Next Generation

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Science  23 Aug 2013:
Vol. 341, Issue 6148, pp. 821
DOI: 10.1126/science.341.6148.821-c

Many signaling factors and tissues interact to enable successful fertilization, gestation, and delivery. Failure of any one of a number of these elements can result in a failed pregnancy. The Lrh-1 gene encodes an orphan nuclear receptor, liver receptor homolog-1. When Zhang et al. knocked out this gene in the ovarian follicle of mice, females displayed regular mating and successful ovulation but were infertile. Analysis of the corpora lutea of these mice showed that transcripts from genes involved in steroidogenesis decreased after ovarian stimulation, and hence progesterone levels were reduced, with resultant implantation failure. The defect in implantation could be rescued by the administration of progesterone, but other problems remained, including an improper spacing of embryos and differences in fetoplacental size. In addition to being expressed in the corpus luteum, Lrh-1 is also expressed in the endometrium of mice and humans. Without it, abnormal expression of endometrial genes results in uterine dysfunction and aberrant gestation. This work shows the critical roles that Lrh-1 plays in successful pregnancy via activities in both luteal function for decidualization and the formation of the placenta.

Nat. Med. 19, 1061 (2013).

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