Anthony L. Komaroff, MD reviewing Kano M et al. Proc Natl Acad Sci U S A 2017 Feb 28. Woodruff TK. Proc Natl Acad Sci U S A 2017 Feb 28.

Müllerian inhibiting substance is being explored as a reversible protective agent.

At birth, every female infant has a stock of quiescent primordial ovarian follicles, which are gradually depleted during the woman's reproductive years. Chemotherapy damages those follicles and can prevent them from activating and ovulating later in life.

A research team has discovered that, in mice, long-term exposure to Müllerian inhibiting substance (MIS) results in complete arrest of follicle development: Ovarian reserve remains stable, and contraception is induced for as long as high blood levels of MIS persist. To determine if supraphysiological levels of MIS would reversibly protect ovarian reserve in young female mice, researchers first exposed the mice to high levels of MIS, either through gene therapy that produced a constant source or through chronic infusion. The treated mice then received one of three oncologic agents — carboplatin, doxorubicin, or cyclophosphamide — that typically cause serious ovarian damage.

Pretreatment with MIS protected many primordial follicles from damage by oncotherapy. Ending MIS treatment was followed by normal activation of ovarian follicles.

CITATION(S):

Kano M et al. AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy. Proc Natl Acad Sci U S A 2017 Feb 28; 114:E1688.

Woodruff TK.A win-win for women's reproductive health: A nonsteroidal contraceptive and fertoprotective neoadjuvant. Proc Natl Acad Sci U S A 2017 Feb 28; 114:2101. 

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