High doses of estrogens cause embryonic mortality, and fetal and placental growth retardation in rats. This study addresses the physiological relevance of such findings. Estradiol benzoate (EB), by s.c. injection, or estradiol-17beta (E2), delivered by a miniosmotic pump, raised maternal E2 concentrations from only slightly above control values to 5-fold. EB (1 microgram/day) over Days 6-13, 8-13, and 11-13, and continuous infusion of E2 (15 ng/h; Days 10-13) reduced fetal survival to 0%, 0%, 22%, and 75%, respectively. Single injections of EB showed that its lethal effect declined rapidly over Days 9 (44% survival) to 13 (90% survival). Embryos died within 48 h, but death was not due to luteal failure since progesterone levels were maintained and progesterone administered with EB did not reduce mortality. Administration of EB at 1 microgram/day (Days 14-21) or E2 at 40 ng/h (Days 13-16) retarded fetal and placental growth but did not affect survival. The rat embryo is highly sensitive to elevated maternal estradiol concentrations over much of gestation. The early lethal effect implies that endogenous E2 production is carefully regulated to maintain pregnancy; the latter growth-retarding effect suggests that E2 may have a role in the normal control of fetal growth.

No abstract

No abstract

The polar bodies are derived from meiotic divisions during oogenesis and are contained together with the oocyte within the zona pellucida. Fertilisation triggers the second meiotic division, at which time the second polar body (PB2) is formed (Hogan et al., 1986; Schatten et al., 1988; Johnson & Everitt, 1995) There is no clear evidence on the fate of the polar bodies in any mammal including the mouse, which is the commonly used research model. However, the polar bodies are generally considered as waste material, and therefore not essential to embryo development. In recent years the polar bodies have gained prominence as they have been used in humans for pre-implantation genetic diagnostic purposes (PGD), of single gene disorders, such as determining whether an embryo may have inherited the cystic fibrosis allele from its mother (Munne et al., 1995; Strom et al., 1998; Rechitsky et al., 2000). PB2 also has a potential use in cloning, for the harvesting of stem cells. Wakayama et al. (1997) have shown that PB2 has the same genetic potential as the female pronuclei and can be used for the production of normal offspring in mice. The successful use of PB2 for these purposes is dependent on its age, for its longevity, rate and nature of degeneration has yet to be determined. While there is little doubt that the first polar body (PB1) experiences a necrotic fate, the same cannot be said for PB2, which may experience an apoptotic fate. Furthermore if PB2 experiences an apoptotic fate rather than a necrotic one, it would not only be the earliest evidence of apoptosis in a mammal but also provide an excellent research model for the study of apoptosis.