Season 1 - Episode 4

Transcript

Hello, welcome to mirroring medicine with Kodi and Isabel! Today we will be discussing the human reproductive system and how intricate and amazing this system is. We will be discussing the differentiation of sex during gestation. The development of this system and changes that come post post puberty. This podcast is meant to provide an overview and it is not comprehensive, we will be going over the tip of the iceberg in regards to this topic and we recommend the audience researching this topic even further.

We want to remind our audience that this podcast does not constitute medical advice. If you have any questions regarding your health and reproductive system please visit your primary care doctor, urologist or ob/gyns. Thank you for tuning in!

So how does this begin?

We will be starting off with the basics. Whether or not the sperm cell is carrying an x or y chromosome. At fertilization, the egg cell will fuse with the sperm cell. It's the sperm cell that determines whether or not the embryo will develop into a male or female.

The Y chromosome has a specific gene unique to it called the SRY gene (sex-determining region Y gene). For many decades this gene was seen as the sole predictor of the sex determination, however recent research suggests that  “gonadal determination has proven to rely on a complex network of genes” (Rey, 2020). Today we will only mention the SRY gene, as it is the most studied and understood pathway in regards to sexual determination. The SRY gene encodes for the testis-determining factor (TDF), which initiates male sex determination. Leading to the development of testes.

I want to define the key ducts that allow this process to be possible. The Mullerian and Wolffian ducts. The mullerian ducts will later form fallopian tubes, uterus and part of the vagina. Whereas the wolffian ducts become the epididymis, vas deferens and seminal vesicles. These ducts exist in both XX and XY embryos, the first signs of sex differentiation occur around week 6 post conception. Therefore up until this point both XX AND XY embryos can develop male or female genitalia. In male embryos, androgens and anti-Müllerian hormone (AMH) (Rey, 2020) will progress the development of the wolffian ducts and regress the mullerian ducts. The lack of androgens in what leads to the progression of mullerian ducts and regression of wolffian ducts. Although there are many known potential variations and syndromes that arise particularly from this crucial time in gestation we will save that for a future podcast. 

Female:

Another interesting aspect of the development of female reproduction systems is that eggs also known as oocytes are created in the womb.  The primary follicles will first be observed 15-16  weeks. Primary follicle is the earliest stage of follicle development, these cells are arrested in prophase I (khan academy, 2024). Graafian follicles appear at 23-24 weeks. Graffian follicles are the mature follicles which will remain in the same state until ovulation. By the end of the 7th month of gestation, mitotic activity has ceased and almost all germ cells have entered meiotic prophase. (Rey, 2020) 

Progression of egg count:

• At 25 weeks gestation the female fetus will have 6-7 million ovarian follicles. (Rey, 2020)

• At birth only 2 million remain

• Before puberty 10,000 immature eggs are lost monthly

• After puberty 1000 immature eggs are lost each month (Dr. Sherman Silber, 2024)

• The uterus is a very dynamic organ. It changes shape throughout a woman's life. 

• At birth 3.5 cm length, 1.4 cm width

• Prepuberty 2.5-4 cm width less can 1cm

• Puberty and adult 5-8 cm length, 1.5 cm  (banker, 2024)

• From the size of a lemon prepregnancy to the size of a watermelon during pregnancy (cleveland clinic, 2024), after 6 weeks it can return to the prepregnancy size, but will be slightly larger.

Menstrual cycle

• Avg 28 days

• Follicular (proliferative) phase (first day of menses to ovulation): during this phase the ovarian follicles are being developed. Categorized as a rise in serum estradiol parallel to growth of follicle size. This is also along with the increased number of granulosa cells, these are the cells that surround and support the oocyte. 

• As the follicular phase comes to an end there is a luteinizing hormone peak. 10-12 hours after this peak ovulation occurs. The beginning of the LH surge occurs roughly 34 to 36 hours prior to ovulation and is a relatively precise predictor for timing ovulation. During this phase 15-20 follicles are recruited and only one emerges as dominant (that will be the one that will be released). (reed, 2000)

• Ovulation 12-24 period. Egg is released from the ovary and then bright into the fallopian tube.  (mayo clinic 2024)

• Luteal (secretory) phase is approximately 14 days. During this time the corpus luteum forms from a ruptured follicle and subsequently degenerates. There is a rise of progesterone during this phase. 

This podcast was inspired by the many organizations that aim to bring reproductive education to all. Today we will highlight HealthConnected. This organization provides reproductive education to adolescents and young adults by fostering an open dialogue, providing evidence-based programs, and ensuring access to essential resources. This empowers young individuals to make informed decisions about their sexual health. This organization is california based and empowered young people with education. Please check out this organization and if you would like to donate we will provide the link below. 

Male:

What is the male reproductive system and what does it do? 

• The male reproductive system essentially produces sperm. This can produce, maintain, discharge, and transport semen and sperm. Whilst, also producing and secreting male sex hormones. The main hormones of this system are testosterone and androgens. 

• Mullarian/Wolfian duct differentiation via Y chromosome

• So for this Mullarian/Wolfian duct differentiation via the Y chromosome…Let’s look at the Jost Paradigm which is further validated from research conducted nowadays. Alfred Jost, elucidated that genetic factors that determine sex influence the fate of gonads (or sexual organs). Genetic factors, if in absence of the “maleness” genetic factor, the sexual organ differentiates into becoming an ovary. However, if there is a presence of a maleness factor, it can produce the testes as we know it. Then second differentiation occurs afterwards for the ovary and the testes. [3]

• This jost paradigm tells us about the Mullarian/Wolfian duct differentiation as this determines the composition of sex chromosomes subsequently determining the sex of the embryo. 

• The Y chromosome activates the molecular and cellular biology of somatic cells (Sertoli and Leydig) 

• Pathway of sperm- SEVEN UP

• Seminiferous Tubules - generates millions of sperm from spermatogonia that have undergone spermatogenesis. Primary spermatocyte (2n) → Secondary spermatocyte (n + n) → sperm cels (n + n + n + n) [4]

• Epididymis - Attatched to the testicles. Location where sperm finish maturing and is stored for use. They mature, store, transport, and protect sperm. [5] 

• Vas Deferens - Tube where it transports sperm out of the testes. [6]

• Ejaculatory Duct - Is formed with a vas deferens and a seminal vesicle to create and “pick up” prostatic fluid that adds to the semen. Functionally used for emptying urethra. [7]

• Urethra - So, there are two roles of the urethra for men. Usually, the urethra allows for urine transport to exit the body. This is coordinated through the brain → bladder muscle tightening → squeezing urine out of the bladder. Also, brain → sphincter muscle relaxation → urine exit bladder. [8] In the men, the urethra passes thru prostate to penis. It acts as an apparatus for semen to exit. 

• Penis - Carrying sperm outside of the body through the penis. 

• Sperm count at ejaculation- things that decrease sperm count. So we know that sperm is made in the testes aka testicles, in which they mix with semen. Here are a couple medical contributors that can decrease low sperm count within semen. There could be swelling of the veins draining the testicle aka varicocele, infection, ejaculation problems, tumors, hormone level imbalance, genetic conditions, certain medications, prior surgeries, metals, x-ray use, drug & alcohol use, tobacco use, stress, & obesity. [15]

• Viagra - Helps treat erectile disfunction by increasing the amount of blood flow to your penis allowing it to maintain erection. 

• PreP (pre-exposure prophylaxis) - Helps prevent HIV infection for high risk individuals, have had anal sex, or not consistently used  a condom according to HIV.gov. [16]

• Sexual Dysfunction - According to the cleveland clinic as any problem that prevents a person or couple from experiencing satisfaction from sexual activity. [17]

• Ejactulatory duct obstruction: 

• Ducts are blocked - complete/classic EDO

• Blockage in one or partial in both - incomplete/partial EDO

• Similar to complete, no blockage - Functional EDO

Treatments: According to the mayo clinic a Vascectomy - prevents pregnancy by cutting the supply of sperm to semen, sealing the tubes that carry sperm. It is reversable and is 100% effective in preventing pregnancies. Low risk, far less costly than long-term birth control medications, less birth control steps. [18]

Finally, to summarize this podcast on reproductive pathways and sex, we have introduced a myriad of different systems including the female reproductive system, the process of a period, the male reproductive system, and mullarian/wolfian duct differentiation system. In this, we have also discussed different reproductive disorders including things that decrease sperm count etc. This serves as the foundation of reproduction and gestation and we recommend that you go explore more within this topic in medicine with this information in mind. 

Citations

1. Rey R, Josso N, Racine C. Sexual Differentiation. [Updated 2020 May 27]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: ⁠https://www.ncbi.nlm.nih.gov/books/NBK279001/⁠

2. Cleveland Clinic. “Uterus.” Cleveland Clinic, 17 May 2023,⁠ https://my.clevelandclinic.org/health/body/22467-uterus⁠. 

3. Blecher, Stan R, and Robert P Erickson. “Genetics of sexual development: a new paradigm.” American journal of medical genetics. Part A vol. 143A,24 (2007): 3054-68. doi:10.1002/ajmg.a.32037

4. Baiping Mao, Tiao Bu, Dolores Mruk, Chao Li, Fei Sun, C. Yan Cheng, Modulating the Blood–Testis Barrier Towards Increasing Drug Delivery, Trends in Pharmacological Sciences, Volume 41, Issue 10, 2020, Pages 690-700, ISSN 0165-6147, ⁠https://doi.org/10.1016/j.tips.2020.07.002⁠. (https://www.sciencedirect.com/science/article/pii/S0165614720301644)

5. “Epididymis.” NCI Dictionary of Cancer Terms, National Cancer Institute,⁠ www.cancer.gov/publications/dictionaries/cancer-terms/def/epididymis⁠. 

6. National Cancer Institute. "Definition of Vas Deferens." NCI Dictionary of Cancer Terms, National Cancer Institute, ⁠www.cancer.gov/publications/dictionaries/cancer-terms/def/vas-deferens⁠. 

7. Cleveland Clinic. "Ejaculatory Duct Obstruction." Cleveland Clinic, my.clevelandclinic.org/health/diseases/22819-ejaculatory-duct-obstruction. 

8. Johns Hopkins Medicine. "Anatomy of the Urinary System." Johns Hopkins Medicine, ⁠www.hopkinsmedicine.org/health/wellness-and-prevention/anatomy-of-the-urinary-system⁠. 

9. The Center for Male and Female Infertility. "Beating the Biological Clock." The Center for Male and Female Infertility, ⁠www.infertile.com/infertility-101/female-infertility/beating-biological/⁠. 

10. Banker H, Cohen HL, Sandhu PK. Sonography Pediatric Gynecology Assessment, Protocols, and Interpretation. [Updated 2023 Jan 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: ⁠https://www.ncbi.nlm.nih.gov/books/NBK570595/⁠

11. Holesh JE, Bass AN, Lord M. Physiology, Ovulation. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: ⁠https://www.ncbi.nlm.nih.gov/books/NBK441996/⁠

12. Mayo Clinic Staff. "What Are the Signs of Ovulation?" Mayo Clinic, ⁠www.mayoclinic.org/healthy-lifestyle/getting-pregnant/expert-answers/ovulation-signs/faq-20058000⁠. 

13. Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. [Updated 2018 Aug 5]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: ⁠https://www.ncbi.nlm.nih.gov/books/NBK279054/⁠

14. Khan Academy. "Oogenesis and Follicular Development Review." Khan Academy, ⁠www.khanacademy.org/science/how-does-the-human-body-work-class-12/x7babbc170453fdb8:human-reproduction/x7babbc170453fdb8:gametogenesis/a/oogenesis-and-follicular-development-review⁠. 

15. Mayo Clinic Staff. "Low Sperm Count." Mayo Clinic, ⁠www.mayoclinic.org/diseases-conditions/low-sperm-count/symptoms-causes/syc-20374585⁠. 

16. U.S. Department of Health and Human Services. "Pre-Exposure Prophylaxis (PrEP)." HIV.gov, ⁠www.hiv.gov/hiv-basics/hiv-prevention/using-hiv-medication-to-reduce-risk/pre-exposure-prophylaxis⁠. 

17. Cleveland Clinic. "Sexual Dysfunction." Cleveland Clinic, my.clevelandclinic.org/health/diseases/9121-sexual-dysfunction. 

18. Mayo Clinic Staff. "Vasectomy." Mayo Clinic, ⁠www.mayoclinic.org/tests-procedures/vasectomy/about/pac-20384580⁠.