Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure.

Abdeljabar El Andaloussi,Ayman Al-Hendy,Amero Amer,Prosper Igboeli

doi:10.3390/biomedicines6030093

Abdeljabar El Andaloussi, Ayman Al-Hendy + Show 2 more

Open Access

https://doi.org/10.3390/biomedicines6030093

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Abstract

Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. In addition, CTX decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR (steroidogenic acute regulatory protein), and Connexin-43 protein expression in the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (p < 0.05). When both CTX and untreated control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (p < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells.

Highlights

600,000 American women are diagnosed with cancer each year, of whom 8.0% are of pre-reproductive age [1]
We found that transfusion of autologous PBMC to mice with chemotherapy induced premature ovarian failure (POF) was very effective at restoring fertility
Injection, a period corresponding to Proestrus, the stage of the estrous cycle characterized by enhanced folliculogenesis and estrogen biosynthesis, mice were anesthetized with isoflurane and the abdominal contents exposed via mid-ventral laparotomy to facilitate blood collection from the inferior vena cava and excision of ovaries

Summary

Introduction

600,000 American women are diagnosed with cancer each year, of whom 8.0% are of pre-reproductive age [1]. Cancer incidence has been increasing annually, earlier detection and more effective treatments have reduced mortalities by approximately 1.0% per annum since the. Chemotherapy (CXT) is the most common treatment modality used in cancer patients followed by surgery, radiotherapy, and other more specialized treatment [3]. Premature ovarian failure (POF) is a common long-term consequence of CTX and radiotherapy [4,5]. As survival rates for young female cancer patients continue to improve, protection against iatrogenic POF caused by CTX and preserving future fertility become central in planning, management and outcome [6].

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