Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Fas^lpr/lpr mice

Abstract

Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of "oocyte cumulus complexes" found in the ampulla was macroscopically counted, and that of "ovulated oocytes" was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.

MRL/MpJ mice produce more oocytes and exhibit impaired fertilisation and accelerated luteinisation after superovulation treatment

“…Consistent with our previous findings (Hosotani et al 2018) and other reports (Yokoyama and Hioki 1990), in this study MRL/MpJ mice ovulated significantly more COCs than did C57BL/6 mice after superovulation treatment. MRL/MpJ mice generated approximately 70 oocytes after the injection of PMSG and hCG, and approximately 10 oocytes in the normal oestrous cycle.…”

“…Therefore, we hypothesised that these unique ovarian phenotypes of MRL/MpJ mice may be due to a high sensitivity to superovulation treatment and/or faster luteinisation. Indeed, in support of the latter hypothesis, the sum of the histological number of ovulated oocytes and corpora lutea (CL) was comparable to the number of COCs in the ampulla of oviducts from MRL/MpJ mice (Hosotani et al 2018).…”

“…The ovaries were fixed with 4% paraformaldehyde at 4°C overnight, embedded in paraffin and cut into 10-µm serial sections. Using serial hematoxylin-eosin (HE)-stained sections, the number of antral follicles, ruptured follicles, corpora haemorrhagica and CL was counted manually by histological observation, as described previously (Hosotani et al 2018).…”

“…Surprisingly, the number of COCs in the ampulla of oviducts exceeded the number of 'ovulated oocytes' in the ovaries of MRL/MpJ mice, as determined histologically by counting the total number of ruptured follicles, corpora haemorrhagica and the follicular antrum containing no oocytes. These results suggest that the oocyte pick-up rate in MRL/MpJ mice was over 100% (Hosotani et al 2018). Therefore, we hypothesised that these unique ovarian phenotypes of MRL/MpJ mice may be due to a high sensitivity to superovulation treatment and/or faster luteinisation.…”

“…Previously, we established a novel method to evaluate the pick-up efficiency of ovulated oocytes in mouse oviducts (Hosotani et al 2018). Using this method, we found that MRL/MpJ mice subjected to hormonal superovulation produced a markedly larger number of cumulusoocyte complexes (COCs) than did C57BL/6 mice at 3 months of age (Hosotani et al 2018).…”