Altered ciliary morphofunction in the oviductal infundibulum of systemic autoimmune disease-prone MRL/MpJ-Faslpr/lpr mice

Abstract

According to our previous reports, impaired oocyte pickup was observed in the oviductal infundibulum of autoimmune disease (AD) mouse model, suggesting a relationship between female infertility and AD. This study examined the relationship between AD and infundibulum morphofunction by focusing on the epithelial cilia. Healthy MRL/MpJ and AD-prone MRL/MpJ-Fas lpr/lpr mice were examined at 3 and 6 months of age, representing early and late disease stages, respectively. Oocyte pickup indices decreased with AD progression indicated by splenomegaly, autoantibody production, and increased T-cell counts of infundibulum mucosa in MRL/MpJ-Fas lpr/lpr mice. Ciliary beating frequency (CBF) and height in the infundibulum were faster and higher in MRL/MpJ-Fas lpr/lpr mice than in MRL/MpJ mice at the early AD stages, although the absolute CBF values were lower at the late AD stage. At late stage, ciliary height did not differ between mouse lines, but the morphological index of cilia beating direction indicated randomized patterns in MRL/MpJ-Fas lpr/lpr mice. The tracheal mucosa was also examined as a representative example of cilia morphology; its CBF decreased at late AD stage in MRL/MpJ-Fas lpr/lpr , however, there were no AD-related morphological changes. Our results demonstrate altered cilia motility in systemic and reproductive organs, with such morphological changes of the infundibulum likely impairing function, including oocyte pickup .

The histopathological features of the surgical endometriosis model using systemic autoimmune disease-prone mice

“…As reported in previous studies [16,17], MRL/lpr mice showed significant splenomegaly at both 3 and 6 months of age and exacerbated severe systemic autoimmune disease at 6 months of age when compared to MRL/+ mice. Although MRL/lpr mice exhibited systemic autoimmune abnormalities, the appearance rate of endometriosis in MRL/lpr mice at 6 months of age showed no differences between those in MRL/+ mice and MRL/lpr mice at 3 months of age.…”

Oocyte cumulus complex quality and oviduct transportation velocity in systemic autoimmune disease model mice

“…Previous studies have reported that autoimmune disease is more severely exacerbated in female lpr mice at six months of age compared with those at three months of age. 5,6 The mice were housed in groups in plastic cages at 18°C–26°C under a 12-h light/dark cycle with free access to a commercial diet and water. Pregnant mare serum gonadotropin (PMSG, ASKA Animal Health Co., Ltd., Tokyo, Japan) was injected intraperitoneally into the mice (200 µL of 37.5 IU/mL gonadotropin per mouse).…”

“…MRL/MpJ- Fas lpr/lpr (lpr) mice are models of severe systemic autoimmune disease and show abnormalities in female reproductive function due to local inflammation in the ovary and oviduct, including premature ovarian failure, decreased number of ovulations, oocyte pick-up dysfunction, and abnormal morphofunction of ciliated epithelial cells. 4 –6 In the infundibulum of lpr mice, a decreased number of ciliated epithelial cells, elongation of cilia, and slow and randomized oriented ciliary beating are involved in oocyte pick-up dysfunction. 5,6 However, whether the quality of cumulus cells affects the properties of oocyte transportation in lpr mice has not been investigated.…”

Anatomy and histology of the foramen of ovarian bursa opening to the peritoneal cavity and its changes in autoimmune disease‐prone mice

“…Female B6, MRL/+, and MRL/lpr mice at 3 and 6 months of age were obtained from Japan SLC, Inc. Previous studies reported that autoimmune disease is severely exacerbated in female MRL/lpr mice at 6 months of age compared with its severity at 3 months of age (Hosotani et al, 2018(Hosotani et al, , 2020. The mice were housed in groups within plastic cages at 18-26°C, under a 12-h light/dark cycle and had free access to a commercial diet and water.…”