title: Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure.
abstract: Elevated levels of LH have been associated with infertility and miscarriage in women. Previously, we have reported generating a transgenic mouse model that hypersecretes LH. Female transgenics exhibit extensive pathology including enlarged, cystic, and hemorrhagic ovaries; elevated testosterone:estradiol ratios; and infertility primarily due to anovulation. Here we show that anovulation can be reversed in transgenics and that, despite development within a pathological ovary, oocytes from transgenics are remarkably healthy. Fertilized ova from transgenics are capable of normal development to term when transferred into nontransgenic pseudopregnant recipients. However, reciprocal transfers of nontransgenic embryos into transgenic recipients failed due to lack of uterine receptivity. In addition, while superovulated and mated transgenics appear to have normal early pregnancy, embryos are resorbed at midgestation due to maternal hormonal defects. Transgenic infertility can be rescued by ovariectomy with progesterone and estradiol replacement. These studies are particularly intriguing in light of data indicating an increased rate of miscarriage among women undergoing infertility treatments who are diagnosed with polycystic ovarian syndrome.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4965, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Mann
authors.forename: R A
authors.initials: RA
authors.lastname: Keri
authors.forename: J H
authors.initials: JH
authors.lastname: Nilson
mesh_terms: D000818:Animals; D000858:Anovulation / Q000150:complications*; D005260:Female; D005327:Fetal Resorption / Q000209:etiology*; D007247:Infertility, Female / Q000209:etiology*; D007986:Luteinizing Hormone / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000473:pathology; D011247:Pregnancy; D014599:Uterus / Q000502:physiology*
chemical_list: D007986:Luteinizing Hormone