Pathophysiology and Management of Classic Galactosemic Primary Ovarian Insufficiency

Classic Galactosemia is an inborn error of carbohydrate metabolism associated with early-onset primary ovarian insufficiency (POI) in young women. Our understanding of the consequences of galactosemia upon fertility and fecundity of affected women is expanding, but there are important remaining gaps in our knowledge and tools for management, and a need for continued dialogue so that the special features of the condition can be better managed. Here, we review galactosemic POI and its reproductive endocrinological clinical sequelae and summarize current best clinical practices for its management. Special consideration is given to the very early-onset nature of the condition in the pediatric/adolescent patient. Afterward, we summarize our current understanding of the reproductive pathophysiology of galactosemia, including the potential action of toxic galactose metabolites upon the ovary. Our work establishing that ovarian cellular stress reminiscent of endoplasmic reticulum (ER) stress is present in a mouse model of galactosemia, as well as work by other groups, are summarized.

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Uterine Cells Improved Ovarian Function in a Murine Model of Ovarian Insufficiency

Reproductive Sciences ◽

10.1177/1933719119875818 ◽

2019 ◽

Vol 26 (12) ◽

pp. 1633-1639 ◽

Cited By ~ 1

Author(s):

Andres Reig ◽

Ramanaiah Mamillapalli ◽

Alexis Coolidge ◽

Joshua Johnson ◽

Hugh S. Taylor

Keyword(s):

Stem Cells ◽

Young Women ◽

Murine Model ◽

Ovarian Function ◽

Fluorescent Protein ◽

Primary Ovarian Insufficiency ◽

Age Group ◽

Ovarian Dysfunction ◽

Ovarian Insufficiency ◽

Green Fluorescent

Primary ovarian insufficiency (POI) is defined as ovarian dysfunction in women younger than 40 years. It affects 1% of the women in this age-group and can occur iatrogenically after chemotherapy. Stem cells have been used in attempt to restore ovarian function in POI. In particular, endometrial mesenchymal stem cells (eMSCs) are easily obtainable in humans and have shown great potential for regenerative medicine. Here, we studied the potential for uterine cell (UC) suspensions containing eMSCs to improve ovarian function in a murine model of chemotherapy-induced POI. Green fluorescent protein (GFP)-labeled UC or phosphate-buffered solution (PBS) was delivered intravenously after chemotherapy. There was a significant increase in oocytes production and serum anti-Müllerian hormone concentrations after 6 weeks, as well as a 19% higher body mass in UC-treated mice. Similarly, we observed an increased number of pups in mice treated with UC than in mice treated with PBS. None of the oocytes or pups incorporated GFP, suggesting that there was no contribution of these stem cells to the oocyte pool. We conclude that treatment with UC indirectly improved ovarian function in mice with chemotherapy-induced POI. Furthermore, our study suggests that endometrial stem cell therapy may be beneficial to young women who undergo ovotoxic chemotherapy.

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Insights into the Pathophysiology of Infertility in Females with Classical Galactosaemia

International Journal of Molecular Sciences ◽

10.3390/ijms20205236 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5236 ◽

Cited By ~ 1

Author(s):

Zaza Abidin ◽

Eileen P. Treacy

Keyword(s):

Inborn Error ◽

Primary Ovarian Insufficiency ◽

Future Prospects ◽

Ovarian Dysfunction ◽

Galactose Metabolism ◽

Ovarian Insufficiency ◽

New Horizons ◽

Classical Galactosaemia ◽

Rare Inborn Error

Classical galactosaemia (CG) (OMIM 230400) is a rare inborn error of galactose metabolism caused by the deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT, EC 2.7.7.12). Primary ovarian insufficiency (POI) is the most common long-term complication experienced by females with CG, presenting with hypergonadotrophic hypoestrogenic infertility affecting at least 80% of females despite new-born screening and lifelong galactose dietary restriction. In this review, we describe the hypothesized pathophysiology of POI from CG, implications of timing of the ovarian dysfunction, and the new horizons and future prospects for treatments and fertility preservation.

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