In mammals, spermatogenesis is maintained throughout life by a small subpopulation of type A spermatogonia called spermatogonial stem cells (SSCs). In rodents, SSCs, or Asingle spermatogonia, form the self-renewing population. SSCs can also divide into Apaired (Apr) spermatogonia that are predestined to differentiate. Apaired spermatogonia produce chains of Aaligned (Aal) spermatogonia that divide to form A1 to A4, then type B spermatogonia. Type B spermatogonia will divide into primary spermatocytes that undergo meiosis. In human, there are only two different types of A spermatogonia, the Adark and Apale spermatogonia. The Adark spermatogonia are considered reserve stem cells, whereas the Apale spermatogonia are the self-renewing stem cells. There is only one generation of type B spermatogonia before differentiation into spermatocytes, which makes human spermatogenesis less efficient than in rodents. Although the biology of human SSCs is not well known, a panel of phenotypic markers has recently emerged that is remarkably similar to the list of markers expressed in mice. One such marker, the orphan receptor GPR125, is a plasma membrane protein that can be used to isolate human SSCs. Human SSCs proliferate in culture in response to growth factors such as GDNF, which is essential for SSC self-renewal in mice and triggers the same signaling pathways in both species. Therefore, despite differences in the spermatogonial differentiation scheme, both species use the same genes and proteins to maintain the pool of self-renewing SSCs within their niche. Spermatocytic seminomas are mainly found in the testes of older men, and they rarely metastasize. It is believed that these tumors originate from a postnatal germ cell. Because these lesions can express markers specific for meiotic prophase, they might originate form a primary spermatocyte. However, morphological appearance and overall immunohistochemical profile of these tumors indicate that the cell of origin could also be a spermatogonial stem cell.

Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) regulates the concentration of all–trans retinoic acid (RA) and plays a key role in germ cell differentiation by controlling local distribution of RA. The mechanisms regulating Cyp26b1 expression in postnatal Sertoli cells, the main components of the stem cell niche, are so far unknown. During gonad development, expression of Cyp26b1 is maintained by Steroidogenic Factor 1 (SF‐1) and Sex‐Determining Region Y. Box‐9 (SOX9), which ensure that RA is degraded and germ cell differentiation is blocked. Here, we show that the NOTCH target Hairy/Enhancer‐of‐Split Related with YRPW Motif 1 (HEY1), a transcriptional repressor, regulates germ cell differentiation via direct binding to the Cyp26b1 promoter and thus inhibits its expression in Sertoli cells. Further, using in vivo germ cell ablation, we demonstrate that undifferentiated type A spermatogonia are the cells that activate NOTCH signaling in Sertoli cells through their expression of the NOTCH ligand JAGGED‐1 (JAG1) at stage VIII of the seminiferous epithelium cycle, therefore mediating germ cell differentiation by a ligand concentration‐dependent process. These data therefore provide more insights into the mechanisms of germ cell differentiation after birth and potentially explain the spatiotemporal RA pulses driving the transition between undifferentiated to differentiating spermatogonia.—Parekh, P. A., Garcia, T. X., Waheeb, R., Jain, V., Gandhi, P., Meistrich, M. L., Shetty, G., Hofmann, M.‐C. Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation. FASEB J. 33, 8423–8435 (2019). http://www.fasebj.org

This study was conducted to investigate the toxic effects of di (n-butyl) phthalate (DBP) on reproductive functions in male rabbits and the probable protective role of ginger. Twenty rabbits were divided equally into 4 groups: control group; DBP group (520 mg/kg body weight [BW] DBP orally), DBP+ginger group (520 mg/kg BW DBP and 400 mg/kg BW ginger) and ginger group (400 mg/kg BW ginger orally). Treatments were given three-times/week. After 7 wk of the experiment, DBP induced significant reduction in testis and prostate weights, serum and intratesticular testosterone concentrations, sperm counts both mass and progressive sperm motility and live sperms percentage as well as significant elevation of testicular malondialdehyde compared to control group. No significant changes were detected in epididymal weights, serum FSH and serum LH concentrations and testicular total superoxide dismutase and glutathione peroxidase activities in all treated groups. DBP induced considerable histopathological alterations in testis and to minimal extent in epididymis and prostates. Ginger treatment attenuated the significant changes to a certain extent induced by DBP intoxication in male rabbits probably due to its potential to scavenge free radicals.

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Key words:estrus synchronization, progestagen sponge, PGF2α, ewes, breeding season This study was conducted to evaluate reproductive performance of Barki ewes subjected to three estrus synchronization programs in field conditions during breeding season. For this purpose, 36 cycling ewes were divided into 4 groups according to the program assigned: Group SeCG (n=10): received intravaginal progesterone sponge (40 mg Fluorogestone acetate, Chrono-gest®, Intervet International) for 7 days, at time of sponge removal, each ewe received i.m injection of 500 IU eCG (Folligon®, Intervet International); Group PG-PG (n=10): received double injections of 250μg Cloprostenol (PGF2α analogue, Estrumate®, Intervet International) 11 days apart; Group GPG (n=6): received 4μg Buserelin by i.m injection on day 0 (GnRH analogue-Receptal®, Intervet International), on day 5 animals received 250μg Cloprostenol followed by 4μg Buserelin by i.m injection on day 7; Group C (n=10): served as control group that did not receive any treatment. Results showed that estrus induction rate was significantly high in SeCG group that was recorded at 100% (P<0.05), while it was 90%, 60%, and 50% for PG-PG, C and GPG respectively. Estrus synchrony was more uniform in SeCG group as 70% of ewes exhibited estrus around 24-36 hrs from end of treatment. There was no significant difference among groups in pregnancy and lambing rate (p>0.05). Pregnancy rates were 100%, 90%, 88.9%, and 83.3% for GPG, SeCG, PG-PG, and C group respectively. Conclusion, from results we conclude that intravaginal progesterone sponge for 7 days+500IU eCG at sponge removal is convenient for estrus synchronization of ewes raised in field conditions during breeding season. Moreover, reproductive and fertility parameters recorded in the current study are acceptable and within values reported previously in farm conditions.

Key words: cystic follicles, estrus, GnRH, PGF2α, Potassium iodide.Cystic ovarian follicles "COF" is a common ovarian disorder diagnosed in dairy cattle that cause significant economic losses in dairy industry. This study was designed to evaluate efficacy of different therapeutic protocols of COF without determining cyst type. The study was conducted on 104 Holstein-Friesian cystic cows that were divided randomly to the following treatments: Experiment Ι: 1) Group G, n=27, subdivided into A) n=13: treated with 20μg Buserelin-GnRH agonist and B) n=14: treated with 100μg GonadorelinGnRH agonist; 2) Group GP, n=23: received 20μg Buserelin on day 0-500μg of PGF2α on day 10; 3) Group GGP, n=27: received 2 doses of 20μg Buserelin 7 ds apart followed by 500μg PGF2α 7ds from the 2 nd Buserelin injection; 4) Group GPG (Ovsynch), n=17: received 20μg Buserelin on day 0-500μg PGF2α on day 7, and 48hrs later, 20μg Buserelin was injected; 5) Group C, n=10: no treatment received. 22 normal cycling cows were kept as a normal control-NC. Experiment ΙΙ: This part of the study was conducted on 34 cystic animals that did not respond to one of the previous treatments in experiment Ι and were divided into 2 groups: 1) Group CGP, n=19: CIDR+100μg Gonadorelin-(d 0), then 500μg of PGF2α on day 7, insert was removed on day 9; 2) Group PI, n=15: treated by oral administration of 5gm Potassium iodide dissolved in 500 ml sterile water for 7 successive days. Treated Cows were observed for 35 days from the end of treatment, females exhibited estrus were inseminated within 12 hours of detected heat. Pregnancy was confirmed by per rectum on day 50 post-insemination. Results showed that GP protocol achieved highest (P<0.05) estrus induction rate (EIR) recorded at 87%, followed by 70% for G and GGP group, and lowest (53%) obtained in GPG treated cows. Conception rate at 1 st estrus and total conception rate (3 cycles after treatment) did not differ significantly among treatment groups, while pregnancy rates (PR) were significantly different (P<0.05) with highest (65.21%) obtained in GP protocol. Other groups recorded 63%, 55.55%, and 41.17% PR for G, GGP, and GPG respectively. In experiment ΙΙ, EIR was 47.36% and 33.33% for CGP and PI respectively with no significant difference, all conceived after 3 estrous cycles by the end of the experiment. In conclusion, GnRH+ PGF2α 10ds later was the most suitable treatment of COF regardless of cyst type, GGP protocol might be a profitable alternative to Ovsynch for treatment of cystic ovaries. Persistent cases of COF could be recruited to avoid culling for other treatment options such as CIDR or Potassium iodide with equal therapeutic efficacy.Correspondence to: rwaheeb@alexu.edu.eg.