Effects of Alloxan-induced Diabetes on Corpus Luteum Function in the Pseudopregnant Rat

Abstract

The effects of alloxan-induced diabetes mellitus on rat ovarian structure and function were examined throughout pseudopregnancy (PSP). Animals received either saline (C) or alloxan (40 mg/kg) treatment on the day of proestrus (PA) preceding PSP or on day 1 (D-1A) of PSP (day 0 = ovulation). Serum samples were analyzed by radioimmunoassay for progesterone (P) and 17-beta-estradiol (E) levels and compared with the corresponding changes in ovarian and uterine weights in C, PA, and D-1A rats. In addition, the effects of daily treatment with 6 IU ovine insulin (AI) on serum P levels were assessed in D-1A-treated rats and compared with controls. Alloxan treatment effectively elevated blood glucose levels (P less than or equal to 0.01) in PA and D-1A groups as compared with controls or AI rats. Alloxan treatment reduced both ovarian and uterine weights of PA and D-1A groups as compared with C and AI rats. Serum P levels were significantly reduced in PA (P less than or equal to 0.01) and D-1A (P less than or equal to 0.05-0.01) rats as compared with control rats throughout PSP. Daily insulin treatment reversed the suppressive effects of D-1A treatment on serum P levels, but did not restore luteal function to control levels. Neither C nor D-1A groups exhibited any marked differences in serum E levels throughout PSP. The results of these studies indicate that the administration of alloxan before the onset of PSP effectively inhibits luteal function, whereas D-1A treatment induces early luteolysis as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes-Induced, Progressive Endometrial Involution Characterization of Periluminal Epithelial Lipoatrophy

“…The results of the present studies extend previous reports of reproductive tract atrophy, utero-ovarian cellular degeneration, and depressed ovarian steroidogenesis resulting from the chronic diabetes syndrome in various genetic and experimentally induced hyperglycemic models (1,2,5,8,13,15,21) by identifying the progressive nature of the hypercytolipidemia that characterizes this metabolic mutation. The evaluation of the progressive imbibition and accumulation of cytoplasmic lipid stores observed in the current studies correlates with the temporal expression of the hyperglycemic-hyperinsulinemic state and the enhanced tissue triglyceride levels present in endometrial samples of db/db groups relative to controls.…”

“…The recognized lipolytic actions of administered estrogenic steroids (5) or etiocholanolones (22) may effectively maintain endometrial cellular integrity by reversing or suppressing the deleterious actions of chronic lipid inbibition on reproductive tract structure by normalizing intracellular homeostatic conditions and systemic counterregulatory, noradrenergic influences (13). The observed baso-polar epithelial lipid accumulation that took place via enhanced basal membrane transport from stromal periluminal vasculature may have occurred as a result of the diabetes-associated compromise of endometrial blood flow perfusion rates (2,8,23). Uteroovarian blood flow is diminished in diabetic subjects, inducing endometrial capillary vascular expansion with diminished flow exchange rates (2).…”

“…Research has indicated that the acute (initial) expression of the mutation-induced cellular alterations continue to expand through chronic expression periods, culminating in tissue and organ involution, depressed metabolic activity (1,3,8,9), inhibition of adrenergic counterregulatory influences (11)(12)(13)(14)(15)(16), and, ultimately, reproductive tract atrophy. The severity of these cellular changes mimic the enhanced blood glucose and triglyceride concentrations that continue to increase across successive time periods (7,17,18).…”

“…Characterized by ovarian follicular atresia (4), inhibition of follicular recruitment (4), depressed ovarian steroid hormone production (1,3,5), refractory responsiveness to gonadotropin stimulation (6), and failure of corpus luteum formation (4,7,8), the maturation of the reproductive tract is developmentally and structurally impaired as compared with littermate controls (ϩ/?). Uterine structural parameters influenced by the expression of the db/db mutation include a marked depression in uterine epithelial cellular integrity (1,7), depressed responsivity to ovarian steroid hormone therapy (7,9,10), suppressed mitotic indexes (3), and premature tissue involution (2), accompanied by an enhanced cytoplasmic lipid inclusion volume (4).…”

Estabelecimento de um modelo de gestação complicada por diabetes tipo 1 em camundongos: avaliação do seu impacto sobre o ambiente uterino no início da gestação.

“…Potencialmente todos os componentes que formam o eixo do sistema reprodutor feminino podem ser afetados pelo diabetes, incluindo as estruturas neuroendócrinas que controlam o ciclo reprodutivo, o hipotálamo e a hipófise (Kirchick et al, 1979;Garris et al, 1982), até os ovários (Chieri et al, 1969;Garris et al, 1984) e o útero (Frederick et al, 1985), comprometendo o ciclo reprodutivo e a gestação.…”