RESCUE OF PREGNANCY AND MAINTENANCE OF CORPORA-LUTEA IN INFERTILE TRANSGENIC MICE EXPRESSING AN OVINE METALLOTHIONEIN 1A OVINE GROWTH-HORMONE FUSION GENE

Transgenic female mice expressing a temporally regulatable ovine metallothionein la-ovine growth hormone (oMT1a-oGH) fusion gene can cycle, mate, and support early embryonic development; but they fail to maintain pregnancy or, in most cases, to exhibit signs of pseudopregnancy. The present study was designed to determine whether or not the infertility of oMT1a-oGH transgenic female mice is due to luteal insufficiency. A series of five experiments was conducted in which various hormonal therapies were utilized in an attempt to overcome this infertility. Provision of 1 mg progesterone to oMT1a-oGH females from Days 1 to 17 of gestation rescued pregnancy in 19 of 20 females with an increased mean litter size (P < 0.01) compared to that of wild-type control females. Supplementation with progesterone also appeared on the basis of gross anatomical appearance to maintain CL. Provision of 2 mg progesterone in combination with 25 ng estradiol-17 beta from Days 4 to 17 rescued pregnancy in 14 of 24 oMT1a-oGH females, while provision of 100 or 25 pg ovine prolactin from Days 3 to 17 failed to overcome oMT1a-oGH infertility. Transgenic females with rescued pregnancies lactated and raised heavier pups than wild-type females by Day 15 postnatal (P < 0.05). Results indicate that infertility of oMT1a-oGH transgenic mice is caused by luteal insufficiency. Supplementation of transgenic females with progesterone appeared to maintain morphologically normal CL and pregnancy with subsequently increased litter size and normal lactation.