Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics in chemoresistance may provide insight into new biomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers.

Uterine leiomyosarcoma (u‐LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and patients have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, although some biomarker candidates have appeared. In 2017, The Cancer Genome Atlas (TCGA) Research Network's work on u‐LMS has confirmed mutations and deletions in RB1,TP53 and PTEN. In addition, whole‐exome sequencing of u‐LMS has confirmed and demonstrated frequent alterations in TP53,RB1, α‐thalassemia/mental retardation syndrome X‐linked (ATRX) and mediator complex subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine‐derived LMS and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX mutations can be important mechanisms in the pathogenesis of u‐LMS and are correlated with a poor prognosis. In an update based on the 2014 WHO classification, low‐grade ESS is often associated with gene rearrangement bringing about the JAZF 1‐SUZ12 (formerly JAZF1‐JJAZ1) fusion gene, whereas high‐grade ESS is associated with the YWHAE‐NUTM fusion gene. Low‐grade ESS with JAZF1 rearrangement may correlate with metastasis. However, high‐grade ESS with metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The genetic/molecular genetic aberrations in u‐LMS and ESS are reviewed, focusing on molecular biomarkers for these primary and metastatic tumors.

Background The process of follicle development is tightly regulated by pituitary gonadotropins (follicle‐stimulating hormone [FSH] and luteinizing hormone [LH]) and intraovarian regulators (eg, steroids, growth factors, and cytokines). Methods This review outlines recent findings on the mechanisms of human follicle development, based on the research on animal models such as mice, rats, cows, and sheep. Main findings Phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and anti‐Müllerian hormone are involved in primordial follicle activation during the gonadotropin‐independent phase. The intraovarian regulators, such as androgen, insulin‐like growth factor system, activin, oocyte‐derived factors (growth differentiation factor‐9 and bone morphogenetic protein 15), and gap junction membrane channel protein (connexin), play a central role in the acquisition of FSH dependence in preantral follicles during the gonadotropin‐responsive phase. Antral follicle development can be divided into FSH‐dependent growth and LH‐dependent maturation. The indispensable tetralogy for follicle selection and final maturation of antral follicles involves (a) acquisition of LH dependence, (b) greater capacity for E2 production, (c) activation of the IGF system, and (d) an antiapoptotic follicular microenvironment. Conclusion We reproductive endocrinologists should accumulate further knowledge from animal model studies to develop methods that promote early folliculogenesis and connect to subsequent gonadotropin therapy in infertile women.