Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury

TLDR

Chemotherapy destroys primordial follicles and can cause ovarian atrophy, and while apoptosis is a known mechanism, other pathways may also contribute. The study aimed to assess ovarian damage after non‑sterilizing chemotherapy doses by evaluating pathological changes in cryopreserved ovarian tissue and to explore whether these changes contribute to ovarian aging. A blind study examined ovarian tissue from 35 young cancer patients (17 previously exposed to non‑sterilizing chemotherapy and 18 unexposed) to identify histopathological alterations. Exposed patients exhibited cortical blood‑vessel damage, small‑vessel proliferation, and focal fibrosis with follicle loss (sensitivity 76 %, PPV 75 % for <37 yr), while similar changes were seen in older unexposed patients, indicating vascular injury and fibrosis as additional chemotherapy‑induced ovarian damage mechanisms.

Abstract

Chemotherapy destroys primordial follicles and can lead to ovarian atrophy. Although reports indicate that apoptosis is the mechanism responsible for follicle loss, additional pathways can be involved. This study investigates the damage in human ovaries after administration of non-sterilizing doses of chemotherapy.In a blind study, pathological changes in ovarian tissue harvested for cryopreservation were evaluated. The study group comprised young non-sterile cancer patients, previously exposed to chemotherapy who were (mean +/- SD), when compared with non-exposed patients.Thirty-five cancer patients aged 28.7 +/- 6.74; 17 were previously exposed to non-sterilizing chemotherapy and 18 were not. In all samples, primordial follicles were present. In previously exposed patients, damage to cortical blood vessel and proliferation of small vessels was observed. The cortex showed focal areas of fibrosis with disappearance of follicles (sensitivity 76%, positive predictive value 75% for <37 years old patients). Older patients, not exposed to chemotherapy (5/7) showed similar pathological changes.Injury to blood vessels and focal ovarian cortical fibrosis are aspects of ovarian damage caused by chemotherapy. These findings indicate a potential additional mechanism of damage to the direct apoptotic effect of chemotherapy on follicles. The possibility that these changes are involved in ageing ovaries should be further investigated.