primordial follicle  recruitment leading to premature ovarian aging. Early depletion of primordial follicle pool is also observed in mice lacking anti-Müllerian hormone (AMH) signalling, such as AMH deficient (AMHKO) mice and AMH type 2 receptor deficient (MRKI) mice. On the other hand, diet-induced obesity also results in disrupted estrous cyclicity and ovulatory failure, a phenotype resembling PCOS. To address this opposing aspects of infertility, ovarian aging and PCOS, female AMHKO and MRKI mice were exposed to a high fat high cholesterol diet (HFHCD).

Female AMH signalling deficient mice and their corresponding wild-type (WT) littermates at 30 days of age were fed a HFHCD or control diet (CD) for 14 weeks. Metabolic and reproductive parameters were assessed at the end of the treatment period.

HFHCD led to significantly increased body weight and total fat mass in WT, AMHKO and MRKI mice (P<0.01). HFHCD induced glucose intolerance, as assessed by IPGTT (P<0.01). However, AMH signaling deficient mice did not differ from WT mice. HFHCD-fed mice had a ~15% lower respiratory exchange ratio compared to CD-fed mice (P<0.01). Energy expenditure (EE) was significantly increased in HFHCD-fed WT mice compared to CD-fed WT mice. Interestingly, CD-fed AMHKO mice tended to have a higher EE compared to CD-fed WT mice (P=0.06) – which was not further increased upon HFHCD. HFHCD did not affect physical activity in all groups. Estrous cyclicity was irregular in HFHCD-fed mice compared to CD-fed mice, with HFHCD-fed mice showing a ~65% reduction in number of complete estrous cycle （P<0.01). No genotype difference was observed. Analysis of ovarian folliculogenesis and assessment of endocrine parameters is ongoing.

In summary, diet-induced obesity negatively affects metabolic and reproductive function, with mild effects of AMH signalling deficiency on studied metabolic phenotypes.