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 1a-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 CI. 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 micrograms 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.
Pomp
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Department of Animal Science, Oklahoma State University, Stillwater 74078.
Geisert
R D
RD
Durham
C M
CM
Murray
J D
JD
D000818:Animals; D003001:Cloning, Molecular; D003340:Corpus Luteum Maintenance / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D005260:Female; D013006:Growth Hormone / Q000235:genetics* / Q000502:physiology; D007247:Infertility, Female / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007774:Lactation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008668:Metallothionein / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D012756:Sheep
D011374:Progesterone; D011388:Prolactin; D013006:Growth Hormone; D008668:Metallothionein