Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure

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 incl uding enlarged, cystic, and hemorrhagic ovaries; elevated testosterone:estr adiol ratios; and infertility primarily due to anovulation. Here we show th at anovulation can be reversed in transgenics and that, despite development within a pathological ovary, oocytes from transgenics are remarkably healt hy. Fertilized ova from transgenics are capable of normal development to te rm when transferred into nontransgenic pseudopregnant recipients. However, reciprocal transfers of nontransgenic embryos into transgenic recipients fa iled due to lack of uterine receptivity. In addition, while superovulated a nd mated transgenics appear to have normal early pregnancy, embryos are res orbed at midgestation due to maternal hormonal defects. Transgenic infertil ity can be rescued by ovariectomy with progesterone and estradiol replaceme nt. These studies are particularly intriguing in light of data indicating a n increased rate of miscarriage among women undergoing infertility treatmen ts who are diagnosed with polycystic ovarian syndrome.