Effects of long‐term diabetes on the structure and cell proliferation of the myometrium in the early pregnancy of mice

Abstract

It is known that the development of diabetic complications in human pregnancy is directly related to the severity and the duration of this pathology. In this study, we developed a model of long-term type 1 diabetes to investigate its effects on the cytoarchitecture, extracellular matrix and cell proliferation during the first adaptation phase of the myometrium for pregnancy. A single dose of alloxan was used to induce diabetes in mice prior to pregnancy. To identify the temporal effects of diabetes the mice were divided into two groups: Group D1 (females that became pregnant 90-100 days after alloxan); Group D2 (females that became pregnant 100-110 days after alloxan). Uterine samples were collected after 168 h of pregnancy and processed for light and electron microscopy. In both groups the histomorphometric evaluation showed that diabetes promoted narrowing of the myometrial muscle layers which was correlated with decreased cell proliferation demonstrated by PCNA immunodetection. In D1, diabetes increased the distance between muscle layers and promoted oedema. Contrarily, in D2 the distance between muscle layers decreased and, instead of oedema, there was a markedly deposition of collagen in the myometrium. Ultrastructural analysis showed that diabetes affects the organization of the smooth muscle cells and their myofilaments. Consistently, the immunoreaction for smooth muscle α-actin revealed clear disorganization of the contractile apparatus in both diabetic groups. In conclusion, the present model demonstrated that long-term diabetes promotes significant alterations in the myometrium in a time-sensitive manner. Together, these alterations indicate that diabetes impairs the first phenotypic adaptation phase of the pregnant myometrium.

Placental development during early pregnancy in sheep: Effects of embryo origin on fetal and placental growth and global methylation

“…Moreover, in pregnancies compromised by diabetes, both increased and decreased placental cell proliferation was observed in rats [58,59]. For diabetic mice, decreased cell proliferation was reported in the myometrium during early pregnancy [60]. Conversely, cell proliferation was similar in human term placental from diabetic and non-diabetic mothers [61].…”

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.

“…The present and a previous study by our group 33 , highlighted the severity, duration and the presence of vasculopathy as major risk factors responsible for adverse outcome in diabetic pregnancies. However, the contribution of these factors to the development of pregnancy complications has not been adequately explored in animal models.…”

“…According to its duration, diabetes promoted edema between muscle layers, indicating the development of vasculopathy, which was followed by fibrosis and atrophy of the myometrium 33 . Overall, these results pointed out the importance of the temporal factor (i.e.…”

“…Estes resultados mostram que o diabetes afeta a primeira fase de adaptação do miométrio durante a gestação, e que estas alterações só se desenvolvem após um período longo de submissão ao diabetes (Favaro et al, 2010 Considerando os efeitos inibitórios do decorim sobre a proliferação celular (Yamaguchi, Ruoslahti, 1988), nós hipotetizamos que a diminuição desta molécula nas camadas musculares pode atuar na conservação da proliferação celular prejudicada pelo diabetes. Foi sugerido que durante o ciclo estral, a inibição do decorim na camada superficial do endométrio tem o papel de promover a proliferação celular neste compartimento .…”

Effect of Orally Administered Camel Milk in Alloxan® Induced Albino Rats: Long Term Study on Maternal Uterus and Neonates Selected Organs

“…Uterine decidualization phenomenon has been worsening by DM which contributes in the production of pro-inflammatory uterine RESEARCH ARTICLE condition through generating free radicals leading to embryopathies. Histologically, DM promotes the thinning of uterine myometrium and endometrium (Favaro et al, 2010(Favaro et al, , 2013Usman et al, 2018). Declined smooth muscles with vanished oxytocin contractive myometrium response was also reported in DM.…”