Abstract
Macroheterogeneity in follicle-stimulating hormone (FSH) β-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is the abundant and more bioactive form in pituitaries of females under 35 years of age, whereas fully glycosylated FSH24 is less bioactive and increases with age. To investigate whether the shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, the direct effects of FSH glycoforms on folliculogenesis and oocyte quality were determined using an encapsulated in vitro mouse follicle growth system. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion and oocyte quality compared with FSH24 (10 ng/ml) treatment. FSH21 enhanced establishment of transzonal projections, gap junctions and cell-to-cell communication within 24 h in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. Our data indicate that FSH21 promotes folliculogenesis and oocyte quality in vitro by increasing cell-to-cell communication early in folliculogenesis, and that the shift in in vivo abundance from FSH21 to FSH24 with reproductive aging may contribute to the age-dependent decline in oocyte quality.
| Original language | English (US) |
|---|---|
| Article number | dev202170 |
| Journal | Development (Cambridge) |
| Volume | 150 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 2023 |
Funding
This work was supported in part by the National Institutes of Health (NIH) (HD103384, AG029531 and AG062319 to T.R.K.), The Makowski Family Endowment, The Gates Grubstake Award from the University of Colorado Anschutz Medical Campus and the Gonadotropin Research Fund (Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus) (T.R.K.). Deposited in PMC for release after 12 months. We acknowledge Prianka H. Hashim and Kathryn Trotter for their help with follicle isolation for RNA-seq experiments, and James Eudy and the Nebraska University Medical Center DNA sequencing core for help with RNA-seq experiments. The University of Nebraska DNA Sequencing Core was supported in part by the National Institute for General Medical Science (NIGMS) INBRE - P20GM103427-19 grant as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30 CA036727. The Bioinformatics and Systems Biology Core (BSBC) received partial support from NIH awards (P20GM103427, P30CA036727, U54GM115458). We acknowledge Prianka H. Hashim and Kathryn Trotter for their help with follicle isolation for RNA-seq experiments, and James Eudy and the Nebraska University Medical Center DNA sequencing core for help with RNA-seq experiments. The University of Nebraska DNA Sequencing Core was supported in part by the National Institute for General Medical Science (NIGMS) INBRE - P20GM103427-19 grant as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30 CA036727. The Bioinformatics and Systems Biology Core (BSBC) received partial support from NIH awards (P20GM103427, P30CA036727, U54GM115458). This work was supported in part by the National Institutes of Health (NIH) (HD103384, AG029531 and AG062319 to T.R.K.), The Makowski Family Endowment, The Gates Grubstake Award from the University of Colorado Anschutz Medical Campus and the Gonadotropin Research Fund (Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus) (T.R.K.). Deposited in PMC for release after 12 months.
Keywords
- FSH glycoform
- Mouse
- Oocyte quality
- Ovarian follicle
- Transzonal projections
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology