Fshb, the gene encoding the beta subunit of follicle-stimulating hormone (FSH), is crucial for fertility. FSH is involved in regulating oocyte maturation, ovulation, and hormone synthesis in females, and spermatogenesis in males. Its transcription is regulated by GnRH and activin, with activin signaling through SMAD transcription factors [3,5,6].

The Fshb knockout mouse model, first reported in 1997, has been valuable for physiological and genetic studies in reproductive and skeletal biology. It has helped delineate the extragonadal roles of FSH in bone cells, opening up research avenues in osteoporosis and adiposity in postmenopausal women. Since 2009, studies using this model have explored FSH rerouting in vivo, the role of N-glycosylation on FSHβ, and FSH's roles in somatic-germ cell interactions in gonads [1].

In human studies, the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism has been associated with idiopathic infertility in men, as different genotypes show distinct distributions in bi-testicular volume, FSH levels, and may contribute to the genetic factors of infertility [2]. In Brazilian women, the T allele of rs10835638 is associated with the development of minimal/mild endometriosis [4]. In Danish men from the general population, the FSHB-211G>T polymorphism affects serum FSH levels and calculated free testosterone/LH ratio, and is associated with smaller testis size, though it has only a minor modulating influence on testis size and function in healthy men [7]. In infertile patients, the FSHB c.-211G>T polymorphism does not affect Sertoli cell numbers or workload, suggesting the previously observed clinical phenotype might be due to hypo-stimulated spermatogenesis rather than decreased Sertoli cell number [8].

In conclusion, Fshb is essential for fertility-related processes and has implications in various reproductive-related diseases. The Fshb knockout mouse model has significantly contributed to understanding its functions in reproductive and skeletal biology, and human genetic studies on FSHB polymorphisms have provided insights into idiopathic infertility and endometriosis.

References:

1. Kumar, T Rajendra. . Fshb Knockout Mouse Model, Two Decades Later and Into the Future. In Endocrinology, 159, 1941-1949. doi:10.1210/en.2018-00072. https://pubmed.ncbi.nlm.nih.gov/29579177/

2. Krenz, Henrike, Sansone, Andrea, Kliesch, Sabine, Gromoll, Joerg, Schubert, Maria. 2021. FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility. In Frontiers in endocrinology, 12, 780403. doi:10.3389/fendo.2021.780403. https://pubmed.ncbi.nlm.nih.gov/34992580/

3. Bohaczuk, Stephanie C, Cassin, Jessica, Slaiwa, Theresa I, Thackray, Varykina G, Mellon, Pamela L. . Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB. In Endocrinology, 162, . doi:10.1210/endocr/bqab069. https://pubmed.ncbi.nlm.nih.gov/33824966/

4. Bianco, Bianca, Loureiro, Flávia Altheman, Trevisan, Camila Martins, Laganà, Antonio Simone, Barbosa, Caio Parente. 2023. Implication of FSHB rs10835638 variant in endometriosis in Brazilian women. In Einstein (Sao Paulo, Brazil), 21, eAO0483. doi:10.31744/einstein_journal/2023AO0483. https://pubmed.ncbi.nlm.nih.gov/37909652/

5. Bohaczuk, Stephanie C, Thackray, Varykina G, Shen, Jia, Skowronska-Krawczyk, Dorota, Mellon, Pamela L. . FSHB  Transcription is Regulated by a Novel 5' Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism. In Endocrinology, 162, . doi:10.1210/endocr/bqaa181. https://pubmed.ncbi.nlm.nih.gov/33009549/

6. Schang, Gauthier, Toufaily, Chirine, Bernard, Daniel J. . HDAC inhibitors impair Fshb subunit expression in murine gonadotrope cells. In Journal of molecular endocrinology, 62, 67-78. doi:10.1530/JME-18-0145. https://pubmed.ncbi.nlm.nih.gov/30481159/

7. Bang, Anne Kirstine, Almstrup, Kristian, Nordkap, Loa, Rajpert-De Meyts, Ewa, Jørgensen, Niels. 2020. FSHB and FSHR gene variants exert mild modulatory effect on reproductive hormone levels and testis size but not on semen quality: A study of 2020 men from the general Danish population. In Andrology, 9, 618-631. doi:10.1111/andr.12949. https://pubmed.ncbi.nlm.nih.gov/33236519/

8. Schubert, Maria, Kaldewey, Sophie, Pérez Lanuza, Lina, Wistuba, Joachim, Gromoll, Jörg. 2020. Does the FSHB c.-211G>T polymorphism impact Sertoli cell number and the spermatogenic potential in infertile patients? In Andrology, 8, 1030-1037. doi:10.1111/andr.12777. https://pubmed.ncbi.nlm.nih.gov/32096339/