Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

Abstract

Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders.

Estrogens maintain skeletal muscle and satellite cell functions

“…1B, C and D) (Kitajima et al 2015). As a decrease in uterine size and increase in body weight are typical phenotypes of an estrogendeficient state (Jansson et al 2006), our ovariectomy-induced estrogen-deficient model was established successfully.…”

“…Six-week-old female C57BL/6 mice (Charles River Laboratories) were ovariectomized under anesthesia. The slow-release 17β-estradiol pellets were implanted at the same time as OVX for estrogen replacement as described previously (Kitajima et al 2015). Sham-operated mice were used as a control.…”

Sexual dimorphisms in adult human neural, mesoderm‐derived, and neural crest‐derived stem cells

“…Blankenhorn et al [24] reported a faster and more complete regrowth of cartilage, skin, and hair follicles in an ear pinna regeneration model in female mice compared to their male counterparts. Reasonable underlying mechanisms could be either NF-jB-mediated osteoclastic activity, which is induced by increased levels of TNFa after ovariectomy [27] or loss of MSCs [28]. Interestingly, in sheep and rat models ovariectomy was also reported to closely mimic osteoporosis, a multifactorial disease frequently observed in postmenopausal women [25,26].…”

“…Interestingly, in sheep and rat models ovariectomy was also reported to closely mimic osteoporosis, a multifactorial disease frequently observed in postmenopausal women [25,26]. Reasonable underlying mechanisms could be either NF-jB-mediated osteoclastic activity, which is induced by increased levels of TNFa after ovariectomy [27] or loss of MSCs [28]. In line with the findings by Blankenhorn et al, reperfusion of infarcted rat hearts with female MSCs resulted in significantly increased recovery of left ventricular developed pressure compared to infarcted hearts treated with male MSCs [13].…”

Retinoic acid and 17β‐estradiol improve male germ cell differentiation from mouse‐induced pluripotent stem cells

“…Researches indicated that co‐culture of neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones could increase mESCs‐derived PGCLCs for repeating the entire male gametogenesis in vitro (Zhou et al, ). Reports indicated that oestrogen contributes critically to regulate differentiation and survival of tissue‐specific stem or progenitor cells or embryonic stem cells (Kitajima et al, ). Moreover, it is important in terms of signalling to the rapid growth of PGC in vitro (Eskandari et al, ).…”