REVIEWS AND COMMENTARY on recent literature in reproductive medicine and biology
The staff of THE REPRODUCTIVE TIMES here offers commentaries on recently published articles, primarily chosen for educational values—in the positive but also in the negative—for clinical purposes, and for their potential translational values to clinical medicine when addressing basic science in reproductive medicine and biology.
Is cancer increased in women with primary ovarian insufficiency (POI)?
Both POI and cancer have been associated with DNA damage/repair gene variants. In a population-based case-control study investigators from the University of Utah now report that POI and certain reproductive cancers share common genetic risk. The cancers involved were breast cancer and, to a lesser degree, ovarian cancer. Relatives were associated with colon and prostate cancers. The authors concluded that the common risk between POI and primarily reproductive cancers may have relevance to postmenopausal hormone replacement therapy.
Reference
1. Allen-Brady et al., J Clin Endocrinol Metab 2024; 12:dgae480. doi: 10.1210/clinem/dgae480. Online ahead of print.
Does noise and air pollution affect fertility?
These were the questions Danish investigators recently explored in the British Medical journal (BMJ) and yes, they found evidence that the risk of infertility appears associated with long-term exposure to traffic noise as well as air pollution (1). Specifically, they reported the following: (i) Particulate air pollution was associated with an increased risk of infertility in men. (ii) Traffic noise was associated with a higher risk of infertility in women above age 35 and, likely, men above age 37. If confirmed, it of course raises the question, what could be done about it?
Reference
1. Sørensen et al., BMJ 2024;386:e080664
More animal evidence in a mouse model that DHEA supplementation improves ovarian function
Though by now used in fertility practice worldwide, DHEA as a fertility enhancer in infertile women has remained controversial. The principal reason has been the absence of well-powered and designed prospectively randomized studies, as attempts to execute such studies repeatedly have run into recruitment problems because infertile women—understandably—often are reluctant to be randomized to placebo for prolonged time periods. The use of DHEA has, therefore, primarily relied on either underpowered and poorly controlled small clinical trials or studies of lower evidence levels.
What is, however, often overlooked when this issue comes up in discussion, is the fact that animal models, small and large, have by now not only clearly defined why good androgen levels are essential for good follicle growth and maturation especially at small growing stages between primary and small-antral follicle stages but have also demonstrated improved ovarian function after androgen supplementation in androgen-deficient animals.
Yet another such study was recently published by Chinese investigators in Reproductive Biomedicine Online in which DHEA (the precursor of testosterone) was demonstrated to promote angiogenesis and improved ovarian function in a rat model premature ovarian insufficiency. The study moreover also demonstrated that this effect was achieved by upregulating HIF-1 alpha/VEGF signaling (1).
Reference
1. Zhao et al., Reprod Biomed Online 2024;49(3):103914
Preventing chemotherapy-induced ovarian damage
The literature has suggested various modalities to minimize or even completely prevent chemotherapy-induced ovarian damage. Now investigators from the University of Chicago reported in a mouse model that pretreatment of ovaries with mesenchymal stem cell exosomes prevents chemotherapy-induced ovarian damage (1).
The idea for this study came from the observation that mesenchymal stem cells and exosomes derived from them may be able to restore ovarian function in preclinical models of primary ovarian insufficiency (POI) by restoring damaged cells and inhibiting apoptosis. Whether these observations were, however, also applicable to preventing ovarian damage was unknown. The authors concluded that using exosomes from mesenchymal stem cells could represent a simple new treatment of ovaries to prevent chemotherapy damage.
Reference
1. Park, eta., Am J Obstet Gynecol2024;231:111.e1-e18
Some basic news on PCOS
It is widely believed that ca. 20% of all women suffer from one form or the other form of PCOS. Despite this very obvious importance, progress in our understanding of PCOS has been painfully slow. Every piece of new scientific information that can contribute to a better understanding, therefore, is valuable. British and Australian investigators now published a preprint in eLife which may do this (1). As it is only a “reviewed preprint” without revisions, the data should be consumed with caution, but we are noting the paper here because of the potential importance of reported findings. The study also involved mouse models and “mice are not men” (in this case women).
It is also widely believed that in PCOS the so-called arcuate kisspeptin (ARNKISS) neurons making up the GnRH pulse generator are dysfunctional. Using highly sophisticated methods and technologies, the authors in this paper in two different mouse models attempted to define the generator’s behavior. What they discovered is a complex phenotype demonstrating various deficits at multiple levels of the hypothalamic-pituitary axis. In other words, PCOS is a highly variable condition and one, indeed, has to start asking whether it isn’t time to no longer consider it one condition.
Reference
1. Zhou et al., https:/doi.org/10.7554/eLife.97179.1