FIB’s mission is to encourage, enable, and support research aimed at alleviating human infertility, uncovering new possible pathways to control fertility, and expanding fundamental knowledge of processes that underlie human reproduction. To this end, FIB funds basic, clinical, and translational studies to enhance our understanding of normal reproduction and reproductive pathophysiology, as well as to enable the development of more effective strategies for the diagnosis, management, and prevention of conditions that compromise fertility.
Human Infertility Allele Database . This NICHD-funded resource lists experimentally validated benign and deleterious single nucleotide polymorphisms in genes associated with human infertility (site works best in Firefox and Chrome).
Some recent findings from FIB-supported researchers include the following:
- High-fat diet in polycystic ovary syndrome (PCOS) women is linked to defects in placenta. PCOS affects 5-15% of reproductive-age women in the United States, often causing subfertility because of the endocrine and metabolic dysfunction that occur with the syndrome. Dr. Antonio Frias and colleagues studied a primate (macaque) model of PCOS to examine how high levels of maternal testosterone and nutrition interact to influence the placenta. They found that a high-fat, Western-style diet (WSD) had significant deleterious effects on placental blood flow as compared to animals receiving a normal diet, while testosterone had negative effects on the formation of fetal blood vessels. The combination of WSD and high testosterone levels act through different mechanisms but, together, have large negative effects on overall placenta function. (PMID: 31180495)
- Role for miRNA in PCOS. Family studies have shown that PCOS has a genetic component, and a variation of the gene DENND1A, called DENND1A.v2, is implicated as the cause of increased androgen synthesis. In this study, Dr. Jerome Strauss and colleagues identified 18 microRNAs (miRNAs) that were differentially expressed in the ovarian hormone-producing cells of women with PCOS as compared to those of non-PCOS women. Among these, miR-130b-3p was predicted to target DENND1A. They found that decreased levels of miR-130b-3p are correlated with increased levels of DENND1A.v2, along with increased androgen synthesis. This is the first demonstration that post-transcriptional factors can also contribute to PCOS (PMID: 31184707).
- Genetic regulation of hypothalamic-pituitary-gonadal axis controls menstrual cycle length. Characteristics of the menstrual cycle, including its length, are an important index of a woman’s reproductive health. Dr. Stephanie Seminara and her colleagues performed a meta-analysis of genome-wide association data on menstrual cycle length in 44,871 women of European ancestry, and they confirmed menstrual length is partially controlled by the follicle-stimulating hormone beta subunit (FSHB). They also identified four additional novel signals in, or near, the genes encoding GNRH1 (gonadotropin-releasing hormone 1), PGR (progesterone receptor), NR5A2 (a nuclear receptor involved in cholesterol metabolism), and INS-IGF2 (isoform 2 of insulin) that contribute to the length of a menstrual cycle. These findings confirm the role of genetic variation in the hypothalamic-pituitary-gonadal axis in regulating of menstrual cycle length, and also identify potential novel local regulatory mechanisms. (PMID: 30202859)
- Primate born using sperm from frozen juvenile testicular tissue. Cancer treatment can spare a young boy’s life, at the cost of his future fertility. Currently, no options exist for fertility preservation for boys who are too young to produce sperm. Dr. Kyle Orwig and his colleagues grafted cryopreserved testicular sections taken from juvenile rhesus macaques back into the original donors after puberty. The grafts grew and made testosterone and sperm, which in one case resulted in a successful pregnancy and live birth. This is the first proof that immature testicular tissue can be preserved and used later to restore fertility. (PMID: 30898927)
- Epigenetic changes in ADAMTS linked to preterm birth. Dr. Mainigi and colleagues studied placentas from a population of women at high risk for preterm birth. Their research showed that regulation of methylation levels of members of the gene family ADAMTS, implicated in cell invasion and migration, is important in regulating early placentation and later susceptibility to preterm birth. (PMID: 30239759)