Fig. 1

Stem cell kinetics in adult ovaries and uterus. A Sheep ovarian stem cells isolated from the ovary surface epithelium are of two distinct sizes and show asymmetrical and symmetrical cell divisions and clonal expansion [14, 15]. These cells were immuno-stained for FSHR. B Two populations of stem cells were clearly visualized in the mouse uterus at higher magnification. Asymmetrical (red arrow), symmetrical (green arrow) and clonal expansion showing distinct cytoplasmic connectivity [14]. C-F Hematoxylin and Eosin stained ovary surface epithelial cells smears obtained from adult mice ovaries during different stages of estrus cycle, showing stem cells and germ cell nest (GCN) formed by clonal expansion across estrus cycle. G-J Meiotic entry marker synaptonemal complex protein 3 (SCP-3) expression in the GCN during different stages of estrus cycle. It is distinctly cytoplasmic during proestrus suggestive of an oogonial nest, punctate nuclear expression suggests leptotene stage during estrus while the typical crossover pattern during metestrus is suggestive of pachytene stage suggesting gradual maturation and meiosis in the GCN is stage specific. Ki-iii Nuclear stimulated by retinoic acid gene 8 (STRA-8) is a specific marker for pre-meiotic germ cells. SCP-3 and STRA-8 expression provide strong evidence to support neo-oogenesis in adult ovary [16]. Li-iii SCP-3 expression in DAPI stained nuclei of cells comprising a GCN. Mi-iv Co-localization of cytoplasmic OCT-4 and TEX-14 positive ring canals in an oogonial stage GCN. (N–O) GCN detected in the OSE isolated from the recipient mice upon transplantation of FACS sorted SSEA-1 + VSELs from a GFP mice. GCN developed from endogenous, tissue-resident VSELs formed SSEA-1 + GCN while the transplanted VSELs formed GFP + SSEA-1 + GCN. Note the GCN were exclusively either GFP-ve or GFP + suggesting their clonal origin [18]. If these were formed by mere aggregation of cells as commented [3], they would show a heterogenous pattern of GFP expression. P-Q Stem cells and GCN detected in 24 months old mice ovaries showing expression of mouse vasa homolog (MVH) (P) and SCP-3 (Q). These GCN in aged ovaries are blocked in development into oocytes due to age-related compromised niche as discussed [19]. Both neo-oogenesis in adult life and senescence in aged ovaries have a stem cell basis and VSELs are greatly increased in ovarian cancer [16, 19,20,21]