Fig. 1: An optimal dietary macronutrient balance rescues ovulatory dysfunction in a PCOS mouse model.

a Number of corpora lutea (CL) in control and PCOS mice, showing that regardless of diet PCOS mice exhibit fewer CL (P < 0.001). Significance determined by Mann–Whitney test, asterisk (*) indicates P-value <0.05. b–d Representative histological control (b) and PCOS (c) ovarian cross-sections, showing presence of CL in ovaries from PCOS mice with a macronutrient intake of C 20–30 kJ/day and F 15-25 kJ/day (d). White stars, corpora lutea. Magnification ×4, scale bar 500 µm. e–j 3D GAM response surfaces showing the relationship between macronutrient intake (kJ/day) and number of CL in control (e–g) and PCOS ovaries (h–j) showing restoration of ovulations in PCOS mice on a macronutrient intake of C 20–30 kJ/day and F 15–25 kJ/day (j). Red areas indicate the greatest value, which then decreases to the lowest value as the color shifts to blue. Regions with highest CL number for control (g) and PCOS (j) mice are encircled in red. k–m 3D GAM response surfaces showing the impact of main drivers (carbohydrate and fat) on CL numbers in control mice (k), PCOS mice (l) and the response difference (m), demonstrating a comparable ovulatory response between control and PCOS above a C intake of >20 kJ/day and F > 25 kJ/day. a, e–m n = 36 control and 35 PCOS mice. n % of time spent at each stage of the estrous cycle for control and PCOS mice, showing that a subset of PCOS mice did cycle through all estrous cycle stages. Significance determined by Mann–Whitney test, asterisk (*) indicates P-value <0.05, all P < 0.001. o–q Representative graphs of estrous-cycle patterns, showing restoration of cyclicity in a PCOS mouse with a dietary intake of 20 kJ/day C and 21 kJ/day F (q). r Response difference between control and PCOS mice for number of estrous cycles completed, demonstrating comparable estrous cycle response between control and PCOS mice at similar intakes that restore ovulatory response. n, r n = 93 control and 94 PCOS mice. a, n Data presented as violin plots, doted lines indicate the median and dashed lines the 25 and 75% percentiles.