Impact of Hyaluronidase-1 and Hyaluronidase-3 Deficiency on Mouse Female Reproduction.
Bibliographic record
Abstract
Mammalian hyaluronidases (EC 3.2.1.35) are endo-β-N-acetyl-hexosaminidases, that hydrolyze hyaluronic acid (hyaluronan), and to a lesser extent chondroitin and chondroitin sulfate, to generate mostly tetra-saccharides. In the ovary, expression of three hyaluronidases (Hyal-1, Hyal-2 and Hyal-3) has been documented and our group has recently shown that these enzymes are predominantly expressed in granulosa cells and are involved in follicular atresia. Interestingly, we found Hyal-1 to be preferentially expressed in small antral follicles of immature mice, and to be repressed in gonadotropin-responsive follicles. In addition, we showed that expression of all three hyaluronidases induced granulosa cell apoptosis via activation of the extrinsic apoptotic signaling pathway, although enzymatic activity was not required for this apoptosis induction. It is possible that a direct binding of hyaluronidases to specific protein partners would trigger the apoptotic signaling pathway. In the present work, we investigated the impact of Hyal-1 and Hyal-3 deficiency in female reproduction. Using our established mouse model for ovarian atresia (gonadotropin withdrawal by anti-eCG treatment), we showed that Hyal-1 but not Hyal-3 null mice have decreased apoptotic granulosa cells after atresia induction. Moreover, these Hyal-1 null mice (but not the Hyal-3 null animals) had increased number of retrieved oocytes after ovulation stimulation. Furthermore, young Hyal-1 null mice have significantly higher number of primordial follicles than age matched wild-type animals. Recruitment of these follicles at puberty resulted in increased number of primary and secondary follicles in 6-week-old null mice, but not in animals older than 6 months. These results indicate that Hyal-1 plays a role in the initial phase of follicle recruitment in young mice. Significantly, we observed increased levels of anti-Mullerian hormone (AMH) mRNA expression in pre-pubertal Hyal-1 null mice when compared to wild-type animals. Collectively, our findings indicate that Hyal-1 but not Hyal-3 has an important role in ovarian folliculogenesis and atresia. We suggest that induction of granulosa cell apoptosis by hyaluronidase-1 on follicles of immature mice is an important step for the control of initial primordial follicle recruitment. This enzyme might play a key role in the early phases of folliculogenesis by negatively regulating ovarian follicle growth and survival. Regulatory mechanisms involving expression of intra-ovarian factors of the TGFβ superfamily would participate in this process. Up to now, physiological roles of hyaluronidases in reproduction have been described only for testicular hyaluronidases (e.g. PH20/Spam1, Hyal-5, and Hyalp1), which have sperm-fertilizing ability by dispersing the cumulus layers of the ovulated cumulus-oocyte complex. Our results add somatic hyaluronidases as new players in ovarian folliculogenesis. Supported by NSERC (Natural Sciences and Engineering Research Council of Canada) (platform)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".