Table 2.
Knockout/overexpression studies of Hippo pathway core components and ovarian phenotypes
| Study (first author, year) | Model system | Gene targeted | Overexpression or knockout | Findings |
|---|---|---|---|---|
| Fu et al., 2014 | KGN cell line | YAP1 | OE | Increase in granulosa cell proliferation and migration |
| KO | Inhibition of cell proliferation; changes in cell morphology | |||
| Ye et al., 2017 | Cyclophosphamide (CPA)-induced infertile mouse model | Yap1 | OE | Increased follicle number, litter size/birth rate, and ovarian surface epithelium thickness |
| KO | Decreased follicle number and pup birthrate | |||
| He et al., 2019 | Primary human ovarian surface epithelium cells | YAP1 | OE | Increase in cell proliferation; eventual cell senescence |
| KO | No changes in cell proliferation | |||
| TAZ | KO | No changes in cell proliferation | ||
| YAP1/TAZ | KO | Decrease in cell number | ||
| LATS2 | KO | Increase in cell proliferation; loss of cell senescence | ||
| Lv et al., 2019 | Foxl2-cre; Yap1fl/fl mouse model | Yap1 | KO | Decrease in ovarian follicle number/formation; decrease in ovarian size; increased number of atretic follicles; decreased litter size |
| Mouse model—in vitro ovary culture | Yap1 | Inhibition via VP | Disruption of follicle formation | |
| Mouse model—in vivo | Yap1 | Inhibition via VP | Reduced corpora lutea; increased granulosa cell apoptosis | |
| Plewes et al., 2019 | Primary bovine granulosa cells | YAP1 | KO | Reduced granulosa cell proliferation |
| TAZ | KO | Decreased granulosa cell proliferation | ||
| Hu et al., 2019 | Mouse model—in vitro ovary culture | Yap1 | OE | Decrease in primordial follicle number; increase in primary follicle number |
| KO | Increase in primordial follicle number; decrease in primary follicle number | |||
| Hu et al., 2019 | Tri-ortho-cresyl phosphate (TOCP) exposed mouse model | Yap1 | OE | Increase in follicle numbers; decreased atretic follicles; increased fertility |
| Lv et al., 2020 | Primary human granulosa cells from IVF patients | YAP1 | OE | Increased granulosa cell proliferation and growth; loss of granulosa cell identity |
| KO | Decreased granulosa cell proliferation and growth; increased cell apoptosis | |||
| KGN cell line | YAP1 | OE | Promotion of cell cycle progression; decrease in apoptotic cells; loss of granulosa cell identity | |
| KO | Reduced proliferation; increased apoptosis | |||
| HGrC1 cell line | YAP1 | OE | Increased granulosa cell proliferation and growth; decreased apoptosis; loss of granulosa cell identity | |
| KO | Suppressed granulosa cell proliferation | |||
| St John et al., 1999 | Lats1 -/- mouse model | Lats1 | KO | Reduced follicle number; disruption in ovulation |
| Sun et al., 2015 | Lats1 -/- mouse model | Lats1 | KO | Abnormal follicle development; development of ovarian cysts; increased germ cell apoptosis |
| Tsoi et al., 2019 | Lats1 fl/fl ; Lats2fl/fl; Cyp19a1-cre mouse model | Lats1/2 | KO | Enlargement of the ovary; infertility; loss of granulosa cell identity |
| Lats1 fl/fl ; Lats2fl/fl; Cyp19a1-cre mouse isolated granulosa cells | Lats1/2 | KO | Loss of granulosa cell identity and function | |
| St Jean et al., 2019 | Lats1 fl/fl ; Lats2fl/fl; Amhr2-cre mouse model | Lats1/2 | KO | Reduced follicle number; alterations in granulosa cell morphology and identity; thickening of the ovarian surface epithelium |
| Sun et al., 2021 | Primary hen granulosa cells | LATS2 | OE | Decrease in granulosa cell proliferation |
| KO | Increase in granulosa cell proliferation | |||
| Lyu et al., 2016 | Primary hen granulosa cells | SAV1 | OE | Decrease in granulosa cell proliferation |
| KO | Increase in granulosa cell proliferation |
Abbreviations: KO, knockout; OE, overexpression; VP, verteporfin.