Increased plugging latency in cycling epiERα-/- (Esr1f/-Wnt7aCre/+) mice

Wnt7a-Cre is a commonly used for generating uterine epithelial conditional knockout mice, such as epiERα-/- (Esr1f/-Wnt7aCre/+) and epiPR-/- (Pgrf/-Wnt7aCre/+). We noticed that epiERα-/- females, but not epiPR-/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle. Vaginal cytology detected estrous cyclicity in all mice examined, although epiERα-/- mice had leukocyte dominant vaginal cytology throughout the estrous cycle and their estrous cyclicity appeared less regular. Estrous cyclicity and mating activity are regulated by the hypothalamic–pituitary–ovarian axis, in which kisspeptin plays essential roles. ERα and PR are expressed in rostral periventricular area of the ventricle (RP3V) and arcuate nucleus (ARC) kisspeptin neurons in the hypothalamus. It has been reported that Esr1f/fKiss1-Cre mice lack estrous cyclicity, while Pgrf/fKiss1-Cre mice have normal estrous cyclicity at 2 months old, and Wnt7a is highly expressed in ARC. The prolonged plugging latency in epiERα-/- mice could be contributed by the deletion of ERα in Wnt7A-positive cells in ARC. Wnt7a-Cre was also used to generate uterine epithelial RhoA deficient mice, epiRhoA-/- (RhoAf/-Wnt7aCre/+). However, both female and male RhoAf/-Wnt7aCre/+ mice had hydrocephalus and died within a few weeks old. Our observations of increased plugging latency in epiERα-/- mice and hydrocephalus in RhoAf/-Wnt7aCre/+ mice exemplify unintended neuronal gene deletion using Wnt7a-Cre for uterine epithelial-specific gene deletion.