Hypercytolipidemia promotes diabetes (db/db) mutation-associated utero-ovarian involution: counter-regulatory influences of progesterone  David R Garris, Bryan L Garris  Pathophysiology  Volume 11, Issue 1, Pages 41-50 (July 2004) DOI: 10.1016/j.pathophys.2004.02.001

Fig. 1 Body weights (g) of control (+/?) and diabetic (db/db) C57BL/KsJ mice between 4 and 16 weeks of age are demonstrated as group means (N=5–8 per group) and the influences of either oil-vehicle (0.1ml/3.5 days sc) or P-HRx injections (2.0mg/3.5 days sc) denoted. No significant differences existed between either (+/?) treatment group, receiving either oil or P injections, throughout the experimental period. All (db/db) mice, treated with oil or P-HRx, demonstrated body weights which were significantly (P≤0.05) greater than comparable (+/?) treatment groups (∗). In addition, between weeks 8 and 16, all (db/db)-P-HRx mice demonstrated a significant decline in body weights relative to oil-HRx-(db/db) mice (#). Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 2 Uterine and ovarian tissue weights at 16 weeks of age are depicted for control (+/?) and diabetic (db/db) C57BL/KsJ mice following either oil- or P-HRx between 4 and 16 weeks of age. Both uterine and ovarian weights of (db/db)-oil-treated group were significantly (∗P≤0.05) lower than those of comparable (+/?) controls. The P-HRx induced a significant increase in uterine weights in (db/db) mice relative to oil-HRx (#) and restored (db/db) tissue weights to that of oil-HRx (+/?) groups. P-HRx did not stimulate (db/db) ovarian weight increases relative to those demonstrated by (+/?)-P-HRx groups. (∗) Significant intergroup differences (P<0.05) relative to genotype. (#) Significant intra-group differences relative to treatment regime. Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 3 Blood glucose (mg/dl) and serum insulin (pg/ml) concentrations are represented as group means from control (C) and (db/db) groups (N: 5–8 per group) at 16 weeks of age following either oil- or P-HRx treatments. (∗) Significant intergroup differences between (+/?) and (db/db) mice treated with either oil vehicle or P-HRx injections. The influence of P-HRx on intra-group differences for these parameters is denoted as (#). Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 4 Photomicrographs (1000×) of the uterine epithelial endometrial tissue layer, demonstrated by high-resolution light (A and B) or digital chemospectrophotometry for cytoplasmic lipid depositions (C–F), collected from 16-week-old control (+/?: A, C, E) and diabetic (db/db: B, D, F) mice following either oil (A–D) or P-HRx (E and F) treatments. The lipid deposition (arrows) noted in the basal pole of (+/?) uterine epithelial cells (A) was markedly enhanced by the DOS expressed in (db/db) mice (B). Examination by DCSP depicts the intra-cytoplasmic lipid pools as fluorescent yellow deposits at normal concentrations in controls (+/?: C) and elevated densities in diabetics (db/db: D), including apical cytoplasmic lipid depositions. Following P-HRx, the DCSP localization of lipid accumulations in both the (+/?: E) and (db/db: F) groups had been moderated to that observed in oil-HRx controls (C), indicating the cytolipid-suppressing effectiveness of the P-HRx therapy in diabetic groups. Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 5 Photomicrographs (1000×) of secondary, non-atretic ovarian follicles of control (+/?: A, C, E) and diabetic (db/db: B, D, F) 16-week-old C57BL/KsJ mice following either oil (A–D) or P-HRx (E and F) injections. High-resolution light micrographs (A and B) revealed the high density of interstitial (I), thecal (T) layer and follicular granulosa (G) cell lipid depositions observed in oil-HRx (db/db) groups (B) relative to controls (A). By DCSP, the normal distribution pattern and density of I and T lipid deposits were enhanced in both (+/?: C) and (db/db: D) groups. The effectiveness of P-HRx on reducing the G and T lipid deposit densities in diabetic (F) mice, to comparable P-HRx-treated (+/?: E) controls, was denoted by the remarkable reduction in total lipid accumulation as indicated by the reduced intensity of fluorescent yellow lipid pools compared to oil-HRx (db/db: D) mice. P-HRx did not disperse lipodepositions localized in I tissue compartments in (db/db) groups (F) to intensities noted in corresponding (+/?) mice (E). Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 6 Influences of P-HRx on uterine and ovarian tissue lipase activities are represented as group (N=3–6) mean values (±S.E.M.) for control (+/?) and diabetic (db/db) C57BL/KsJ mice at 16 weeks of age. (∗) Genotype-related significant (P≤0.05) differences between (+/?) and (db/db) groups relative to treatment regime. Intra-group, treatment-related differences are denoted by (#). N.D.: non-detectable. Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)

Fig. 7 The influences of both the diabetes (db/db) mutation and P-HRx treatments on utero-ovarian insulin binding, insulin membrane receptor populations, and tissue glucose uptake rates are presented as group (N=5–8 groups) mean values (±S.E.M.) for 16-week-old C57BL/KsJ mice. (∗) Significant (P≤0.05) intergroup differences for each parameter for both oil- and P-HRx-treated groups. Pathophysiology 2004 11, 41-50DOI: (10.1016/j.pathophys.2004.02.001)