Experimental diabetes impairs rat embryo development during the preimplantation period

Abstract

Congenital malformations and early fetal losses are still the main complications of diabetic pregnancy. Whether the diabetic state affects the early embryo development during the preimplantation period is not known. To understand better the early steps of embryo growth, we collected the embryonic structures from the uterine horns of pregnant diabetic rats on day 5 of pregnancy. Diabetes was induced by streptozotocin (50 mg/kg) injection, 7, 14 or 21 days before mating. The morphological analysis revealed a lower rate of blastocysts (72% of all structures) and an increased rate of morulae (19.5%) in diabetic rats, compared to control animals (86.7 and 7.9% respectively). Hence, diabetic rats had fewer blastocysts (5.5 +/- 2.9 per rat) and more morulae (1.5 +/- 1.7) than control animals (7.2 +/- 2.7 and 0.66 +/- 1.2 respectively). Moreover, blastocysts from diabetic rats had fewer nuclei (26.9 +/- 7.3 per blastocyst) than blastocysts from control animals (31 +/- 6.1). In another set of experiments, subdiabetogenic doses of streptozotocin were administered. In rats injected with 25 mg/kg, neither the glycaemia, nor the morphological aspects of the embryos, nor the number of blastocyst nuclei differed from the control animals. In the animals receiving 35 mg/kg, the glycaemia was increased to approximately twice the control group value. However, the embryonic morphology and the nuclei counting of the blastocysts were similar to those of the fully diabetic group injected with 50 mg of streptozotocin. These results show that experimentally induced diabetes, even of a rather mild degree, affects the embryo development during the preimplantation period. The recovered embryos appear less mature and less developed.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro study of the carry-over effect associated with early diabetic embryopathy in the rat

“…On day 5 of pregnancy, diabetic rats were tested for their blood glucose concentration and those with a glycaemia above 11 mmol/1 were ether anaesthetized. Preimplantation embryos were collected from the uterine horns and immediately transferred onto an inverted phase-contrast microscope [7].…”

“…Interesting data pertaining to this issue have been obtained in experiments showing that preimplantation embryos from either drug-treated or spontaneous diabetic mice have a decreased ability to develop in vitro when maintained under the same culture conditions as control embryos [5,6]. These observations were made at the morphological level, however, and it is not known whether such a discrepancy in growth potential extends to more subtle differences in the rate of embryonic cell proliferation and differentiation.In a previous study on the impact of the maternal diabetic condition on preimplantation growth in vivo, we demonstrated that blastocysts collected from diabetic rats contained fewer cells than control embryos [7] and that cells from the lineage responsible for forming the fetus were more affected in their proliferation than the cell population that gives rise to the placenta [8]. This deficiency in preimplantation development was corrected by treating the dia-…”

“…In a previous study on the impact of the maternal diabetic condition on preimplantation growth in vivo, we demonstrated that blastocysts collected from diabetic rats contained fewer cells than control embryos [7] and that cells from the lineage responsible for forming the fetus were more affected in their proliferation than the cell population that gives rise to the placenta [8]. This deficiency in preimplantation development was corrected by treating the dia-betic pregnant rats with insulin shortly after conception [9].…”

Modulations physiologiques et immunologiques du diabète gestationnel et de la macrosomie : implication de la programmation in utero

“…Dans le but de comprendre le rôle du métabolisme lipidique dans l'étiopathologie de la macrosomie, nous avons développé dans notre laboratoire un modèle animal. Il a été démontré que l'administration de streptozotocine (STZ), avant la grossesse, affecte la fertilité et altère le développement de l'embryon pendant la période de pré-implantation (Vercheval et al, 1990). Pour cette raison, dans notre modèle, nous avons injecté, à des rattes Wistar femelles, par voie intrapéritonéale, une dose unique de 40 mg/kg de poids corporel de STZ, au 5 e jour de la gestation et n'avons observé aucun effet délétère sur le développement de l'embryon.…”

The Effects of Maternal Periconceptional Ethanol Exposure on the Development of the Pre-Implantation Embryo, Placenta, and the Influence of the Uterine Environment

“…Altered oocyte maturation, ↓ blastocysts, total, TE and ICM number ↑ Morulae ↓ Outgrowth of P-TGC at 72h culture (Diamond et al, 1989, Lea et al, 1996, Moley et al, 1991, Pampfer et al, 1994, Vercheval et al, 1990) High Fat Diet, mouse, in vivo, -16 weeks -E0 or E4, in vitro to E5 ↓ Oocyte quality, ICM and blastocyst number, ↑ TE cells ↑ Igf2R expression (Jungheim et al, 2010, Minge et al, 2008 Ethanol, mouse, in vitro, oocytes, 1-, 2-or 4-cell embryos exposed to 0-2% (w/v) EtOH on one day, cultured to blastocyst stage.…”