
The rete ovarii is a complex, multi-regional epithelial structure directly connected to the ovary that plays an important role in ovary development and homeostasis through secretion of proteins into the ovary.


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The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

### Competing Interest Statement

The authors have declared no competing interest.

Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

characterization-of-the-rete-ovarii-a-secretory-appendage-of-the-ovary-with-potential-roles-in-ovarian-function


Characterization of the Rete Ovarii: A Secretory Appendage of the Ovary with Potential Roles in Ovarian Function


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Epididymal proteins CRISP1 and CRISP3 are critical for maintaining sperm DNA integrity, which is essential for proper early embryo development.


Numerous reports show that the epididymis plays a key role in the acquisition of sperm fertilizing ability but less information exists on its contribution to embryo development. Evidence from our laboratory showed that mammalian CRISP (Cysteine-Rich Secretory Proteins), known to be expressed in the epididymis, to regulate calcium (Ca2+) channels and to participate in fertilization, may also be relevant for embryo development. More specifically, we found that males with simultaneous mutations in Crisp1 and Crisp3 genes exhibited normal in vivo fertilization but impaired embryo development. In the present work, aimed to investigate the mechanisms underlying this reproductive phenotype, we observed that embryo development failure was not due to delayed fertilization as no differences in sperm transport within the female tract nor in in vivo fertilization were found shortly after mating. The observation that impaired embryo development was also found in eggs fertilized by epididymal sperm either after uterine insemination or in vitro fertilization, revealed that the defects were already present at epididymal level. Of note, eggs fertilized in vitro by mutant sperm exhibited impaired meiotic resumption not due to defects in Ca2+oscillations during egg activation, prompting us to examine potential sperm DNA defects. Interestingly, higher levels of both DNA fragmentation and intracellular Ca2+ were observed for mutant than for control epididymal sperm, supporting sperm DNA damage, likely linked to a Ca2+ dysregulation, as the main responsible for the early development failure of mutant males. Together, our results support the contribution of the epididymis beyond fertilization, identifying CRISP1 and CRISP3 as novel male factors relevant for DNA integrity and early embryo development. Given the existence of human functional homologues of CRISP and the incidence of DNA fragmentation in infertile men, we believe these findings not only provide relevant information on the impact of epididymal factors on embryonic development but will also contribute to a better understanding, diagnosis and treatment of human infertility.

### Competing Interest Statement

The authors have declared no competing interest.

Contribution of the epididymis beyond fertilization: relevance of CRISP1 and CRISP3 for sperm DNA integrity and early embryo development

contribution-of-the-epididymis-to-sperm-dna-integrity-and-early-embryo-development-the-relevance-of-crisp1-and-crisp3-proteins


Contribution of the Epididymis to Sperm DNA Integrity and Early Embryo Development: The Relevance of CRISP1 and CRISP3 Proteins



The X-linked miR-506 family miRNAs, which are predominantly expressed in spermatogenic cells and sperm, have rapidly evolved across mammals. Ablation of multiple miR-506 family clusters compromises sperm competitiveness and male reproductive fitness, suggesting these miRNAs function to finetune gene expression during spermatogenesis to enhance sperm competition and male reproductive success.


Despite rapid evolution across eutherian mammals, the X-linked miR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes ( Slitrk2 and Fmr1 ) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked miR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernable defects, but simultaneous ablation of five clusters containing nineteen members of the miR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked miR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the miR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Significance Statement The X-linked miR-506 family has rapidly evolved in mammals, but their physiological significance remains elusive. Given their abundant and preferential expression in the testis and sperm, these X-linked miRNAs likely play a functional role in spermatogenesis and/or early embryonic development. However, the deletion of either individual miRNA genes or all of the five miRNA clusters encoding 38 mature miRNAs did not cause major fertility defects in mice. When these mutant males were subjected to conditions resembling polyandrous mating, the mutant sperm were much less competitive than the wild-type sperm, rendering the mutant males “functionally sub-fertile”. Our data suggest that the miR-506 family of miRNAs regulates sperm competition and the reproductive fitness of the male.

### Competing Interest Statement

The authors have declared no competing interest.

The Rapidly Evolving X-linked miR-506 Family Finetunes Spermatogenesis to Enhance Sperm Competition

rapid-evolution-of-the-x-linked-mir-506-family-enhances-sperm-competitiveness-and-male-reproductive-fitness


Rapid Evolution of the X-Linked miR-506 Family Enhances Sperm Competitiveness and Male Reproductive Fitness
